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DE19633206C2 - Steroid compounds with an antimicrobial effect - Google Patents

Steroid compounds with an antimicrobial effect

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Publication number
DE19633206C2
DE19633206C2 DE1996133206 DE19633206A DE19633206C2 DE 19633206 C2 DE19633206 C2 DE 19633206C2 DE 1996133206 DE1996133206 DE 1996133206 DE 19633206 A DE19633206 A DE 19633206A DE 19633206 C2 DE19633206 C2 DE 19633206C2
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Germany
Prior art keywords
estra
hydroxy
methoxy
triene
nmr
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
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DE1996133206
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German (de)
Other versions
DE19633206A1 (en
Inventor
Bruno Schoenecker
Ralf Wyrwa
Ute Moellmann
Reimar Krieg
Manuela Dubs
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Friedrich Schiller Universtaet Jena FSU
Leibniz Institut fuer Naturstoff Forschung und Infektionsbiol eVi
Original Assignee
Friedrich Schiller Universtaet Jena FSU
Leibniz Institut fuer Naturstoff Forschung und Infektionsbiol eVi
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Priority to DE1996133206 priority Critical patent/DE19633206C2/en
Publication of DE19633206A1 publication Critical patent/DE19633206A1/en
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Publication of DE19633206C2 publication Critical patent/DE19633206C2/en
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
    • C07J41/0011—Unsubstituted amino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
    • C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
    • C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07J—STEROIDS
    • C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
    • C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Steroid Compounds (AREA)

Description

Die Erfindung betrifft Steroidverbindungen mit antimikrobieller Wirkung, insbesondere zur Anwendung in der pharmazeutischen Forschung, Industrie und Landwirtschaft.The invention relates to steroid compounds with an antimicrobial effect, especially for use in pharmaceutical research, industry and agriculture.

Es ist bekannt, daß weltweit Infektionen mit bakteriellen Krankheitserregern zunehmen, deren Therapie durch Resistenzentwicklung erschwert oder nicht mehr möglich ist. Zu diesen Problemkeimen zählen gegen Methicillin resistente Staphylococcen (MRSA) [M. Kresken, Bundesgesundheitsblatt 38, 1996, 170-178], glycopeptidresistente Enterococcen [A. P. Johnson et all., Resistance to vancomycin and teicoplanin: an emerging clinical problem. Clin. Microbiol. Rev. 3, 1990, 280-291] und Mycobakterien [B. R. Bloom, J. L. Murray, Tuberculosis: commentary on a Reemergent Killer. Science 257, 1992, 1055-1064]. Verbunden mit dem dramatischen Anstieg von Tuberkuloseerkrankungen rufen Mycobakterien 3 Millionen Todesfälle jährlich hervor. Die Zahl resistenter Mycobakterien nimmt bedrohlich zu. Zur Bekämpfung dieser Krankheiten besteht ein dringender Bedarf an neuen Wirkstoffen und Wirkprinzipien, insbesondere zur Entgegenwirkung von Antibiotikaresistenz sowie zur Bekämpfung bakterieller Infektionen bei Unverträglichkeiten gegenüber gebräuchlichen Antibiotika als Alternative zu Chemotherapeutika.It is known that infections with bacterial pathogens worldwide increase, the therapy of which complicates resistance development or not is more possible. These problem germs include against methicillin resistant staphylococci (MRSA) [M. Kresques, Federal Health Gazette 38, 1996, 170-178], glycopeptide-resistant enterococci [A. P. Johnson et all., Resistance to vancomycin and teicoplanin: an emerging clinical problem. Clin. Microbiol. Rev. 3, 1990, 280-291] and mycobacteria [B. R. Bloom, J. L. Murray, Tuberculosis: commentary on a Reemergent Killer. Science 257, 1992, 1055-1064]. Associated with the dramatic increase in Tuberculosis diseases cause mycobacteria 3 million deaths annually. The number of resistant mycobacteria is threateningly increasing. For There is an urgent need for new ones to combat these diseases Active substances and active principles, in particular to counteract Antibiotic resistance and to fight bacterial infections Intolerance to common antibiotics as an alternative to Chemotherapy drugs.

Im Vordergrund bereits bekannter und in der Literatur beschriebener primärer Steroidamine standen hormonelle Wirkungen dieser Substanzen [D. E. Evans and G. H. R. Summers, J. Chem. Soc., 1956, 4821-24; H. B. Henbest and W. R. Jackson, J. Chem. Soc., 1962, 954-9; B. Schönecker und K. Ponsold, Tetrahedron, 1975, 31, 1113-18; A. M. Bellini, E. Mencini, M. P. Quaglio, M. Guarneri, A. Fini, Steroids, 56, 1991, 395-8] oder Untersuchungen zur optischen Rotationsdispersion und zum Circulardichroismus [H. Ripperger, K. Schreiber, G. Snatzke und K. Ponsold, Tetrahedron, 25, 1969, 827-36]. Über baktericide und fungicide Wirkungen sind bisher nur wenige Ergebnisse bekannt geworden [J. J. Kabara, D. L. Holzschu, P. Demokritos Catsoulacos, Lipids, 11, 1976, 755-62; A. M. Bellini, E. Mencini, M. P. Quaglio, M. Guarneri, A. Fini, Arch. Pharm., 323, 1990, 201-5; A. M. Bellini, M. P. Quaglio, E. Mencini, M. Guarneri, G. Cavazzini, A. Fini, Arch. Pharm, 322, 1989, 879-83; E. R. Dolle, H. S. Allaudeen, I. L. Kruse, J. Med. Chem., 33, 1990, 877-80; K. Prehn, L. Tybring, J. Forchhammer, Acta Pathol. Microbiol. Scand., 71, 1967, 135-40].In the foreground the primary known and described in the literature Steroidamines were hormonal effects of these substances [D. E. Evans and G.H.R. Summers, J. Chem. Soc., 1956, 4821-24; H. B. Henbest and  W. R. Jackson, J. Chem. Soc., 1962, 954-9; B. Schönecker and K. Ponsold, Tetrahedron, 1975, 31, 1113-18; A.M. Bellini, E. Mencini, M.P. Quaglio, M. Guarneri, A. Fini, Steroids, 56, 1991, 395-8] or studies on optical rotation dispersion and circular dichroism [H. Ripperger, K. Schreiber, G. Snatzke and K. Ponsold, Tetrahedron, 25, 1969, 827-36]. So far there are only a few bactericidal and fungicidal effects Results made known [J. J. Kabara, D.L. Holzschu, P. Demokritos Catsoulacos, Lipids, 11, 1976, 755-62; A.M. Bellini, E. Mencini, M.P. Quaglio, M. Guarneri, A. Fini, Arch. Pharm., 323, 1990, 201-5; AT THE. Bellini, M.P. Quaglio, E. Mencini, M. Guarneri, G. Cavazzini, A. Fini, Arch. Pharm, 322, 1989, 879-83; E. R. Dolle, H. S. Allaudeen, I. L. Kruse, J. Med. Chem., 33, 1990, 877-80; K. Prehn, L. Tybring, J. Forchhammer, Acta Pathol. Microbiol. Scand., 71, 1967, 135-40].

Insgesamt muß eingeschätzt werden, daß bekannte Steroidamine keine hinreichende Wirksamkeit bezüglich der Breite des antimikrobiellen Spektrums aufweisen. So sind keine Aktivitäten gegen multiresistente Staphylococcen und glycopeptidresistente Enterococcen erfaßt und zum Teil auch keine Aktivitäten gegen Mycobakterien nachgewiesen.Overall, it must be estimated that known steroid amines do not sufficient effectiveness with regard to the breadth of the antimicrobial Show spectrum. So there are no activities against multi-resistant Staphylococci and glycopeptide-resistant enterococci recorded and in part no activity against mycobacteria was detected.

Der Erfindung liegt deshalb die Aufgabe zugrunde, geeignete Verbindungen zu schaffen, die eine hohe antibakterielle und fungicide Wirksamkeit in einem breiten Spektrum besitzen, die eine effektive Bekämpfung von Antibiotikaresistenz bei bakteriellen Infektionen ermöglichen und die besser verträglich sowie einfacher herstellbar sind als bisherige Verbindungen.The invention is therefore based on the object of suitable connections to create a high antibacterial and fungicidal effectiveness in possess a wide range that effectively combat Antibiotic resistance in bacterial infections enable and better are compatible and easier to manufacture than previous connections.

Die Aufgabe wird erfindungsgemäß durch neue Steroidaminderivate, bei denen durch geeignete Reaktionen Azomethine, sekundäre und tertiäre Amine sowie Ammoniumsalze als Strukturelemente fungieren, gelöst. The object is achieved by new steroidamine derivatives those by suitable reactions azomethines, secondary and tertiary Amines and ammonium salts act as structural elements, dissolved.  

Vergleiche mit Antibiotika, wie Ciproflaxacin, Rifampicin oder dem synthetischen Isonictinsäurehydrazid (INH) zeigen äquivalente antibakterielle Aktivität mit weitaus breiterem Wirkungsspektrum. Insbesondere ergeben sich neue Wirkmechanismen auf Bakterienzellen, wodurch eine bessere Bekämpfung einer Antibiotikaresistenz bei bakteriellen Infektionen ermöglicht wird.Compare with antibiotics like ciproflaxacin, rifampicin or that synthetic isonictic acid hydrazide (INH) show equivalents antibacterial activity with a much broader spectrum of activity. In particular, there are new mechanisms of action on bacterial cells, thereby better fighting antibiotic resistance in bacterial Infections.

Die Erfindung betrifft Estratrienderivate der allgemeinen Formel I
The invention relates to estratriene derivatives of the general formula I.

worin
R1 und R2 ein Wasserstoffatom oder eine Hydroxygruppe,
R3 oder R4 die Gruppen
wherein
R 1 and R 2 represent a hydrogen atom or a hydroxy group,
R 3 or R 4 the groups

und das Symbol die α- oder β-Stellung bedeuten.and the symbol means the α or β position.

Außerdem betrifft die Erfindung Cholestanderivate der allgemeinen Formel II
The invention also relates to cholestane derivatives of the general formula II

worin
R5 ein Wasserstoffatom oder eine Hydroxygruppe,
R6 die Gruppen
wherein
R 5 represents a hydrogen atom or a hydroxy group,
R 6 the groups

und das Symbol and the symbol

die α- oder β-Stellung bedeuten. mean the α or β position.

Die erfindungsgemäßen Verbindungen werden zum Beispiel hergestellt, indem in bekannter Weise
The compounds of the invention are prepared, for example, in a known manner

  • a) Steroidamine in einem geeigneten Lösungsmittel, wie wasserfreies Methanol, bei Raumtemperatur mit entsprechenden Aldehyden oder Ketonen zu Azomethinen umgesetzt werden;a) Steroid amines in a suitable solvent, such as anhydrous Methanol, at room temperature with the corresponding aldehydes or ketones be converted to azomethines;
  • b) primäre und sekundäre Steroidamine in einem geeigneten Lösungsmittel, wie Methanol und einem Katalysator, wie Essigsäure, bei Reaktions­ temperaturen von 70-80°C mit Vinylverbindungen, wie Vinylpyridin, zu entsprechenden Mono- und Di-(pyridylethyl)aminosteroiden umgesetzt werden;b) primary and secondary steroid amines in a suitable solvent, such as methanol and a catalyst such as acetic acid upon reaction  temperatures of 70-80 ° C with vinyl compounds such as vinyl pyridine corresponding mono- and di- (pyridylethyl) aminosteroids implemented become;
  • c) Azomethine, wie unter a) dargestellt, mit NaBH4 oder anderen gebräuchlichen Reduktionsmitteln in geeigneten Lösungsmitteln, wie wasserfreies Methanol, bei Raumtemperatur zu den entsprechenden Aminen reduziert werden;c) Azomethines, as shown under a), are reduced with NaBH 4 or other customary reducing agents in suitable solvents, such as anhydrous methanol, to the corresponding amines at room temperature;
  • d) sekundäre und tertiäre Amine, wie unter b), c), d) beschrieben mit Ammoniumsalzen, wie NH4Cl, Alkylhalogeniden, wie Methyljodid, oder organischen Säuren, wie Essigsäure, in geeigneten Lösungsmitteln, wie Methanol, bei Raumtemperatur zu den entsprechenden Ammoniumsalzen umgesetzt werden;d) secondary and tertiary amines, as described under b), c), d) with ammonium salts, such as NH 4 Cl, alkyl halides, such as methyl iodide, or organic acids, such as acetic acid, in suitable solvents, such as methanol, at room temperature to give the corresponding Ammonium salts are implemented;
  • e) sekundäre Amine, wie unter b), c), d) beschrieben, mit Alkyl- oder Arylhalogeniden in geeigneten Lösungsmitteln, wie Methylenchlorid, in Gegenwart von Kaliumcarbonat oder anderen Basen zu den entsprechenden tertiären Aminen umgesetzt werden;e) secondary amines, as described under b), c), d), with alkyl or Aryl halides in suitable solvents, such as methylene chloride, in Presence of potassium carbonate or other bases to the corresponding tertiary amines are implemented;
  • f) sekundäre Amine, wie unter b), c), d) beschrieben, mit Acetanhydrid oder mit anderen gebräuchlichen Acylierungsmitteln in Pyridin oder in Gegenwart anderer Basen bei Raumtemperatur zu den entsprechenden Acylamiden umgesetzt werden.f) secondary amines, as described under b), c), d), with acetic anhydride or with other common acylating agents in pyridine or in the presence other bases at room temperature to the corresponding acylamides be implemented.

Die erfindungsgemäßen Verbindungen zeigen breite antimikrobielle Aktivität gegen grampositive und gramnegative Bakterien, insbesondere auch gegen multiresistente Staphylococcen, glycopeptidresistente Enterococcen und Mycobakterien, sowie gegen Pilze.The compounds according to the invention show broad antimicrobial activity against gram-positive and gram-negative bacteria, in particular also against multi-resistant staphylococci, glycopeptide-resistant enterococci and Mycobacteria, as well as against fungi.

Zum Nachweis der antimikrobiellen Aktivität wurde ein standardisierter Agardiffusionsplattentest mit folgenden Testorganismen durchgeführt:A standardized was used to demonstrate the antimicrobial activity Agar diffusion plate test carried out with the following test organisms:

Bacillus subtilis ATCC 6633, Micrococcus flavus ATCC 10240, Staphylococcus aureus 134/94 (MRSA), Enterococcus faecalis 1528 (glycopeptidresistend), Escherichia coli AS19, Mycobakterium smegmatis SG 987, M. fortuitum B., M. chelonae B., Glomerella cingulata.Bacillus subtilis ATCC 6633, Micrococcus flavus ATCC 10240, Staphylococcus aureus 134/94 (MRSA), Enterococcus faecalis 1528  (glycopeptide resistant), Escherichia coli AS19, Mycobacterium smegmatis SG 987, M. fortuitum B., M. chelonae B., Glomerella cingulata.

Die Ergebnisse der Testung sind in Tabellen 1-3 zusammengefaßt. Vor allem die Ferrocenylamino-, Ferrocenylimino- und (Pyridylethyl) aminosteroide erfassen in ihrem Wirkungsspektrum eine Breite von Mikroorganismen, die weit über das Wirkungsspektrum der Vergleichssubstanzen Ciprofloxacin, Rifampicin und INH hinausgehen. Von besonderem Interesse ist die Aktivität gegen MRSA und Mycobakterien.The results of the testing are summarized in Tables 1-3. Especially the ferrocenylamino, ferrocenylimino and (pyridylethyl) aminosteroids cover a wide range of microorganisms in their spectrum of activity far beyond the spectrum of action of the comparison substances ciprofloxacin, Get Rifampicin and INH. The activity is of particular interest against MRSA and mycobacteria.

Von ausgewählten Verbindungen wurden die minimalen Hemmkonzentratio­ nen (MHK) bei verschiedenen Mycobakterienspezies in einem Mikro­ dilutionstest bestimmt. Folgende Stämme wurden verwendet:The minimal inhibitory concentration of selected compounds was determined NEN (MIC) in different mycobacterial species in one micro dilution test determined. The following strains were used:

Mycobakterium smegmatis SG 987, M. fortuitum B., M. chelonae B., M. vaccae IMET 10670, M. aurum SB66.Mycobacterium smegmatis SG 987, M. fortuitum B., M. chelonae B., M. vaccae IMET 10670, M. aurum SB66.

Die Ergebnisse sind in Tabelle 4 angegeben. Die geprüften Substanzen sind gegen alle eingesetzten Mycobakterienspezies aktiv und zeigen damit ein breiteres Wirkungsspektrum als die parallel geprüften Therapeutika Ciprofloxacin, Rifampicin und INH, die gegen einige der verwendeten Stämme unwirksam sind.The results are shown in Table 4. The substances tested are active against all mycobacterial species used and thus show broader spectrum of activity than the therapeutics tested in parallel Ciprofloxacin, Rifampicin, and INH that are used against some of the Strains are ineffective.

Die erfindungsgemäßen Verbindungen eignen sich auf Grund ihrer anti­ mikrobiellen Wirksamkeit zur potentiellen Anwendung als Arzneimittel gegen bakterielle Infektionen bei Menschen und Nutztieren. Auch sind sie Leitstrukturen für die Herstellung antifungaler Wirkstoffe.The compounds according to the invention are suitable on the basis of their anti microbial activity for potential use as a pharmaceutical against bacterial infections in humans and farm animals. They are too Lead structures for the production of antifungal agents.

Die Verbindungen können außerdem entweder allein oder in Kombination mit anderen Wirkstoffen, wie z. B. β-Lactamen, Aminoglycosiden, Tetracyclinen, Macroliden, Tuberkulotika oder Azolen (Fungistatika) zur Potenzierung der Aktivität dieser Verbindungen verwendet werden, wodurch eine Verringerung von Nebenwirkungen durch Herabsetzung der einzusetzenden Dosen erreicht wird. The compounds can also be used either alone or in combination with other active ingredients, such as. B. β-lactams, aminoglycosides, Tetracyclines, macrolides, tuberculotics or azoles (fungistats) for Potentiating the activity of these compounds can be used a reduction in side effects by reducing the doses to be used is reached.  

Bei den genannten Erkrankungen können die Verbindungen entweder allein oder in Form von pharmazeutischen Präparaten mit physiologisch verträglichen, aus dem Stand der Technik bekannten Hilfs- und Trägerstoffen angewandt werden, wobei prinzipiell alle üblichen pharmakologischen Anwendungsformen, wie orale oder parenterale Applikation, möglich sind.In the diseases mentioned, the compounds can either be used alone or in the form of pharmaceutical preparations with physiological compatible auxiliary agents and carriers known from the prior art are used, in principle all the usual pharmacological Application forms, such as oral or parenteral administration, are possible.

Die Erfindung soll nachstehend anhand von 30 Substanzen als Ausführungs­ beispiele nach allgemeinen Vorschriften a) bis f), einschließlich der Test­ ergebnisse in Tabellen 1-4, näher erläutert werden;The invention is based on 30 substances as an embodiment examples according to general regulations a) to f), including the test results are explained in Tables 1-4;

a) Steroidazomethinea) Steroid azomethines Allgemeine Vorschrift für die Substanzen 1-3, 17, 25, 27, 28, 30General regulation for substances 1-3, 17, 25, 27, 28, 30

2.0 mmol des jeweiligen Steroidamins werden mit 2.2 mmol der entsprechenden Aldehydverbindung in 30 ml absoluten Methanol 2 Stunden bei Raumtemperatur gerührt. Die ausgefallenen Kristalle werden abgesaugt und mit wenig kalten Methanol und Ether gewaschen und anschließend getrocknet.2.0 mmol of the respective steroid amine are mixed with 2.2 mmol of the corresponding aldehyde compound in 30 ml of absolute methanol for 2 hours stirred at room temperature. The precipitated crystals are suctioned off and washed with a little cold methanol and ether and then dried.

b) (Arylalkyl)aminosteroideb) (arylalkyl) aminosteroids Allgemeine Vorschrift für die Substanzen 4-9General rule for substances 4-9

1.33 mmol des jeweiligen Steroidamins werden in 1 ml absoluten Methanol und 20 mmol der entsprechenden Arylvinylverbindung gelöst. Nach Zugabe von 80 mg Essigsäure wird unter Argon 48 Stunden bei etwa 75-80°C gerührt. Danach werden das Methanol und die überschüssige Vinylverbin­ dung unter Vakuum abdestilliert. Das Produkt wird in 10 ml Methanol gelöst. Zu der Lösung gibt man 1 ml methanolische NaOH-Lösung. Nach Einengen bis zur Trockene wird der Rückstand in 40 ml Ether aufgenommen, filtriert, eingeengt und über Kieselgel mit Methanol säulen-chromatographisch getrennt.1.33 mmol of the respective steroid amine are dissolved in 1 ml of absolute methanol and 20 mmol of the corresponding aryl vinyl compound dissolved. After encore 80 mg of acetic acid is made under argon for 48 hours at about 75-80 ° C touched. After that, the methanol and the excess vinyl compound dung distilled off under vacuum. The product is dissolved in 10 ml of methanol. 1 ml of methanolic NaOH solution is added to the solution. After constriction the residue is taken up to dryness in 40 ml of ether, filtered,  concentrated and column chromatographed over silica gel with methanol Cut.

c) Sekundäre Steroidaminec) Secondary steroid amines Allgemeine Vorschrift für die Substanzen 10-11, 18-22, 24, 26, 29General regulation for substances 10-11, 18-22, 24, 26, 29

1.0 mmol des jeweiligen Steroidcarbaldimins (Teilweise wurden auch die Reaktionsgemische aus der Umsetzung eines Steroidamins mit dem entsprechenden Aldehyd verwendet.) werden in 40 ml absoluten Methanol gelöst. Unter Argon werden 80 mg (2.1 mmol) NaBH4 bei Raumtemperatur zugegeben. Nach einer Stunde wird etwa 1 ml Wasser zugesetzt und weitere 10 min gerührt. Anschließend wird bis zur Trockene eingeengt und der Rückstand in 30 ml CH2Cl2 aufgenommen. Die Lösung wird mehrmals mit ca. 50 ml Wasser extrahiert. Nach Trocknung der Lösung über Na2SO4 wird bis zur Trockene eingeengt. Man erhält feinkristalline Produkte.1.0 mmol of the respective steroid carbaldimine (in some cases the reaction mixtures from the reaction of a steroid amine with the corresponding aldehyde were used) are dissolved in 40 ml of absolute methanol. 80 mg (2.1 mmol) of NaBH 4 are added at room temperature under argon. After one hour, about 1 ml of water is added and the mixture is stirred for a further 10 min. The mixture is then evaporated to dryness and the residue is taken up in 30 ml of CH 2 Cl 2 . The solution is extracted several times with about 50 ml of water. After the solution has been dried over Na 2 SO 4 , the mixture is evaporated to dryness. Finely crystalline products are obtained.

d) Steroidammoniumsalzed) Steroid ammonium salts Allgemeine Vorschrift für die Substanzen 12-14, 23General regulation for substances 12-14, 23

2.0 mmol des entsprechenden Steroidamins werden in 10 ml absoluten Methanol mit 2.2 mmol Ammoniumhalogenid, Alkylhalogenid oder einer Carbonsäure bei Raumtemperatur 2-4 Stunden umgesetzt. Die Reaktions­ mischung wird bis zur Trockene eingeengt, das Produkt in 50 ml Methylen­ chlorid gelöst und mehrmals mit Wasser gewaschen. Die Lösung wird über Natriumsulfat getrocknet. Nach Einengen und Abkühlen erhält man kristalline Produkte. 2.0 mmol of the corresponding steroid amine are absolute in 10 ml Methanol with 2.2 mmol ammonium halide, alkyl halide or one Carboxylic acid reacted at room temperature for 2-4 hours. The reaction mixture is evaporated to dryness, the product in 50 ml of methylene chloride dissolved and washed several times with water. The solution is over Dried sodium sulfate. After concentration and cooling you get crystalline products.  

e) Tertiäre Steroidaminee) Tertiary steroid amines Allgemeine Vorschrift für die Substanzen 15General regulation for substances 15

0.228 mmol des entsprechenden primären Steroidamins werden in 10 ml Methylenchlorid gelöst. Zu dieser Lösung werden 50 mmol des jeweiligen Alkyl- oder Aryljodids und Stunden gerührt. Die Reaktionsmischung wird filtriert und bis zur Trockene eingeengt. Man erhält die tertiären Amine als feste Substanzen.0.228 mmol of the corresponding primary steroidamine are in 10 ml Dissolved methylene chloride. 50 mmol of the respective are added to this solution Alkyl or aryl iodide and stirred for hours. The reaction mixture is filtered and evaporated to dryness. The tertiary amines are obtained as solid substances.

f) Acetamidosteroidef) acetamidosteroids Allgemeine Vorschrift für die Substanzen 16General regulation for substances 16

0.68 mmol des entsprechenden sekundären Steroidamins werden in 3 ml Pyridin und 1.5 ml Acetanhydrid gelöst und 24 Stunden bei Raumtemperatur gerührt. Anschließend wird das Reaktionsgemisch unter Rühren in 100 ml Eiswasser gegossen. Das feste Produkt wird abfiltriert, mit Wasser gewaschen und im Vakuum getrocknet. Säulenchromatographisch wird danach über Al2O3 mit Heptan/Essigsäureethylester im Verhältnis 5 : 1 von Nebenprodukten abgetrennt. Nach Entfernung der Lösungsmittel erhält man die entsprechenden Acetamidosteroide als kristalline Produkte.0.68 mmol of the corresponding secondary steroidamine are dissolved in 3 ml of pyridine and 1.5 ml of acetic anhydride and stirred for 24 hours at room temperature. The reaction mixture is then poured into 100 ml of ice water with stirring. The solid product is filtered off, washed with water and dried in vacuo. Column chromatography then separates from by-products over Al 2 O 3 with heptane / ethyl acetate in a ratio of 5: 1. After removal of the solvents, the corresponding acetamidosteroids are obtained as crystalline products.

  • 1. Substanz 1: 16α-(Ferrocencarbaldimino)-17β-hydroxy-3-methoxy-estra- 1,3,5(10)-trien Formel 1 mit a = 0, R = 17β-hydroxy-3-methoxy-estra- 1,3,5(10)-trien-16α-yl, R1, R2 = Bindung, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl, C30H35FeNO2 (497.55),
    erhalten durch Umsetzung von 16α-Amino-17β-hydroxy-3-methoxy-estra- 1,3,5(10)-trien und Ferrocencarbaldehyd.
    Ausbeute: 82.4% d. Th., orangefarbene Kristalle, Fp. 193-197°C (Zersetzg.).
    Berechnet:
    C 72.42, H 7.09, N 2.82;
    Gefunden:
    C 72.29, H 7.22, N 2.74%.
    1H-NMR(CDCl3) δ = 0.974 (s, 3H, 18-CH3); 3.767 (s, 3H, OCH3); 4.149 (s, 5H, C5H5); 4.295 (m, 2H, C5H4); 4.618 (m, 2H, C5H4); 6.63-6.73 (m, 2H, C6H3); 7.20-7.25 (m, 1H, C6H3); 8.108 (s, 1H, N=CH).
    13C-NMR (CDCl3) δ = 68.23 (s, C5H4); 68.62 (s, C5H4); 69.02 (s, C5H5); 70.21 (s, C5H4); 81.10 (s, C5H4); 158.83 (s, N=CH).    1. Substance 1: 16α- (ferrocenecarbaldimino) -17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene formula 1 with a = 0, R = 17β-hydroxy-3-methoxy-estra- 1,3,5 (10) -trien-16α-yl, R 1 , R 2 = bond, R 4 = H, R 3 with x = 0 and R 6 = ferrocenyl, C 30 H 35 FeNO 2 (497.55),
    obtained by reacting 16α-amino-17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and ferrocene carbaldehyde.
    Yield: 82.4% of theory. Th., Orange crystals, mp 193-197 ° C (decomp.).
    Calculated:
    C 72.42, H 7.09, N 2.82;
    Found:
    C 72.29, H 7.22, N 2.74%.
    1 H NMR (CDCl 3 ) δ = 0.974 (s, 3H, 18-CH 3 ); 3,767 (s, 3H, OCH 3 ); 4,149 (s, 5H, C 5 H 5 ); 4.295 (m, 2H, C 5 H 4); 4,618 (m, 2H, C 5 H 4 ); 6.63-6.73 (m, 2H, C 6 H 3); 7.20-7.25 (m, 1H, C 6 H 3 ); 8.108 (s, 1H, N = CH).
    13 C NMR (CDCl 3 ) δ = 68.23 (s, C 5 H 4 ); 68.62 (s, C 5 H 4); 69.02 (s, C 5 H 5 ); 70.21 (s, C 5 H 4); 81.10 (s, C 5 H 4); 158.83 (s, N = CH).
  • 2. Substanz 2: 16β-(Ferrocencarbaldimino)-17α-hydroxy-3-methoxy-estra- 1,3,5(10)-trien Formel 1 mit a = 0, R = 17α-hydroxy-3-methoxy-estra- 1,3,5(10)-trien-16β-yl, R1, R2 = Bindung, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl, C30H35FeNO2 (497.55),
    erhalten durch Umsetzung von 16β-Amino-17α-hydroxy-3-methoxy-estra- 1,3,5(10)-trien und Ferrocencarbaldehyd.
    Ausbeute: 83.1% d. Th., orangefarbene Kristalle, Fp. 182-184°C (Methanol). Berechnet:
    C 72.42, H 7.09, N 2.82;
    Gefunden:
    C 72.76, H 7.03, N 2.76%.
    1H-NMR(CDCl3): δ = 0.975 (s, 3H, 18-CH3); 3.767 (s, 3H, OCH3); 4.149 (s, 5H, C5H5); 4.324 (m, 2H, C5H4); 4.618 (m, 2H, C5H4); 6.63-6.73 (m, 2H, C6H3); 7.20-7.25 (m, 1H, C6H3); 8.111 (s, 1H, N=CH).
    13C-NMR (CDCl3): δ = 68.53 (s, C5H4); 68.71 (s, C5H4); 69.18 (s, C5H5); 70.34 (s, C5H4); 80.34 (s, C5H4); 160.33 (s, N=CH).    2. Substance 2: 16β- (ferrocenecarbaldimino) -17α-hydroxy-3-methoxy-estra- 1,3,5 (10) -triene formula 1 with a = 0, R = 17α-hydroxy-3-methoxy-estra- 1,3,5 (10) -trien-16β-yl, R 1 , R 2 = bond, R 4 = H, R 3 with x = 0 and R 6 = ferrocenyl, C 30 H 35 FeNO 2 (497.55),
    obtained by reacting 16β-amino-17α-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and ferrocene carbaldehyde.
    Yield: 83.1% of theory. Th., Orange crystals, mp. 182-184 ° C (methanol). Calculated:
    C 72.42, H 7.09, N 2.82;
    Found:
    C 72.76, H 7.03, N 2.76%.
    1 H NMR (CDCl 3 ): δ = 0.975 (s, 3H, 18-CH 3 ); 3,767 (s, 3H, OCH 3 ); 4,149 (s, 5H, C 5 H 5 ); 4,324 (m, 2H, C 5 H 4 ); 4,618 (m, 2H, C 5 H 4 ); 6.63-6.73 (m, 2H, C 6 H 3); 7.20-7.25 (m, 1H, C 6 H 3 ); 8.111 (s, 1H, N = CH).
    13 C NMR (CDCl 3 ): δ = 68.53 (s, C 5 H 4 ); 68.71 (s, C 5 H 4); 69.18 (s, C 5 H 5); 70.34 (s, C 5 H 4); 80.34 (s, C 5 H 4); 160.33 (s, N = CH).
  • 3. Substanz 3: 16β-(Ferrocencarbaldimino)-3-methoxy-estra-1,3,5(10)- trien Formel 1 mit a = 0, R = 3-methoxy-estra-1,3,5(10)-trien-16β-yl, R1, R2 = Bindung, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl, C3H35FeNO (481.46), erhalten durch Umsetzung von 16β-Amino-3-methoxy-estra-1,3,5(10)-trien und Ferrocencarbaldehyd.
    Ausbeute: 78.2% d. Th., orangefarbene Kristalle, Fp. 210-212°C (Methanol).
    Berechnet:
    C 74.84, H 7.33, N 2.91;
    Gefunden:
    C 74.05, H 7.39, N 2.82%.
    1H-NMR(CDCl3): δ = 1.031 (s, 3H, 18-CH3); 3.798 (s, m (überlagert), 4H, OCH3, 16-CH); 4.144 (s, 5H, C5H5); 4.302 (m, 2H, C5H4); 4.608 (m, 2H, C5H4); 8.018 (s, 1H, N=CH).
    13C-NMR(CDCl3): δ = 19.32 (s, 18-CH3); 55.21 (s, OCH3); 68.26 (s, C5H4); 68.40 (s, C5H4); 68.50 (s, 16-C); 68.97 (s, C5H5); 70.03 (s, C5H4); 81.46 (s, C5H4); 157.23 (s, N=CH); 157.38 (s, 3-C).    3.Substance 3: 16β- (ferrocenecarbaldimino) -3-methoxy-estra-1,3,5 (10) - triene formula 1 with a = 0, R = 3-methoxy-estra-1,3,5 (10) -trien-16β-yl, R 1 , R 2 = bond, R 4 = H, R 3 with x = 0 and R 6 = ferrocenyl, C 3 H 35 FeNO (481.46), obtained by reaction of 16β-amino-3 -methoxy-estra-1,3,5 (10) -triene and ferrocene carbaldehyde.
    Yield: 78.2% of theory. Th., Orange crystals, mp 210-212 ° C (methanol).
    Calculated:
    C 74.84, H 7.33, N 2.91;
    Found:
    C 74.05, H 7.39, N 2.82%.
    1 H NMR (CDCl 3 ): δ = 1,031 (s, 3H, 18-CH 3 ); 3,798 (s, m (overlaid), 4H, OCH 3 , 16-CH); 4,144 (s, 5H, C 5 H 5 ); 4,302 (m, 2H, C 5 H 4 ); 4,608 (m, 2H, C 5 H 4 ); 8,018 (s, 1H, N = CH).
    13 C NMR (CDCl 3 ): δ = 19.32 (s, 18-CH 3 ); 55.21 (s, OCH 3 ); 68.26 (s, C 5 H 4); 68.40 (s, C 5 H 4); 68.50 (s, 16-C); 68.97 (s, C 5 H 5); 70.03 (s, C 5 H 4 ); 81.46 (s, C 5 H 4); 157.23 (s, N = CH); 157.38 (s, 3-C).
  • 4. Substanz 4: N-(2-(α-Pyridyl)ethyl)-16β-amino-3-methoxyestra- 1,3,5(10)-trien-17β-ol Formel 1 mit a = 0, R = 17β-Hydroxy-3-methoxy­ estra-1,3,5(10)-trien-16β-yl, R1, R2, R4 = H, R3 mit x = 1 und R6 = α-Pyridyl, C26H34N2O2 (M = 406.57),
    erhalten durch Umsetzung von 16β-Amino-3-methoxyestra-1,3,5(10)-trien- 17β-ol und α-Vinylpyridin.
    Ausbeute: 75.8% d. Th., farbloser Feststoff, MS(EI): 406[M+].
    Berechnet:
    C 76.81, H 8.43, N 6.89;
    Gefunden:
    C 77.09, H 8.73, N 6.71%.
    1H-NMR(CDCl3): δ = 0.622 (s, 3H, 18-CH3); 2.807 (m, 2H, 6-CH2); 3.364 (d, 3J(1H, 1H) = 8.8 Hz, 2H, 17-CH); 3.746 (s, 3H, OCH3); 6.58-6.71 (m, 2H, C6H3); 7.08-7.20 (m, 3H, C6H3, C5H4N); 7.585 (m, 1H, C5H4N); 8.510 (m, 1H, C5H4N).
    13CNMR(CDCl3): δ = 12.30 (s, 18-CH3); 55.16 (s, OCH3); 58.05 (s, 16-C); 79.06 (s, 17-C); 111.42 (s, C6H3); 113.78 (s, C6H3); 121.30 (s, C5H4N); 123.28 (s, C5H4N); 126.30 (s, C6H3); 132.69 (s, C6H3); 136.37 (s, C5H4N); 137.76 (s, C6H3); 149.29 (s, C5H4N); 157.43 (s, C6H3); 160.00 (s, C5H4N).    4. Substance 4: N- (2- (α-pyridyl) ethyl) -16β-amino-3-methoxyestra-1,3,5 (10) -trien-17β-ol formula 1 with a = 0, R = 17β -Hydroxy-3-methoxy estra-1,3,5 (10) -triene-16β-yl, R 1 , R 2 , R 4 = H, R 3 with x = 1 and R 6 = α-pyridyl, C 26 H 34 N 2 O 2 (M = 406.57),
    obtained by reacting 16β-amino-3-methoxyestra-1,3,5 (10) -trien-17β-ol and α-vinylpyridine.
    Yield: 75.8% of theory. Th., Colorless solid, MS (EI): 406 [M + ].
    Calculated:
    C 76.81, H 8.43, N 6.89;
    Found:
    C 77.09, H 8.73, N 6.71%.
    1 H NMR (CDCl 3 ): δ = 0.622 (s, 3H, 18-CH 3 ); 2.807 (m, 2H, 6-CH 2); 3.364 (d, 3 J (1 H, 1 H) = 8.8 Hz, 2H, 17-CH); 3,746 (s, 3H, OCH 3 ); 6.58-6.71 (m, 2H, C 6 H 3 ); 7.08-7.20 (m, 3H, C 6 H 3 , C 5 H 4 N); 7,585 (m, 1H, C 5 H 4 N); 8,510 (m, 1H, C 5 H 4 N).
    13 CNMR (CDCl 3 ): δ = 12.30 (s, 18-CH 3 ); 55.16 (s, OCH 3 ); 58.05 (s, 16-C); 79.06 (s, 17-C); 111.42 (s, C 6 H 3); 113.78 (s, C 6 H 3 ); 121.30 (s, C 5 H 4 N); 123.28 (s, C 5 H 4 N); 126.30 (s, C 6 H 3 ); 132.69 (s, C 6 H 3 ); 136.37 (s, C 5 H 4 N); 137.76 (s, C 6 H 3); 149.29 (s, C 5 H 4 N); 157.43 (s, C 6 H 3 ); 160.00 (s, C 5 H 4 N).
  • 5. Substanz 5: N-(2-(α-Pyridyl)ethyl)-16α-amino-3-methoxyestra- 1,3,5(10)-trien-17β-ol Formel 1 mit a = 0, R = 17β-Hydroxy-3-methoxy­ estra-1,3,5(10)-trien-16α-yl, R1, R2, R4 = H, R3 mit x = 1 und R6 = α-Pyridyl, C26H34N2O2 (m = 406.57),
    erhalten durch Umsetzung von 16α-Amino-3-methoxyestra-1,3,5(10)-trien- 17β-ol und α-Vinylpyridin.
    Ausbeute: 37% d. Th., farbloser Feststoff, MS(EI): 406[M+].
    Berechnet:
    C 76.81, H 8.43, N 6.89;
    Gefunden:
    C 77.09, H 8.73, N 6.71%;
    [α]D 20 = 30.4°.
    1H-NMR(CDCl3): δ = 0.810 (s, 3H, 18-CH3); 2.806 (m, 2H, 6-CH2); 3.441 (m, 2H, 17-CH); 3.745 (s, 3H, OCH3); 6.59-6.70 (m, 2H, C6H3); 7.09-7.18 (m, 3H, C6H3, C5H4N); 7.603 (m, 1H, C5H4N); 8.503 (m, 1H, C5H4N).
    13C-NMR(CDCl3): δ = 12.26 (s, 18-CH3); 55.17 (s, OCH3); 63.90 (s, 16-C); 87.94 (s, 17-C); 111.43 (s, C6H3); 113.80 (s, C6H3); 121.33 (s, C5H4N); 123.40 (s, C5H4N); 126.20 (s, C6H3); 132.57 (s, C6H3); 136.56 (s, C5H4N); 137.90 (s, C6H3); 149.16 (s, C5H4N); 157.42 (s, C6H3); 160.16 (s, C5H4N).    5. Substance 5: N- (2- (α-pyridyl) ethyl) -16α-amino-3-methoxyestra-1,3,5 (10) -trien-17β-ol formula 1 with a = 0, R = 17β -Hydroxy-3-methoxy estra-1,3,5 (10) -triene-16α-yl, R 1 , R 2 , R 4 = H, R 3 with x = 1 and R 6 = α-pyridyl, C 26 H 34 N 2 O 2 (m = 406.57),
    obtained by reacting 16α-amino-3-methoxyestra-1,3,5 (10) -trien-17β-ol and α-vinylpyridine.
    Yield: 37% of theory Th., Colorless solid, MS (EI): 406 [M + ].
    Calculated:
    C 76.81, H 8.43, N 6.89;
    Found:
    C 77.09, H 8.73, N 6.71%;
    [α] D 20 = 30.4 °.
    1 H NMR (CDCl 3 ): δ = 0.810 (s, 3H, 18-CH 3 ); 2.806 (m, 2H, 6-CH 2); 3,441 (m, 2H, 17-CH); 3,745 (s, 3H, OCH 3 ); 6.59-6.70 (m, 2H, C 6 H 3 ); 7.09-7.18 (m, 3H, C 6 H 3 , C 5 H 4 N); 7,603 (m, 1H, C 5 H 4 N); 8.503 (m, 1H, C 5 H 4 N).
    13 C NMR (CDCl 3 ): δ = 12.26 (s, 18-CH 3 ); 55.17 (s, OCH 3 ); 63.90 (s, 16-C); 87.94 (s, 17-C); 111.43 (s, C 6 H 3 ); 113.80 (s, C 6 H 3 ); 121.33 (s, C 5 H 4 N); 123.40 (s, C 5 H 4 N); 126.20 (s, C 6 H 3 ); 132.57 (s, C 6 H 3 ); 136.56 (s, C 5 H 4 N); 137.90 (s, C 6 H 3); 149.16 (s, C 5 H 4 N); 157.42 (s, C 6 H 3 ); 160.16 (s, C 5 H 4 N).
  • 6. Substanz 6: N,N-Bis(2-(α-Pyridyl)ethyl)-16α-amino-3-methoxyestra- 1,3,5(10)-trien-17β-ol Formel 1 mit a = 0, R = 17β-Hydroxy-3-methoxy­ estra-1,3,5(10)-trien-16α-yl, R1 = 2-Pyridylethyl, R2, R4 = H, R3 mit x = 1 und R6 = α-Pyridyl, C33H41N3O2 (M = 511.72),
    erhalten durch Umsetzung von 16α-Amino-3-methoxyestra-1,3,5(10)-trien- 17β-ol und α-Vinylpyridin.
    Ausbeute: 34.0% d. Th., farbloses zähes Öl, MS(EI): 512[M+].
    Berechnet:
    C 77.46, H 8.07, N 8.21;
    Gefunden:
    C 77.19, H 8.23, N 8.01%.
    1H-NMR(CDCl3): δ = 0.817 (s, 3H, 18-CH3); 3.743 (s, 3H, OCH3); 6.59-6.70 (m, 2H, C6H3); 6.93-7.19 (m, 5H, C6H3, C5H4N); 7.530 (m, 2H, C5H4N); 8.490 (m, 2H, C5H4N).
    13C-NMR(CDCl3): δ = 12.28 (s, 18-CH3); 55.16 (s, OCH3); 66.20 (s, 16-C); 83.81 (s, 17-C); 111.38 (s, C6H3); 113.79 (s, C6H3); 121.08 (s, C5H4N); 123.48 (s, C5H4N); 126.21 (s, C6H3); 132.79 (s, C6H3); 136.27 (s, C5H4N); 137.91 (s, C6H3); 149.00 (s, C5H4N); 157.39 (s, C6H3); 160.68 (s, C5H4N).    6.Substance 6: N, N-bis (2- (α-pyridyl) ethyl) -16α-amino-3-methoxyestra-1,3,5 (10) -trien-17β-ol formula 1 with a = 0, R = 17β-hydroxy-3-methoxy estra-1,3,5 (10) -trien-16α-yl, R 1 = 2-pyridylethyl, R 2 , R 4 = H, R 3 with x = 1 and R 6 = α-pyridyl, C 33 H 41 N 3 O 2 (M = 511.72),
    obtained by reacting 16α-amino-3-methoxyestra-1,3,5 (10) -trien-17β-ol and α-vinylpyridine.
    Yield: 34.0% of theory. Th., Colorless viscous oil, MS (EI): 512 [M + ].
    Calculated:
    C 77.46, H 8.07, N 8.21;
    Found:
    C 77.19, H 8.23, N 8.01%.
    1 H NMR (CDCl 3 ): δ = 0.817 (s, 3H, 18-CH 3 ); 3,743 (s, 3H, OCH 3 ); 6.59-6.70 (m, 2H, C 6 H 3 ); 6.93-7.19 (m, 5H, C 6 H 3 , C 5 H 4 N); 7.530 (m, 2H, C 5 H 4 N); 8,490 (m, 2H, C 5 H 4 N).
    13 C NMR (CDCl 3 ): δ = 12.28 (s, 18-CH 3 ); 55.16 (s, OCH 3 ); 66.20 (s, 16-C); 83.81 (s, 17-C); 111.38 (s, C 6 H 3); 113.79 (s, C 6 H 3 ); 121.08 (s, C 5 H 4 N); 123.48 (s, C 5 H 4 N); 126.21 (s, C 6 H 3 ); 132.79 (s, C 6 H 3 ); 136.27 (s, C5H 4 N); 137.91 (s, C 6 H 3 ); 149.00 (s, C 5 H 4 N); 157.39 (s, C 6 H 3); 160.68 (s, C 5 H 4 N).
  • 7. Substanz 7: N-(2-(α-Pyridyl)ethyl)-16α-amino-3-methoxyestra- 1,3,5(10)-trien-17α-ol Formel 1 mit a = 0, R = 17α-Hydroxy-3-methoxy­ estra-1,3,5(10)-trien-16α-yl, R1, R2, R4 = H, R3 mit x = 1 und R6 = α- Pyridyl, C26H34N2O2 (M = 406.57),
    erhalten durch Umsetzung von 16α-Amino-3-methoxyestra-1,3,5(10)-trien- 17β-ol und α-Vinylpyridin.
    Ausbeute: 56.3% d. Th., gelbliches Öl, MS(EI): 406[M+].
    Berechnet:
    C 76.81, H 8.43, N 6.89;
    Gefunden:
    C 76.19, H 8.40, N 6.88%;
    [α]D 20 = 24.9°.
    1H-NMR(CDCl3): δ = 0.710 (s, 3H, 18-CH3); 2.809 (m, 2H, 6-CH2); 3.556 (d, 3J(1H, 1H) = 4.75 Hz, 2H, 17-CH); 3.746 (s, 3H, OCH3); 6.58-6.71 (m, 2H, C6H3); 7.09-7.21 (m, 3H, C6H3, C5H4N); 7.614 (m, 1H, C5H4N); 8.524 (m, 1H, C5H4N).
    13C-NMR(CDCl3): δ = 16.85 (s, 18-CH3); 55.18 (s, OCH3); 59.78 (s, 16-C); 76.36 (s, 17-C); 111.40 (s, C6H3); 113.80 (s, C6H3); 121.41 (s, C5H4N); 123.35 (s, C5H4N); 126.31 (s, C6H3); 132.93 (s, C6H3); 136.51 (s, C5H4N); 137.89 (s, C6H3); 149.27 (s, C5H4N); 157.38 (s, C6H3); 159.85 (s, C5H4N).    7. Substance 7: N- (2- (α-pyridyl) ethyl) -16α-amino-3-methoxyestra-1,3,5 (10) -trien-17α-ol formula 1 with a = 0, R = 17α -Hydroxy-3-methoxy estra-1,3,5 (10) -triene-16α-yl, R 1 , R 2 , R 4 = H, R 3 with x = 1 and R 6 = α-pyridyl, C 26 H 34 N 2 O 2 (M = 406.57),
    obtained by reacting 16α-amino-3-methoxyestra-1,3,5 (10) -trien-17β-ol and α-vinylpyridine.
    Yield: 56.3% of theory. Th., Yellowish oil, MS (EI): 406 [M + ].
    Calculated:
    C 76.81, H 8.43, N 6.89;
    Found:
    C 76.19, H 8.40, N 6.88%;
    [α] D 20 = 24.9 °.
    1 H NMR (CDCl 3 ): δ = 0.710 (s, 3H, 18-CH 3 ); 2.809 (m, 2H, 6-CH 2); 3.556 (d, 3 J (1 H, 1 H) = 4.75 Hz, 2H, 17-CH); 3,746 (s, 3H, OCH 3 ); 6.58-6.71 (m, 2H, C 6 H 3 ); 7.09-7.21 (m, 3H, C 6 H 3 , C 5 H 4 N); 7,614 (m, 1H, C 5 H 4 N); 8,524 (m, 1H, C 5 H 4 N).
    13 C NMR (CDCl 3 ): δ = 16.85 (s, 18-CH 3 ); 55.18 (s, OCH 3 ); 59.78 (s, 16-C); 76.36 (s, 17-C); 111.40 (s, C 6 H 3); 113.80 (s, C 6 H 3 ); 121.41 (s, C 5 H 4 N); 123.35 (s, C 5 H 4 N); 126.31 (s, C 6 H 3 ); 132.93 (s, C 6 H 3); 136.51 (s, C 5 H 4 N); 137.89 (s, C 6 H 3); 149.27 (s, C 5 H 4 N); 157.38 (s, C 6 H 3); 159.85 (s, C 5 H 4 N).
  • 8. Substanz 8: N,N-Bis(2-(α-Pyridyl)ethyl)-16α-amino-3-methoxyestra- 1,3,5(10)-trien-17α-ol Formel 1 mit a = 0, R = 17α-Hydroxy-3-methoxy­ estra-1,3,5(10)-trien-16α-yl, R1 = 2-Pyridylethyl, R2, R4 = H, R3 mit x = 1 und R6 = α-Pyridyl, C33H41N3O2 (m = 511.72),
    erhalten durch Umsetzung von 16α-Amino-3-methoxyestra-1,3,5(10)-trien- 17β-ol und α-Vinylpyridin.
    Ausbeute: 21.1% d. Th., gelbliches Öl, MS(EI): 512[M+].
    Berechnet:
    C 77.46, H 8.07, N 8.21;
    Gefunden:
    C 76.68, H 8.24, N 8.26%;
    [α]D 20 = 39.9°.
    1H-NMR(CDCl3): 6 = 0.717 (s, 3H, 18-CH3); 3.616 (m, 1H, 17-CH); 3.750 (s, 3H, OCH3); 6.59-6.71 (m, 2H, C6H3); 7.06-7.21 (m, 5H, C6H3, C5H4N); 7.560 (m, 2H, C5H4N); 8.515 (m, 2H, C5H4N).
    13C-NMR(CDCl3): δ = 17.15 (s, 18-CH3); 55.19 (s, OCH3); 64.52 (s, 16-C); 78.32 (s, 17-C); 111.39 (s, C6H3); 113.80 (s, C6H3); 121.21 (s, C5H4N); 123.34 (s, C5H4N); 126.26 (s, C6H3); 132.98 (s, C6H3); 136.32 (s, C5H4N); 137.90 (s, C6H3); 149.32 (s, C5H4N); 157.39 (s, C6H3); 160.09 (s, C5H4N).    8. Substance 8: N, N-bis (2- (α-pyridyl) ethyl) -16α-amino-3-methoxyestra-1,3,5 (10) -triene-17α-ol formula 1 with a = 0, R = 17α-hydroxy-3-methoxy estra-1,3,5 (10) -trien-16α-yl, R 1 = 2-pyridylethyl, R 2 , R 4 = H, R 3 with x = 1 and R 6 = α-pyridyl, C 33 H 41 N 3 O 2 (m = 511.72),
    obtained by reacting 16α-amino-3-methoxyestra-1,3,5 (10) -trien-17β-ol and α-vinylpyridine.
    Yield: 21.1% of theory. Th., Yellowish oil, MS (EI): 512 [M + ].
    Calculated:
    C 77.46, H 8.07, N 8.21;
    Found:
    C 76.68, H 8.24, N 8.26%;
    [α] D 20 = 39.9 °.
    1 H NMR (CDCl 3 ): 6 = 0.717 (s, 3H, 18-CH 3 ); 3,616 (m, 1H, 17-CH); 3,750 (s, 3H, OCH 3 ); 6.59-6.71 (m, 2H, C 6 H 3 ); 7.06-7.21 (m, 5H, C 6 H 3 , C 5 H 4 N); 7,560 (m, 2H, C 5 H 4 N); 8,515 (m, 2H, C 5 H 4 N).
    13 C NMR (CDCl 3 ): δ = 17.15 (s, 18-CH 3 ); 55.19 (s, OCH 3 ); 64.52 (s, 16-C); 78.32 (s, 17-C); 111.39 (s, C 6 H 3 ); 113.80 (s, C 6 H 3 ); 121.21 (s, C 5 H 4 N); 123.34 (s, C 5 H 4 N); 126.26 (s, C 6 H 3 ); 132.98 (s, C 6 H 3); 136.32 (s, C 5 H 4 N); 137.90 (s, C 6 H 3); 149.32 (s, C 5 H 4 N); 157.39 (s, C 6 H 3); 160.09 (s, C 5 H 4 N).
  • 9. Substanz 9: N-(2-(α-Pyridyl)ethyl)-16β-amino-3-methoxyestra- 1,3,5(10)-trien-17α-ol Formel 1 mit a = 0, R = 17α-Hydroxy-3-methoxy­ estra-1,3,5(10)-trien-16β-yl, R1, R2, R4 = H, R3 mit x = 1 und R6 = α- Pyridyl, C26H34N2O2 (M = 406.57),
    erhalten durch Umsetzung von 16β-Amino-3-methoxyestra-1,3,5(10)-trien- 17α-ol und α-Vinylpyridin.
    Ausbeute: 46.2% d. Th., farbloses Öl, MS(EI): 406[M+].
    Berechnet:
    C 76.81, H 8.43, N 6.89;
    Gefunden:
    C 76.74, H 8.62, N 6.73%.
    1H-NMR(CDCl3): δ = 0.814 (s, 3H, 18-CH3); 2.863 (m, 2H, 6-CH2); 3.615 (m, 1H, 17-CH); 3.754 (s, 3H, OCH3); 6.61-6.71 (m, 2H, C6H3); 7.04-7.21 (m, 3H, C6H3, C5H4N); 7.572 (m, 1H, C5H4N); 8.489 (m, 1H, C5H4N).
    13C-NMR(CDCl3): δ = 17.82 (s, 18-CH3); 55.19 (s, OCH3); 68.50 (s, 16-C); 84.63 (s, 17-C); 111.46 (s, C6H3); 113.79 (s, C6H3); 121.34 (s, C5H4N); 123.34 (s, C5H4N); 126.25 (s, C6H3); 132.75 (s, C6H3); 136.47 (s, C5H4N); 137.92 (s, C6H3); 149.12 (s, C5H4N); 157.45 (s, C6H3); 160.23 (s, C5H4N).     9. Substance 9: N- (2- (α-pyridyl) ethyl) -16β-amino-3-methoxyestra-1,3,5 (10) -trien-17α-ol formula 1 with a = 0, R = 17α -Hydroxy-3-methoxy estra-1,3,5 (10) -triene-16β-yl, R 1 , R 2 , R 4 = H, R 3 with x = 1 and R 6 = α-pyridyl, C 26 H 34 N 2 O 2 (M = 406.57),
    obtained by reacting 16β-amino-3-methoxyestra-1,3,5 (10) -trien-17α-ol and α-vinylpyridine.
    Yield: 46.2% of theory. Th., Colorless oil, MS (EI): 406 [M + ].
    Calculated:
    C 76.81, H 8.43, N 6.89;
    Found:
    C 76.74, H 8.62, N 6.73%.
    1 H NMR (CDCl 3 ): δ = 0.814 (s, 3H, 18-CH 3 ); 2.863 (m, 2H, 6-CH 2); 3,615 (m, 1H, 17-CH); 3,754 (s, 3H, OCH 3 ); 6.61-6.71 (m, 2H, C 6 H 3 ); 7.04-7.21 (m, 3H, C 6 H 3 , C 5 H 4 N); 7,572 (m, 1H, C 5 H 4 N); 8,489 (m, 1H, C 5 H 4 N).
    13 C NMR (CDCl 3 ): δ = 17.82 (s, 18-CH 3 ); 55.19 (s, OCH 3 ); 68.50 (s, 16-C); 84.63 (s, 17-C); 111.46 (s, C 6 H 3); 113.79 (s, C 6 H 3 ); 121.34 (s, C 5 H 4 N); 123.34 (s, C 5 H 4 N); 126.25 (s, C 6 H 3 ); 132.75 (s, C 6 H 3); 136.47 (s, C 5 H 4 N); 137.92 (s, C 6 H 3 ); 149.12 (s, C 5 H 4 N); 157.45 (s, C 6 H 3); 160.23 (s, C 5 H 4 N).
  • 10. Substanz 10: 16α-(Ferrocenylmethyl)amino-17β-hydroxy-3-methoxy­ estra-1,3,5(10)-trien Formel 1 mit a = 0, R = 17β-Hydroxy-3-methoxy-estra- 1,3,5(10)-trien-16α-yl, R1, R2, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl,
    C30U37FeNO2 .H2O (517.50),
    erhalten durch Umsetzung von 16α-(Ferrocencarbaldimino)-17β-hydroxy-3- methoxy-estra-1,3,5(10)-trien und NaBH4.
    Ausbeute: 99% d. Th., gelber Feststoff, Fp. 146-148°C.
    Berechnet:
    C 69.62, H 7.59, N 2.71;
    Gefunden:
    C 69.58, H 7.45, N 2.83%.
    1H-NMR(CDCl3): δ = 0.870 (s, 3H, 18-CH3); 2.989 (m, 1H, 16-CH); 3.551 (s, 2H, Cp-CH2); 3.571 (s, 1H, 17-CH); 3.758 (s, 3H, OCH3); 4.090 (m, 2 H, C5H4); 4.108 (s, 5H, C5H5); 4.210 (m, 1H, C5H4); 4.325 (m, 1H, C5H4).
    13C-NHR(CDCl3): δ = 17.80 (s, 18-CH3); 47.86 (s, Cp-CH2); 55.20 (s, OCH3); 67.73 (s, C5H4); 67.82 (s, C5H4); 68.06 (s, 16-CH); 68.32 (s, C5H4); 68.40 (s, C5H5); 68.55 (s, C5H4); 86.91 (s, C5H4).    10. Substance 10: 16α- (ferrocenylmethyl) amino-17β-hydroxy-3-methoxy estra-1,3,5 (10) -triene formula 1 with a = 0, R = 17β-hydroxy-3-methoxy-estra- 1,3,5 (10) -triene-16α-yl, R 1 , R 2 , R 4 = H, R 3 with x = 0 and R 6 = ferrocenyl,
    C 30 U 37 FeNO 2 .H 2 O (517.50),
    obtained by reacting 16α- (ferrocenecarbaldimino) -17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and NaBH 4 .
    Yield: 99% of theory Th., Yellow solid, mp 146-148 ° C.
    Calculated:
    C 69.62, H 7.59, N 2.71;
    Found:
    C 69.58, H 7.45, N 2.83%.
    1 H NMR (CDCl 3 ): δ = 0.870 (s, 3H, 18-CH 3 ); 2,989 (m, 1H, 16-CH); 3.551 (s, 2H, Cp-CH2); 3,571 (s, 1H, 17-CH); 3,758 (s, 3H, OCH 3 ); 4.090 (m, 2 H, C 5 H 4); 4,108 (s, 5H, C 5 H 5 ); 4,210 (m, 1H, C 5 H 4 ); 4,325 (m, 1H, C 5 H 4 ).
    13 C-NHR (CDCl 3 ): δ = 17.80 (s, 18-CH 3 ); 47.86 (s, Cp-CH 2); 55.20 (s, OCH 3 ); 67.73 (s, C 5 H 4); 67.82 (s, C 5 H 4); 68.06 (s, 16-CH); 68.32 (s, C 5 H 4); 68.40 (s, C 5 H 5); 68.55 (s, C 5 H 4); 86.91 (s, C 5 H 4 ).
  • 11. Substanz 11: 16β-(Ferrocenylmethyl)amino-3-methoxy-estra-1,3,5(10)- trien Formel 1 mit a = 0, R = 3-Methoxy-estra-1,3,5(10)-trien-16β-yl, R1, R2, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl, C30H37FeNO.0.5H2O (492.46),
    erhalten durch Umsetzung von 16β-(Ferrocencarbaldimino)-3-methoxy-estra- 1,3,5(10)-trien und NaBH4.
    Ausbeute: 69.6% d. Th., gelber Feststoff, Fp = 133-135°C.
    Berechnet:
    C 73.17, H 7.77, N 2.84;
    Gefunden:
    C 73.06, H 7.88, N 2.70%.
    1H-NMR(CDCl3): δ = 0.918 (s, 3H, 18-CH3); 3.262 (m, 1H, 16-CH); 3.472 (m, 2H, Cp-CH2); 3.758 (s, 3H, OCH3); 4.082 (m, 2H, C5H4); 4.172 (s, 5H, C5H5); 4.181 (m, 2H, C5H4).
    13C-NMR(CDCl3): δ = 19.99 (s, 18-CH3); 47.57 (s, Cp-CH2); 55.20 (s, OCH3); 56.40 (s, 16-CH); 67.65 (s, C5H4); 67.68 (s, C5H4); 68.38 (s, C5H5); 87.09 (s, C5H4).    11.Substance 11: 16β- (ferrocenylmethyl) amino-3-methoxy-estra-1,3,5 (10) - triene formula 1 with a = 0, R = 3-methoxy-estra-1,3,5 (10 ) -triene-16β-yl, R 1 , R 2 , R 4 = H, R 3 with x = 0 and R 6 = ferrocenyl, C 30 H 37 FeNO.0.5H 2 O (492.46),
    obtained by reacting 16β- (ferrocenecarbaldimino) -3-methoxy-estra-1,3,5 (10) -triene and NaBH 4 .
    Yield: 69.6% of theory. Th., Yellow solid, mp = 133-135 ° C.
    Calculated:
    C 73.17, H 7.77, N 2.84;
    Found:
    C 73.06, H 7.88, N 2.70%.
    1 H NMR (CDCl 3 ): δ = 0.918 (s, 3H, 18-CH 3 ); 3,262 (m, 1H, 16-CH); 3.472 (m, 2H, Cp-CH2); 3,758 (s, 3H, OCH 3 ); 4,082 (m, 2H, C 5 H 4 ); 4,172 (s, 5H, C 5 H 5 ); 4,181 (m, 2H, C 5 H 4 ).
    13 C NMR (CDCl 3 ): δ = 19.99 (s, 18-CH 3 ); 47.57 (s, Cp CH 2 ); 55.20 (s, OCH 3 ); 56.40 (s, 16-CH); 67.65 (s, C 5 H 4); 67.68 (s, C 5 H 4); 68.38 (s, C 5 H 5); 87.09 (s, C 5 H 4 ).
  • 12. Substanz 12: 16α-(Ferrocenylmethyl)amino-17α-hydroxy-3-methoxy­ estra-1,3,5(10)-trien . HCl Formel 1 mit a = 1, R = 17α-Hydroxy-3-Methoxy­ estra-1,3,5(10)-trien-16α-yl, R1, R2, R4, R5 = H, R3 mit x = 0 und R6 = Ferrocenyl, A = Cl, C30H38ClFeNO2 (536.03),
    erhalten durch Umsetzung von 16α-(Ferrocenylmethyl)amino-17α-hydroxy- 3-methoxy-estra-1,3,5(10)-trien und NH4Cl.
    Ausbeute: 62.9% d. Th., gelbe Kristalle, Fp. 203-205°C. MS(EI): 499 [M-HCl]+ (isotopic pattern of Fe).
    Berechnet:
    C 67.22, H 6.96, N 2.61;
    Gefunden:
    C 66.88, H 7.18, N 2.61%.
    1H-NMR(CD3OD): δ = 0.757 (s, 3H, 18-CH3); 3.720 (s, 3H, OCH3); 4.223 (s, 5H, C5H5); 4.290 (m, 2H, C5H4); 4.409 (m, 2H, C5H4).
    13C-NMR(CD3OD): δ = 70.02 (s, C5H5); 70.61 (s, C5H4); 70.68 (s, C5H4); 71.27 (s, C5H4); 71.34 (s, C5H4).    12. Substance 12: 16α- (ferrocenylmethyl) amino-17α-hydroxy-3-methoxy estra-1,3,5 (10) -triene. HCl Formula 1 with a = 1, R = 17α-hydroxy-3-methoxy estra-1,3,5 (10) -trien-16α-yl, R 1 , R 2 , R 4 , R 5 = H, R 3 with x = 0 and R 6 = ferrocenyl, A = Cl, C 30 H 38 ClFeNO 2 (536.03),
    obtained by reacting 16α- (ferrocenylmethyl) amino-17α-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and NH 4 Cl.
    Yield: 62.9% of theory. Th., Yellow crystals, mp. 203-205 ° C. MS (EI): 499 [M-HCl] + (isotopic pattern of Fe).
    Calculated:
    C 67.22, H 6.96, N 2.61;
    Found:
    C 66.88, H 7.18, N 2.61%.
    1 H NMR (CD 3 OD): δ = 0.757 (s, 3H, 18-CH 3 ); 3,720 (s, 3H, OCH 3 ); 4.223 (s, 5H, C 5 H 5); 4.290 (m, 2H, C 5 H 4); 4,409 (m, 2H, C 5 H 4 ).
    13 C NMR (CD 3 OD): δ = 70.02 (s, C 5 H 5 ); 70.61 (s, C 5 H 4); 70.68 (s, C 5 H 4); 71.27 (s, C 5 H 4); 71.34 (s, C 5 H 4 ).
  • 13. Substanz 13: 16β-(Ferrocenylmethyl)amino-17α-hydroxy-3-methoxy­ estra-1,3,5(10)-trien . HCl Formel 1 mit a = 1, R = 17α-Hydroxy-3-Methoxy­ estra-1,3,5(10)-trien-16β-yl, R1, R2, R4, R5 = H, R3 mit x = 0 und R6 = Ferrocenyl, A = Cl, C30H38ClFeNO2 (536.03),
    erhalten durch Umsetzung von 16β-(Ferrocenylmethyl)amino-17α-hydroxy- 3-methoxy-estra-1,3,5(10)-trien und NH4Cl.
    Ausbeute: 49.5% d. Th., gelbe Kristalle, Fp. 203-206°C (Zersetzg.). MS (EI): 499[M-HCl]+ (isotopic pattern of Fe).
    Berechnet:
    C 67.22, H 6.96, N 2.61;
    Gefunden:
    C 66.82, H 6.90, N 2.62%.
    1H-NMR(CDCl3): δ = 0.993 (s, 3H, 18-CH3); 3.752 (s, 3H, OCH3); 3.990 (s, 2H, CH2-Cp); 4.163 (s, 5H, C5H5); 4.245 (m, 2H, C5H4); 4.433 (m, 1H, C5H4); 4.541 (m, 1H, C5H4).
    13C-NMR(CDCl3): δ = 68.91 (s, C5H5); 69.43 (s, C5H4); 69.71 (s, C5H4); 70.66 (s, C5H4); 71.23 (s, C5H4).    13. Substance 13: 16β- (ferrocenylmethyl) amino-17α-hydroxy-3-methoxy estra-1,3,5 (10) -triene. HCl Formula 1 with a = 1, R = 17α-hydroxy-3-methoxy estra-1,3,5 (10) -trien-16β-yl, R 1 , R 2 , R 4 , R 5 = H, R 3 with x = 0 and R 6 = ferrocenyl, A = Cl, C 30 H 38 ClFeNO 2 (536.03),
    obtained by reacting 16β- (ferrocenylmethyl) amino-17α-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and NH 4 Cl.
    Yield: 49.5% of theory. Th., Yellow crystals, mp. 203-206 ° C (decomp.). MS (EI): 499 [M-HCl] + (isotopic pattern of Fe).
    Calculated:
    C 67.22, H 6.96, N 2.61;
    Found:
    C 66.82, H 6.90, N 2.62%.
    1 H NMR (CDCl 3 ): δ = 0.993 (s, 3H, 18-CH 3 ); 3,752 (s, 3H, OCH 3 ); 3.990 (s, 2H, CH 2 -Cp); 4,163 (s, 5H, C 5 H 5 ); 4.245 (m, 2H, C 5 H 4); 4,433 (m, 1H, C 5 H 4 ); 4,541 (m, 1H, C 5 H 4 ).
    13 C NMR (CDCl 3 ): δ = 68.91 (s, C 5 H 5 ); 69.43 (s, C 5 H 4 ); 69.71 (s, C 5 H 4); 70.66 (s, C 5 H 4); 71.23 (s, C 5 H 4 ).
  • 14. Substanz 14: C26H34N2O2 .CH3COOH Formel 1 mit a = 1, R = 17β- Hydroxy-3-Methoxy-estra-1,3,5(10)-trien-16β-yl, R1, R2, R4, R5 = H, R3 mit x = 1 und R6 = α-Pyridyl, A = CH3COO, C28H38N2O4 (466.62),
    erhalten durch Umsetzung von N-(2-(α-Pyridyl)ethyl)-16β-amino-3- methoxyestra-1,3,5(10)-trien-17β-ol und CH3COOH.
    Ausbeute: ca. 100% d. Th., farblose Kristalle, Fp. 203-206°C (Zersetzg.). MS (EI): 406 [M-CH3COOH]+.
    Berechnet:
    C 72.07, H 8.21, N 6.00;
    Gefunden:
    C 72.02, H 8.09, N 6.26%.
    1H-NMR(CDCl3): δ = 0.896 (s, 3H, 18-CH3); 1.965 (s, 3H, CH 3COO); 2.807 (m, 2H, 6-CH2); 3.744 (s, 3H, OCH3); 3.839 (d, 3J(1H, 1H) = 8.72 Hz, 2H, 17-CH); 6.58-6.72 (m, 2H, C6H3); 7.13-7.20 (m, 3H, C6H3, C5H4N); 7.626 (m, 1H, C5H4N); 8.392 (m, 1H, C5H4N).
    13C-NMR(CDCl3): δ = 12.06 (s, 18-CH3); 55.16 (s, OCH3); 57.46 (s, 16-C); 78.17 (s, 17-C); 111.46 (s, C6H3); 113.81 (s, C6H3); 122.06 (s, C5H4N); 123.47 (s, C5H4N); 126.33 (s, C6H3); 132.36 (s, C6H3); 137.11 (s, C5H4N); 137.55 (s, C6H3); 148.66 (s, C5H4N); 157.49 (s, C6H3); 158.88 (s, C5H4N); 178.33 (s, COO).    14. Substance 14: C 26 H 34 N 2 O 2 .CH 3 COOH Formula 1 with a = 1, R = 17β-hydroxy-3-methoxy-estra-1,3,5 (10) -trien-16β-yl , R 1 , R 2 , R 4 , R 5 = H, R 3 with x = 1 and R 6 = α-pyridyl, A = CH 3 COO, C 28 H 38 N 2 O 4 (466.62),
    obtained by reacting N- (2- (α-pyridyl) ethyl) -16β-amino-3-methoxyestra-1,3,5 (10) -trien-17β-ol and CH 3 COOH.
    Yield: approx. 100% of theory Th., Colorless crystals, mp. 203-206 ° C (decomp.). MS (EI): 406 [M-CH 3 COOH] + .
    Calculated:
    C 72.07, H 8.21, N 6.00;
    Found:
    C 72.02, H 8.09, N 6.26%.
    1 H NMR (CDCl 3 ): δ = 0.896 (s, 3H, 18-CH 3 ); 1.965 (s, 3H, C H 3 COO); 2.807 (m, 2H, 6-CH 2); 3,744 (s, 3H, OCH 3 ); 3.839 (d, 3 J (1 H, 1 H) = 8.72 Hz, 2H, 17-CH); 6.58-6.72 (m, 2H, C 6 H 3); 7.13-7.20 (m, 3H, C 6 H 3 , C 5 H 4 N); 7,626 (m, 1H, C 5 H 4 N); 8,392 (m, 1H, C 5 H 4 N).
    13 C NMR (CDCl 3 ): δ = 12.06 (s, 18-CH 3 ); 55.16 (s, OCH 3 ); 57.46 (s, 16-C); 78.17 (s, 17-C); 111.46 (s, C 6 H 3); 113.81 (s, C 6 H 3 ); 122.06 (s, C 5 H 4 N); 123.47 (s, C 5 H 4 N); 126.33 (s, C 6 H 3 ); 132.36 (s, C 6 H 3); 137.11 (s, C 5 H 4 N); 137.55 (s, C 6 H 3); 148.66 (s, C 5 H 4 N); 157.49 (s, C 6 H 3 ); 158.88 (s, C 5 H 4 N); 178.33 (s, COO).
  • 15. Substanz 15: 16β-(Ferrocenylmethyl)ethylamino-17α-hydroxy-3- methoxy-estra-1,3,5(10)-trien Formel 1 mit a = 0, R = 17α-Hydroxy-3-
    Methoxy-estra-1,3,5(10)-trien-16β-yl, R1 = C2H5, R2, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl, C31H41FeNO2 (515.52),
    erhalten durch Umsetzung von 16β-(Ferrocenylmethyl)amino-17α-hydroxy- 3-methoxy-estra-1,3,5(10)-trien und C2H5I.
    Ausbeute: 80.6% d. Th., MS(EI): 527[M]+ (isotopic pattern of Fe).
    Berechnet:
    C 72.23, H 8.02, N 2.72;
    Gefunden:
    C 71.34, H 7.90, N 2.93%.
    1H-NMR(CDCl3): δ = 0.852 (s, 3H, 18-CH3); 1.001 (t, 3J(H-H) = 7.1 Hz, 3H, CH2CH 3); 2.549 (q, 3J(H-H) = 7.1 Hz, 2H, CH 2CH3); 3.758 (s, 3H, OCH3); 4.086 (s, 5H, C5H5); 4.173 (m, 2H, C5H4); 4.262 (m, 2H, C5H4). 13C-NMR(CDCl3): δ = 11.04 (s, CH2 CH3); 43.38 (s, CH2CH3); 68.30 (s, C5H5).    15. Substance 15: 16β- (ferrocenylmethyl) ethylamino-17α-hydroxy-3-methoxy-estra-1,3,5 (10) -triene formula 1 with a = 0, R = 17α-hydroxy-3-
    Methoxy-estra-1,3,5 (10) -triene-16β-yl, R 1 = C 2 H 5 , R 2 , R 4 = H, R 3 with x = 0 and R 6 = ferrocenyl, C 31 H 41 FeNO 2 (515.52),
    obtained by reacting 16β- (ferrocenylmethyl) amino-17α-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and C 2 H 5 I.
    Yield: 80.6% of theory. Th., MS (EI): 527 [M] + (isotopic pattern of Fe).
    Calculated:
    C 72.23, H 8.02, N 2.72;
    Found:
    C 71.34, H 7.90, N 2.93%.
    1 H NMR (CDCl 3 ): δ = 0.852 (s, 3H, 18-CH 3 ); 1,001 (t, 3 J (HH) = 7.1 Hz, 3H, CH 2 C H 3 ); 2,549 (q, 3 J (HH) = 7.1 Hz, 2H, C H 2 CH 3 ); 3,758 (s, 3H, OCH 3 ); 4.086 (s, 5H, C 5 H 5); 4,173 (m, 2H, C 5 H 4 ); 4,262 (m, 2H, C 5 H 4 ). 13 C NMR (CDCl 3 ): δ = 11.04 (s, CH 2 C H 3 ); 43.38 (s, C H 2 CH 3); 68.30 (s, C 5 H 5 ).
  • 16. Substanz 16: 3α-(Ferrocenylmethyl)acetamido-5α-cholestan Formel 1 mit a = 0, R = 5α-cholestan-3α-yl, R1 = Acyl, R2, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl, C40H61FeNO (627.78),
    erhalten durch Umsetzung von 3α-(Ferrocenylmethyl)amino-5α-cholestan und Acetanhydrid.
    Ausbeute: 74.8% d. Th., gelber Feststoff.
    Berechnet:
    C 76.53, H 9.79, N 2.23;
    Gefunden:
    C 76.41, H 9.87, N 2.12%.
    1H-NMR(CDCl3): δ = 2.146 (s, (br.), 3H, COCH3); 4.054 (m, 2H, C5H4); 4.118 (s, 5H, C5H5); 4.211 (m, 2H, C5H4).
    13C-NMR(CDCl3): δ = 67.56 (s, C5H4); 67.57 (s, C5H5); 86.36 (s, C5H4).    16. Substance 16: 3α- (ferrocenylmethyl) acetamido-5α-cholestan formula 1 with a = 0, R = 5α-cholestan-3α-yl, R 1 = acyl, R 2 , R 4 = H, R 3 with x = 0 and R 6 = ferrocenyl, C 40 H 61 FeNO (627.78),
    obtained by reacting 3α- (ferrocenylmethyl) amino-5α-cholestan and acetic anhydride.
    Yield: 74.8% of theory. Th., Yellow solid.
    Calculated:
    C 76.53, H 9.79, N 2.23;
    Found:
    C 76.41, H 9.87, N 2.12%.
    1 H NMR (CDCl 3 ): δ = 2,146 (s, (br.), 3H, COCH 3 ); 4,054 (m, 2H, C 5 H 4 ); 4,118 (s, 5H, C 5 H 5 ); 4,211 (m, 2H, C 5 H 4 ).
    13 C NMR (CDCl 3 ): δ = 67.56 (s, C 5 H 4 ); 67.57 (s, C 5 H 5); 86.36 (s, C 5 H 4 ).
  • 17. Substanz 17: 3α-(Ferrocenylmethyl)amino-2ß-hydroxy-5α-cholestan Formel 1 mit a = 0, R = 2ß-Hydroxy-5α-cholestan-3α-yl, R1, R2, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl, C38H60ClFeNO (638.20),
    erhalten durch Umsetzung von 3α-Amino-2ß-hydroxy-5α-cholestan, Ferrocencarbaldehyd und NaBH4.
    Ausbeute: 65.1% d. Th., gelbe Kristalle, Fp. 212-213°C (Zersetzg.). MS (DCI + H2O): 601[M-Cl]+ (isotopic pattern of Fe).
    Berechnet:
    C 71.52, H 9.48, N 2.19, Cl 5.56;
    Gefunden:
    C 70.90, H 9.72, N 2.19, Cl 5.65%.
    1H-NMR(CDCl3): δ = 4.162 (s, 5H, C5H5); 4.220 (m, 2H, C5H4); 4.398 (m, 2H, C5H4).
    13C-NMR(CDCl3): δ = 69.00 (s, C5H5); 69.81 (s, C5H4); 69.38 (s, C5H4).    17. Substance 17: 3α- (ferrocenylmethyl) amino-2ß-hydroxy-5α-cholestan formula 1 with a = 0, R = 2ß-hydroxy-5α-cholestan-3α-yl, R 1 , R 2 , R 4 = H , R 3 with x = 0 and R 6 = ferrocenyl, C 38 H 60 ClFeNO (638.20),
    obtained by reacting 3α-amino-2ß-hydroxy-5α-cholestan, ferrocenecarbaldehyde and NaBH 4 .
    Yield: 65.1% of theory. Th., Yellow crystals, mp 212-213 ° C (decomp.). MS (DCI + H 2 O): 601 [M-Cl] + (isotopic pattern of Fe).
    Calculated:
    C 71.52, H 9.48, N 2.19, Cl 5.56;
    Found:
    C 70.90, H 9.72, N 2.19, Cl 5.65%.
    1 H NMR (CDCl 3 ): δ = 4,162 (s, 5H, C 5 H 5 ); 4,220 (m, 2H, C 5 H 4 ); 4.398 (m, 2H, C 5 H 4).
    13 C NMR (CDCl 3 ): δ = 69.00 (s, C 5 H 5 ); 69.81 (s, C 5 H 4); 69.38 (s, C 5 H 4 ).
  • 18. Substanz 18: 3α-(Ferrocenylmethyl)amino-5α-cholestan Formel 1 mit a = 0, R = 5α-Cholestan-3α-yl, R1, R2, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl, C38H59FeN . 0.5H2O (594.74),
    erhalten durch Umsetzung von 3 α-Amino-5α-cholestan, Ferrocen­ carbaldehyd und NaBH4.
    Ausbeute: 74.8% d. Th., gelber Feststoff, Fp. 103-105°C. MS (EI): 585 [M- 0.5H2O]+ (isotopic pattern of Fe).
    Berechnet:
    C 76.74, H 10.17, N 2.36;
    Gefunden:
    C 76.47, H 10.13, N 2.35%.
    1H-NMR (CDCl3): δ = 2.850 (m, 1H, NH); 3.443 (s, 2H, N-CH2); 4.069 (m, 2H, C5H4); 4.101 (s, 5H, C5H5); 4.159 (m, 2H, C5H4).
    13C-NMR(CDCl3): δ = 46.26 (s, N-CH2); 67.56 (s, C5H4); 68.36 (s (überlagert), C5H4/C5H5); 87.86 (s, C5H4).    18. Substance 18: 3α- (ferrocenylmethyl) amino-5α-cholestan formula 1 with a = 0, R = 5α-cholestan-3α-yl, R 1 , R 2 , R 4 = H, R 3 with x = 0 and R 6 = ferrocenyl, C 38 H 59 FeN. 0.5H 2 O (594.74),
    obtained by reacting 3 α-amino-5α-cholestan, ferrocene carbaldehyde and NaBH 4 .
    Yield: 74.8% of theory. Th., Yellow solid, mp. 103-105 ° C. MS (EI): 585 [M-0.5H 2 O] + (isotopic pattern of Fe).
    Calculated:
    C 76.74, H 10.17, N 2.36;
    Found:
    C 76.47, H 10.13, N 2.35%.
    1 H NMR (CDCl 3 ): δ = 2,850 (m, 1H, NH); 3.443 (s, 2H, N-CH2); 4.069 (m, 2H, C 5 H 4); 4,101 (s, 5H, C 5 H 5 ); 4,159 (m, 2H, C 5 H 4 ).
    13 C NMR (CDCl 3 ): δ = 46.26 (s, N-CH 2 ); 67.56 (s, C 5 H 4); 68.36 (s (overlaid), C 5 H 4 / C 5 H 5 ); 87.86 (s, C 5 H 4 ).
  • 19. Substanz 19: 16α-(Ferrocenylmethyl)amino-17α-hydroxy-3-methoxy­ estra-1,3,5(10)-trien Formel 1 mit a = 0, R = 17α-Hydroxy-3-methoxy-estra- 1,3,5(10)-trien-16α-yl, R1, R2, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl, C30H37FeNO2 (499.55),
    erhalten durch Umsetzung von 16α-Amino-17α-hydroxy-3-methoxy-estra- 1,3,5(10)-trien mit Ferrocencarbaldehyd und anschließender in situ- Reduktion mit NaBH4.
    Ausbeute: 84% d. Th., goldockerfarbener amorpher Feststoff, Fp. 129-133°C (Methanol/Wasser). MS(EI): 499[M]+ (isotopic pattern of Fe), [α]D = +24°(CHCl3, c = 6.649).
    Berechnet:
    C 72.44, H 7.09, N 2.82;
    Gefunden:
    C 71.94, H 7.30, N 2.87%.
    1H-NMR(CDCl3): δ = 0.717 (s, 3H, 18-CH3); 2.817 (m, 2H, 6-CH2); 3.39-3.53 (m, überlagert, 4H, N-CH2, 16-, 17-H); 3.751 (s, 3H, OCH3); 4.117 (s, m, überlagert, 7H, C5H5, C5H4); 4.185 (m, 2H, C5H4); 6.508 (m, 1H, 4-CH); 6.685 (m, 1H, 2-CH); 7.205 (m, 1H, 1-CH).    19. Substance 19: 16α- (ferrocenylmethyl) amino-17α-hydroxy-3-methoxy estra-1,3,5 (10) -triene formula 1 with a = 0, R = 17α-hydroxy-3-methoxy-estra- 1,3,5 (10) -triene-16α-yl, R 1 , R 2 , R 4 = H, R 3 with x = 0 and R 6 = ferrocenyl, C 30 H 37 FeNO 2 (499.55),
    obtained by reacting 16α-amino-17α-hydroxy-3-methoxy-estra-1,3,5 (10) -triene with ferrocenecarbaldehyde and subsequent reduction in situ with NaBH 4 .
    Yield: 84% of theory Th., Gold ocher-colored amorphous solid, mp. 129-133 ° C (methanol / water). MS (EI): 499 [M] + (isotopic pattern of Fe), [α] D = + 24 ° (CHCl 3 , c = 6,649).
    Calculated:
    C 72.44, H 7.09, N 2.82;
    Found:
    C 71.94, H 7.30, N 2.87%.
    1 H NMR (CDCl 3 ): δ = 0.717 (s, 3H, 18-CH 3 ); 2.817 (m, 2H, 6-CH 2); 3.39-3.53 (m, overlaid, 4H, N-CH 2 , 16-, 17-H); 3,751 (s, 3H, OCH 3 ); 4,117 (s, m, overlaid, 7H, C 5 H 5 , C 5 H 4 ); 4,185 (m, 2H, C 5 H 4 ); 6.508 (m, 1H, 4-CH); 6,685 (m, 1H, 2-CH); 7.205 (m, 1H, 1-CH).
  • 20. Substanz 20 : 16β-(Ferrocenylmethyl)amino-17β-hydroxy-3-methoxy­ estra-1,3,5(10)-trien Formel 1 mit a = 0, R = 17β-Hydroxy-3-methoxy-estra- 1,3,5(10)-trien-16β-yl, R1, R2, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl, C30H37FeNO2 (499.55),
    erhalten durch Umsetzung von 16β-Amino-17β-hydroxy-3-methoxy-estra- 1,3,5(10)-trien mit Ferrocencarbaldehyd und anschließender in situ- Reduktion mit NaBH4.
    Ausbeute: 78% d. Th., feine goldgelbe Nadeln, Fp. 166-168°C (Essigester/Hexan). [α]D = +91° (CHCl3, c = 10.409).
    Berechnet:
    C 72.44, H 7.09, N 2.82;
    Gefunden:
    C 71.28, H 7.19, N 2.86%.
    1H-NMR(CDCl3): δ = 0.679 (s, 3H, 18-CH3); 2.822 (m, 2H, 6-CH2); 3.131 (m, 1H, 16-CH); 3.395(d, J4 = 8.8 Hz, 1H, 17-CH); 3.544 (s, 2H, N-CH2); 3.751 (s, 3H, OCH3); 4.108 (s, 5H, C5H5); 4.163 (m, 2H, C5H4); 4.189 (m, 2H, C5H4); 6.602 (m, 1H, 4-CH); 6.688 (m, 1H, 2-CH); 7.103(d, J4 = 8.62 Hz, 1H, 1-CH).    20. Substance 20: 16β- (ferrocenylmethyl) amino-17β-hydroxy-3-methoxy estra-1,3,5 (10) -triene formula 1 with a = 0, R = 17β-hydroxy-3-methoxy-estra- 1,3,5 (10) -triene-16β-yl, R 1 , R 2 , R 4 = H, R 3 with x = 0 and R 6 = ferrocenyl, C 30 H 37 FeNO 2 (499.55),
    obtained by reacting 16β-amino-17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene with ferrocenecarbaldehyde and subsequent reduction in situ with NaBH 4 .
    Yield: 78% of theory Th., Fine golden yellow needles, mp. 166-168 ° C (ethyl acetate / hexane). [α] D = + 91 ° (CHCl 3 , c = 10,409).
    Calculated:
    C 72.44, H 7.09, N 2.82;
    Found:
    C 71.28, H 7.19, N 2.86%.
    1 H NMR (CDCl 3 ): δ = 0.679 (s, 3H, 18-CH 3 ); 2.822 (m, 2H, 6-CH 2); 3,131 (m, 1H, 16-CH); 3,395 (d, J 4 = 8.8 Hz, 1H, 17-CH); 3.544 (s, 2H, N-CH2); 3,751 (s, 3H, OCH 3 ); 4,108 (s, 5H, C 5 H 5 ); 4,163 (m, 2H, C 5 H 4 ); 4,189 (m, 2H, C 5 H 4 ); 6,602 (m, 1H, 4-CH); 6,688 (m, 1H, 2-CH); 7.103 (d, J 4 = 8.62 Hz, 1H, 1-CH).
  • 21. Substanz 21: 16β-[(3,5-Di-tert-butyl-2-hydroxy)phenylmetyl]amino-17α- hydroxy-3-methoxy-estra-1,3,5(10)-trien Formel 1 mit a = 0, R = 17α- Hydroxy-3-methoxy-estra-1,3,5(10)-trien-16β-yl, R1, R2, R4 = H, R3 mit x = 0 und R6 = 3,5-Di-tert-butyl-2-hydroxyphenyl; C34H49NO3 (519.54), erhalten durch Umsetzung von 16β-(3,5-Di-tert-butylsalicylaldimino)-17α- hydroxy-3-methoxy-estra-1,3,5(10)-trien und NaBH4.
    Ausbeute: 82% d. Th., farblose Stäbchen, Fp. 182-184°C (Methanol). MS (EI): 519[M]+.
    Berechnet:
    C 78.60, H 9.51, N 2.70;
    Gefunden:
    C 77.67, H 9.33, N 2.83%.
    1H-NMR(CDCl3): δ = 0.885 (s, 3H, 18-CH3); 1.284 (s, 9H, tert-C4H9); 1.415 (s, 9H, tert-C4H9); 2.852 (m, 2H, 6-CH2); 3.041(dd = t, J4 = J5 7.9 Hz, 1H, 16α-H); 3.695 (s, 1H, 17β-H); 3.771 (s, 3H, OCH3); 3.999 (s, 2H, N-CH2); 6.633 (m, 1H, 4-CH); 6.713(dd, J4 = 8.64 Hz, J5 = 2.68 Hz, 1H, 2-CH); 6.907(d, J5 = 2.22 Hz, 1H, Ar-H); 7.212-7.234 (2d, überlagert, 2H, 1-CH und 6'-CH).
    13C-NMR(CDCl3): δ = 53.03 (s, N-Cl2); 68.29 (s, 16-C); 84.77 (s, 17-C).    21. Substance 21: 16β - [(3,5-di-tert-butyl-2-hydroxy) phenylmetyl] amino-17α-hydroxy-3-methoxy-estra-1,3,5 (10) -triene formula 1 with a = 0, R = 17α-hydroxy-3-methoxy-estra-1,3,5 (10) -trien-16β-yl, R 1 , R 2 , R 4 = H, R 3 with x = 0 and R6 = 3,5-di-tert-butyl-2-hydroxyphenyl; C 34 H 49 NO 3 (519.54), obtained by reacting 16β- (3,5-di-tert-butylsalicylaldimino) -17α-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and NaBH 4th
    Yield: 82% of theory Th., Colorless sticks, mp. 182-184 ° C (methanol). MS (EI): 519 [M] + .
    Calculated:
    C 78.60, H 9.51, N 2.70;
    Found:
    C 77.67, H 9.33, N 2.83%.
    1 H NMR (CDCl 3 ): δ = 0.885 (s, 3H, 18-CH 3 ); 1.284 (s, 9H, tert-C 4 H 9); 1.415 (s, 9H, tert-C 4 H 9); 2.852 (m, 2H, 6-CH 2); 3,041 (dd = t, J 4 = J 5 7.9 Hz, 1H, 16α-H); 3,695 (s, 1H, 17β-H); 3,771 (s, 3H, OCH 3 ); 3.999 (s, 2H, N-CH2); 6,633 (m, 1H, 4-CH); 6,713 (dd, J 4 = 8.64 Hz, J 5 = 2.68 Hz, 1H, 2-CH); 6,907 (d, J 5 = 2.22 Hz, 1H, Ar-H); 7.212-7.234 (2d, superimposed, 2H, 1-CH and 6'-CH).
    13 C NMR (CDCl 3 ): δ = 53.03 (s, N-Cl 2 ); 68.29 (s, 16-C); 84.77 (s, 17-C).
  • 22. Substanz 22: 15α-(Ferrocenylmethyl)amino-14β,17β-dihydroxy-3- methoxy-estra-1,3,5(10)-trien Formel 1 mit a = 0, R = 14β,17β-Dihydroxy-3- methoxy-estra-1,3,5(10)-trien-15α-yl, R1, R2, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl, C30H37FeNO3 (515.47),
    erhalten durch Umsetzung von 15α-Amino-14β,17β-dihydroxy-3-methoxy­ estra-1,3,5(10)-trien und NaBH4.
    Ausbeute: 48% d. Th., gelbe Kristalle, Fp. 163-166°C. [α]D = +11° (CHCl3, c = 10.96).
    Berechnet:
    C 69.90, H 7.23, N 2.72;
    Gefunden:
    C 70.04, H 7.37, N 2.79%.
    1H-NMR (CDCl3): δ = 1.098 (s, 3H, 18-CH3); 3.771 (s, 3H, OCH3); 3.862 (t, 1H, 17-CH); 4.08-4.14 (m, 9H, C5H5, C5H4).
    13C-NMR(CDCl3): δ = 14.09 (s, 18-CH3); 48.56 (s, N-CH2); 55.18 (s, OCH3); 68.92 (s, 15-C); 81.95 (s, 17-C).     22. Substance 22: 15α- (ferrocenylmethyl) amino-14β, 17β-dihydroxy-3-methoxy-estra-1,3,5 (10) -triene formula 1 with a = 0, R = 14β, 17β-dihydroxy-3 - methoxy-estra-1,3,5 (10) -triene-15α-yl, R 1 , R 2 , R 4 = H, R 3 with x = 0 and R 6 = ferrocenyl, C 30 H 37 FeNO 3 ( 515.47),
    obtained by reacting 15α-amino-14β, 17β-dihydroxy-3-methoxy estra-1,3,5 (10) -triene and NaBH 4 .
    Yield: 48% of theory Th., Yellow crystals, mp 163-166 ° C. [α] D = + 11 ° (CHCl 3 , c = 10.96).
    Calculated:
    C 69.90, H 7.23, N 2.72;
    Found:
    C 70.04, H 7.37, N 2.79%.
    1 H NMR (CDCl 3 ): δ = 1,098 (s, 3H, 18-CH 3 ); 3,771 (s, 3H, OCH 3 ); 3,862 (t, 1H, 17-CH); 4.08-4.14 (m, 9H, C 5 H 5 , C 5 H 4 ).
    13 C NMR (CDCl 3 ): δ = 14.09 (s, 18-CH 3 ); 48.56 (s, N-CH 2); 55.18 (s, OCH 3 ); 68.92 (s, 15-C); 81.95 (s, 17-C).
  • 23. Substanz 23: 16α-(Ferrocenylmethyl)amino-17β-hydroxy-3-methoxy­ estra-1,3,5(10)-trien . HCl Formel 1 mit a = 1, R = 17β-Hydroxy-3-Methoxy­ estra-1,3,5(10)-trien-16α-yl, R1, R2, R4, R5 = H, R3 mit x = 0 und R6 = Ferrocenyl, A = Cl, C30H38ClFeNO2 (535.96),
    erhalten durch Umsetzung von 16α-(Ferrocenylmethyl)amino-17β-hydroxy- 3-methoxy-estra-1,3,5(10)-trien und NH4Cl.
    Ausbeute: 74% d. Th., gelber Feststoff, Fp. 180-185°C (Zersetzung).
    Berechnet:
    C 67.23, H 7.15, N 2.61;
    Gefunden:
    C 68.38, H 7.21, N 2.60%.
    1H-NMR(CDCl3): δ = 0.774 (s, 3H, 18-CH3); 2.819 (m, 2H, 6-CH2); 3.113 (dd, J4 = 12.1 Hz, J5 = 5.8 Hz, 1H, 16-CH); 3.631(d, J4 = 13.3 Hz, 1H, 17-CH); 3.67-3.78(dd, überlagert, 2H, N-CH2); 3.751 (s, überlagert, 3H, OCH3); 4.14-4.17 (s, m, überlagert, 7H, C5H5, C5H4); 4.265 (s, 1H, C5H4); 4.346 (s, 1H, C5H4); 6.600 (m, 1H, 4-CH); 6.683 (dd, J4 = 8.56 Hz, J5 = 2.51 Hz, 1H, 2-CH); 7.163(d, J4 = 8.62 Hz, 1H, 1-CH).    23. Substance 23: 16α- (ferrocenylmethyl) amino-17β-hydroxy-3-methoxy estra-1,3,5 (10) -triene. HCl Formula 1 with a = 1, R = 17β-hydroxy-3-methoxy estra-1,3,5 (10) -trien-16α-yl, R 1 , R 2 , R 4 , R 5 = H, R 3 with x = 0 and R 6 = ferrocenyl, A = Cl, C 30 H 38 ClFeNO 2 (535.96),
    obtained by reacting 16α- (ferrocenylmethyl) amino-17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and NH 4 Cl.
    Yield: 74% of theory Th., Yellow solid, mp. 180-185 ° C (decomposition).
    Calculated:
    C 67.23, H 7.15, N 2.61;
    Found:
    C 68.38, H 7.21, N 2.60%.
    1 H NMR (CDCl 3 ): δ = 0.774 (s, 3H, 18-CH 3 ); 2.819 (m, 2H, 6-CH 2); 3,113 (dd, J 4 = 12.1 Hz, J 5 = 5.8 Hz, 1H, 16-CH); 3,631 (d, J 4 = 13.3 Hz, 1H, 17-CH); 3.67-3.78 (dd, overlaid, 2H, N-CH 2 ); 3,751 (s, overlaid, 3H, OCH 3 ); 4.14-4.17 (s, m, overlaid, 7H, C 5 H 5 , C 5 H 4 ); 4.265 (s, 1H, C 5 H 4); 4.346 (s, 1H, C 5 H 4); 6,600 (m, 1H, 4-CH); 6,683 (dd, J 4 = 8.56 Hz, J 5 = 2.51 Hz, 1H, 2-CH); 7.163 (d, J 4 = 8.62 Hz, 1H, 1-CH).
  • 24. Substanz 24: 15β-(Ferrocenylmethyl)amino-14α,17 β-dihydroxy-3- methoxy-estra-1,3,5(10)-trien Formel 1 mit a = 0, R = 14α,17β-Dihydroxy- 3-methoxy-estra-1,3,5(10)-trien-15β-yl, R1, R2, R4 = H, R3 mit x = 0 und R6 = Ferrocenyl, C30H37FeNO3 (515.47),
    erhalten durch Umsetzung von 15β-Amino-14α,17β-dihydroxy-3-methoxy­ estra-1,3,5(10)-trien mit Ferrocencarbaldehyd und anschließender in situ- Reduktion mit NaBH4.
    Ausbeute: 55.1% d. Th., gelbe Kristalle, Fp. 144-148°C. MS(EI): 515[M]+. 1H-NMR (CDCl3): δ = 0.869 (s, 3H, 18-CH3); 3.407(d, 3J = 13.2 Hz, 2H, N-CH2); 3.757 (s, 3H, OCH3); 4.05-4.16 (m, 9H, C5H5, C5H4).
    13C-NMR(CDCl3): δ = 15.23 (s, 18-CH3); 55.18 (s, OCH3).     24. Substance 24: 15β- (ferrocenylmethyl) amino-14α, 17 β-dihydroxy-3-methoxy-estra-1,3,5 (10) -triene formula 1 with a = 0, R = 14α, 17β-dihydroxy- 3-methoxy-estra-1,3,5 (10) -trien-15β-yl, R 1 , R 2 , R 4 = H, R 3 with x = 0 and R 6 = ferrocenyl, C 30 H 37 FeNO 3 (515.47),
    obtained by reacting 15β-amino-14α, 17β-dihydroxy-3-methoxy estra-1,3,5 (10) -triene with ferrocenecarbaldehyde and subsequent in situ reduction with NaBH 4 .
    Yield: 55.1% of theory. Th., Yellow crystals, mp 144-148 ° C. MS (EI): 515 [M] + . 1 H NMR (CDCl 3 ): δ = 0.869 (s, 3H, 18-CH 3 ); 3,407 (d, 3 J = 13.2 Hz, 2H, N-CH 2 ); 3,757 (s, 3H, OCH 3 ); 4.05-4.16 (m, 9H, C 5 H 5 , C 5 H 4 ).
    13 C NMR (CDCl 3 ): δ = 15.23 (s, 18-CH 3 ); 55.18 (s, OCH 3 ).
  • 25. Substanz 25: 16β-(Pyrrolcarbaldimino)-17β-hydroxy-3-methoxy-estra- 1,3,5(10)-trien Formel 1 mit a = 0, R = 17β-hydroxy-3-methoxy-estra- 1,3,5(10)-trien-16β-yl, R1, R2 = Bindung, R4 = H, R3 mit x = 0 und R6 = Pyrrolyl, C24H30N2O2 (378.51),
    erhalten durch Umsetzung von 16β-Amino-17β-hydroxy-3-methoxy-estra- 1,3,5(10)-trien und Pyrrol-2-carbaldehyd.
    Ausbeute: 76% d. Th., farblose Nadeln, Fp. 227-229°C (Zersetzung). [α]D = +11° (CHCl3, c = 7.640).
    Berechnet:
    C 76.16, H 7.99, N 7.40;
    Gefunden:
    C 76.29, H 8.02, N 7.19%.
    1H-NMR(CDCl3): δ = 0.873 (s, 3H, 18-CH3); 2.832 (m, 2H, 6-CH2); 3.669 (d, 4J = 8.64 Hz, 1H, 16-CH); 3.758 (s, 3H, OCH3); 3.912 (m, 1H, 17-CH); 6.258 (m, 1H, Ar-H); 6.545 (s, 1H, Ar-H); 6.610 (m, 1H, 4-CH); 6.952 (s, 1H, Ar-H); 7.203 (d, 4J = 8.55 Hz, 1H, 1-CH); 8.044 (s, 1H, CH=N).    25. Substance 25: 16β- (pyrrolecarbaldimino) -17β-hydroxy-3-methoxy-estra- 1,3,5 (10) -triene formula 1 with a = 0, R = 17β-hydroxy-3-methoxy-estra- 1,3,5 (10) -triene-16β-yl, R 1 , R 2 = bond, R 4 = H, R 3 with x = 0 and R 6 = pyrrolyl, C 24 H 30 N 2 O 2 (378.51 ),
    obtained by reacting 16β-amino-17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and pyrrole-2-carbaldehyde.
    Yield: 76% of theory Th., Colorless needles, mp. 227-229 ° C (decomposition). [α] D = + 11 ° (CHCl 3 , c = 7,640).
    Calculated:
    C 76.16, H 7.99, N 7.40;
    Found:
    C 76.29, H 8.02, N 7.19%.
    1 H NMR (CDCl 3 ): δ = 0.873 (s, 3H, 18-CH 3 ); 2.832 (m, 2H, 6-CH 2); 3,669 (d, 4 J = 8.64 Hz, 1H, 16-CH); 3,758 (s, 3H, OCH 3 ); 3,912 (m, 1H, 17-CH); 6,258 (m, 1H, Ar-H); 6,545 (s, 1H, Ar-H); 6,610 (m, 1H, 4-CH); 6,952 (s, 1H, Ar-H); 7,203 (d, 4 J = 8.55 Hz, 1H, 1-CH); 8,044 (s, 1H, CH = N).
  • 26. Substanz 26: 16β-(Thiophen-2-ylmethyl)amino-17β-hydroxy-3- methoxy-estra-1,3,5(10)-trien Formel 1 mit a = 0, R = 17β-hydroxy-3- methoxy-estra-1,3,5(10)-trien-16β-yl, R1, R2, R4 = H, R3 mit x = 0 und R6 = Thiophenyl, C24H32NO2S (397.57),
    erhalten durch Umsetzung von 16β-(Thiophencarbaldimino)-17β-hydroxy-3- methoxy-estra-1,3,5(10)-trien mit Thiophen-2-carbaldehyd und anschließen­ der in situ-Reduktion mit NaBH4.
    Ausbeute: 86% d. Th., farblose Nadeln, Fp. 105-108°C (Methanol), [α]D = +76°(CHCl3, c = 10.266).
    Berechnet:
    C 72.50, H 7.86, N 3.52, S 8.06;
    Gefunden:
    C 72.23, H 7.97, N 3.58, S 7.94%.
    1H-NMR (CDCl3): δ = 0.695 (s, 3H, 18-CH3); 2.832 (m, 2H, 6-CH2); 3.182 (m, 1H, 16-CH); 3.415 (d, 4J = 8.84 Hz, 1H, 17-CH); 3.759 (s, 3H, OCH3); 4.021 (dd, 3J = 25.46 Hz, 4J = 14.20 Hz, 2H, Ar-CH2); 6.610 (m, 1H, 4-CH); 6.696 (m, 1H, 2-CH); 6.94-6.96 (m, überlagert, 2H, Ar-H); 7.18-7.23 (m, überlagert, 2H, Ar-H, 1-CH).
    13C-NMR (CDCl3): δ = 48.58 (s, N-CH2); 57.09 (s, 16-C); 79.14 (s, 17-C).    26. Substance 26: 16β- (thiophene-2-ylmethyl) amino-17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene formula 1 with a = 0, R = 17β-hydroxy-3 - methoxy-estra-1,3,5 (10) -triene-16β-yl, R 1 , R 2 , R 4 = H, R 3 with x = 0 and R 6 = thiophenyl, C 24 H 32 NO 2 S (397.57),
    obtained by reacting 16β- (thiophenecarbaldimino) -17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene with thiophene-2-carbaldehyde and then in situ reduction with NaBH 4 .
    Yield: 86% of theory Th., Colorless needles, mp 105-108 ° C (methanol), [α] D = + 76 ° (CHCl 3 , c = 10.266).
    Calculated:
    C 72.50, H 7.86, N 3.52, S 8.06;
    Found:
    C 72.23, H 7.97, N 3.58, S 7.94%.
    1 H NMR (CDCl 3 ): δ = 0.695 (s, 3H, 18-CH 3 ); 2.832 (m, 2H, 6-CH 2); 3,182 (m, 1H, 16-CH); 3,415 (d, 4 J = 8.84 Hz, 1H, 17-CH); 3,759 (s, 3H, OCH 3 ); 4,021 (dd, 3 J = 25.46 Hz, 4 J = 14.20 Hz, 2H, Ar-CH 2 ); 6,610 (m, 1H, 4-CH); 6,696 (m, 1H, 2-CH); 6.94-6.96 (m, overlaid, 2H, Ar-H); 7.18-7.23 (m, overlaid, 2H, Ar-H, 1-CH).
    13 C NMR (CDCl 3 ): δ = 48.58 (s, N-CH 2 ); 57.09 (s, 16-C); 79.14 (s, 17-C).
  • 27. Substanz 27: 16α-(Thiophencarbaldimino)-17β-hydroxy-3-methoxy­ estra-1,3,5(10)-trien Formel 1 mit a = 0, R = 17β-hydroxy-3-methoxy-estra- 1,3,5(10)-trien-16α-yl, R1, R2 Bindung, R4 = H, R3 mit x = 0 und R6 = Thiophenyl, C24H29NO2S (395.50),
    erhalten durch Umsetzung von 16α-Amino-17β-hydroxy-3-methoxy-estra- 1,3,5(10)-trien und Thiophencarbaldehyd.
    Ausbeute: 78% d. Th., farblose Stäbchen, Fp. 191-193°C (Essigester/Heptan). [α]D = +80° (CHCl3, c = 9.328).
    Berechnet:
    C 72.88, H 7.39, N 3.54, S 8.11;
    Gefunden:
    C 72.46, H 7.48, N 3.58, S 8.26%.
    1H-NMR (CDCl3): δ = 0.886 (s, 3H, 18-CH3); 2.849 (m, 2H, 6-CH2); 3.622 (m, 1H, 16-CH); 3.63-3.77 (m, überlagert, 1H, 17-CH); 3.763 (s, überlagert, 3H, OCH3); 6.620 (m, 1H, 4-CH); 6.704 (dd, 4J = 8.56 Hz, 5J = 2.63 Hz 1H, 2-CH); 7.048 (m, 1H, Ar-H); 7.191 (d, 4J = 8.60 Hz, 1H 1-CH); 7.275 (d, 4J = 3.52 Hz, 1H, Ar-H); 7.346 (d, 4J = 3.52 Hz, 1H, Ar-H); 8.354 (s, 1H, CH=N).
    13C-NMR (CDCl3): δ = 48.58 (s, N-CH2); 57.09 (s, 16-C); 79.14 (s, 17-C).    27. Substance 27: 16α- (thiophenecarbaldimino) -17β-hydroxy-3-methoxy estra-1,3,5 (10) -triene formula 1 with a = 0, R = 17β-hydroxy-3-methoxy-estra-1 , 3,5 (10) -triene-16α-yl, R 1 , R 2 bond, R 4 = H, R 3 with x = 0 and R 6 = thiophenyl, C 24 H 29 NO 2 S (395.50),
    obtained by reacting 16α-amino-17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and thiophenecarbaldehyde.
    Yield: 78% of theory Th., Colorless sticks, mp. 191-193 ° C (ethyl acetate / heptane). [α] D = + 80 ° (CHCl 3 , c = 9,328).
    Calculated:
    C 72.88, H 7.39, N 3.54, S 8.11;
    Found:
    C 72.46, H 7.48, N 3.58, S 8.26%.
    1 H NMR (CDCl 3 ): δ = 0.886 (s, 3H, 18-CH 3 ); 2.849 (m, 2H, 6-CH 2); 3,622 (m, 1H, 16-CH); 3.63-3.77 (m, overlaid, 1H, 17-CH); 3,763 (s, overlaid, 3H, OCH 3 ); 6,620 (m, 1H, 4-CH); 6,704 (dd, 4 J = 8.56 Hz, 5 J = 2.63 Hz 1H, 2-CH); 7,048 (m, 1H, Ar-H); 7,191 (d, 4 J = 8.60 Hz, 1H 1-CH); 7,275 (d, 4 J = 3.52 Hz, 1H, Ar-H); 7,346 (d, 4 J = 3.52 Hz, 1H, Ar-H); 8,354 (s, 1H, CH = N).
    13 C NMR (CDCl 3 ): δ = 48.58 (s, N-CH 2 ); 57.09 (s, 16-C); 79.14 (s, 17-C).
  • 28. Substanz 28: 16β-(2-Methyl-3-hydroxy-5-hyroxymethyl-isonicotin­ aldimino)-17β-hydroxy-3-methoxy-estra-1,3,5(10)-trien Formel 1 mit a = 0, R = 17β-hydroxy-3-methoxy-estra-1,3,5(10)-trien-16β-yl, R1, R2 Bindung, R4 = H, R4 mit x = 0 und R6 = 4-(2-Methyl-3-hydroxy-5- hyroxymethyl)pyridyl, C27H34N2O4 (450.57),
    erhalten durch Umsetzung von 16β-Amino-17β-hydroxy-3-methoxy-estra- 1,3,5(10)-trien und 2-Methyl-3-hydroxy-5-hyroxymethyl-isonicotinaldehyd­ hydrochlorid.
    Ausbeute: 82% d. Th., feine gelbe Nadeln, Fp. 244-246°C (Zersetzung). MS (EI): 450 [M]+. [α]D = +61° (Pyridin, c = 9.509).
    Berechnet:
    C 71.98, H 7.61, N 6.22;
    Gefunden:
    C 72.09, H 7.34, N 6.28%.
    1H-NMR (DMSO-D6): δ = 0.845 (s, 3H, 18-CH3); 2.339 (s, 3H, Ar-CH3); 2.770 (m, 2H, 6-CH2); 2.335 (m, 1H, 16-CH); 3.667 (s, 3H, OCH3); 3.964 (m, 1H, 17-CH); 4.616 (m, 2H, Ar-CH 2-OH); 4.919 (s, 1H, 17-OH); 5.342 (m, 1H, Ar-CH2-OH); 6.593 (s, 1H, 4-CH); 6.666 (m, 1H, 2-CH); 7.163 (d, 4J = 8.64 Hz, 1H, 1-CH); 7.818 (s, 1H, Ar-H); 8.686 (s, 1H, CH=N); 14,799 (s, 1H, Ar-OH).    28. Substance 28: 16β- (2-methyl-3-hydroxy-5-hydroxymethyl-isonicotin aldimino) -17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene formula 1 with a = 0 , R = 17β-hydroxy-3-methoxy-estra-1,3,5 (10) -trien-16β-yl, R 1 , R 2 bond, R 4 = H, R 4 with x = 0 and R 6 = 4- (2-methyl-3-hydroxy-5-hydroxymethyl) pyridyl, C 27 H 34 N 2 O 4 (450.57),
    obtained by reacting 16β-amino-17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and 2-methyl-3-hydroxy-5-hyroxymethyl-isonicotinaldehyde hydrochloride.
    Yield: 82% of theory Th., Fine yellow needles, mp. 244-246 ° C (decomposition). MS (EI): 450 [M] + . [α] D = + 61 ° (pyridine, c = 9.509).
    Calculated:
    C 71.98, H 7.61, N 6.22;
    Found:
    C 72.09, H 7.34, N 6.28%.
    1 H NMR (DMSO-D 6 ): δ = 0.845 (s, 3H, 18-CH 3 ); 2.339 (s, 3H, Ar-CH3); 2.770 (m, 2H, 6-CH 2); 2,335 (m, 1H, 16-CH); 3.667 (s, 3H, OCH3); 3,964 (m, 1H, 17-CH); 4.616 (m, 2H, Ar-C H 2 -OH); 4,919 (s, 1H, 17-OH); 5,342 (m, 1H, Ar-CH 2 -O H ); 6,593 (s, 1H, 4-CH); 6,666 (m, 1H, 2-CH); 7,163 (d, 4 J = 8.64 Hz, 1H, 1-CH); 7,818 (s, 1H, Ar-H); 8,686 (s, 1H, CH = N); 14.799 (s, 1H, Ar-OH).
  • 29. Substanz 29: 16β-(2-Hydroxyphenylmethyl)amino-17α-hydroxy-3- methoxy-estra-1,3,5(10)-trien Formel 1 mit a = 0, R = 17α-Hydroxy-3- methoxy-estra-1,3,5(10)-trien-16β-yl, R1, R2, R4 = H, R3 mit x = 0 und R6 = 2- Hydroxyphenyl, C26H33NO3 (407.6),
    erhalten durch Umsetzung von 16β-[(E)-salicylidenimino]-17α-hydroxy-3- methoxy-estra-1,3,5(10)-trien und NaBH4.
    Ausbeute: 93.5% d. Th., farbloser Feststoff, Fp. 158-161°C.
    Berechnet:
    C 76.62, H 8.16, N 3.44;
    Gefunden:
    C 76.46, H 8.37, N 3.51%.
    1H-NMR (CDCl3): δ = 0.878 (s, 3H, 18-CH3); 3.030 (m, 1H, 16-CH); 3.697 (m, 1H, 17-CH); 3.760 (s, 3H, OCH3); 4.018 (s, 2H, N-CH 2); 6.62-7.21 (m, 7H, Ar-H).
    13C-NMR (CDCl3): δ = 51.99 (s, N-CH2); 116.42, 119.24, 128.23, 128.86 (C6H5); 122.77 (CH2-C 6H5); 157.96 (HO-C 6H5).     29. Substance 29: 16β- (2-hydroxyphenylmethyl) amino-17α-hydroxy-3-methoxy-estra-1,3,5 (10) -triene formula 1 with a = 0, R = 17α-hydroxy-3-methoxy -estra-1,3,5 (10) -triene-16β-yl, R 1 , R 2 , R 4 = H, R 3 with x = 0 and R 6 = 2-hydroxyphenyl, C 26 H 33 NO 3 ( 407.6),
    obtained by reacting 16β - [(E) -salicylidenimino] -17α-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and NaBH 4 .
    Yield: 93.5% of theory. Th., Colorless solid, mp 158-161 ° C.
    Calculated:
    C 76.62, H 8.16, N 3.44;
    Found:
    C 76.46, H 8.37, N 3.51%.
    1 H NMR (CDCl 3 ): δ = 0.878 (s, 3H, 18-CH 3 ); 3,030 (m, 1H, 16-CH); 3,697 (m, 1H, 17-CH); 3,760 (s, 3H, OCH 3 ); 4.018 (s, 2H, NC H 2); 6.62-7.21 (m, 7H, Ar-H).
    13 C NMR (CDCl 3 ): δ = 51.99 (s, N-CH 2 ); 116.42, 119.24, 128.23, 128.86 (C 6 H 5 ); 122.77 (CH 2 - C 6 H 5); 157.96 (HO- C 6 H 5 ).
  • 30. Substanz 30: 16α-(2-Methyl-3-hydroxy-5-hyroxymethyl-isonicotin­ aldimino)-17β-hydroxy-3-methoxy-estra-1,3,5(10)-trien Formel 1 mit a = 0, R = 17β-hydroxy-3-methoxy-estra-1,3,5(10)-trien-16α-yl, R1, R2 = Bindung, R4 = H, R3 mit x = 0 und R6 = 4-(2-Methyl-3-hydroxy-5- hyroxymethyl)pyridyl, C27H34N2O4(450.57),
    erhalten durch Umsetzung von 16α-Amino-17β-hydroxy-3-methoxy-estra- 1,3,5(10)-trien und 2-Methyl-3-hydroxy-5-hyroxymethyl-isonicotinaldehyd­ hydrochlorid und anschließender Behandlung mit einer 5%igen Kaliumcarbonatlösung.
    Ausbeute: 82% d. Th., gelbe Schuppen, Fp. 235-259°C (Zersetzung). MS (FAB/3-NBA): 451[M + 1]+. [α]D = +14°(Pyridin, c = 10.261).
    Berechnet:
    C 71.98, H 7.61, N 6.22;
    Gefunden:
    C 70.34, H 7.82, N 6.17%.
    1H-NMR (DMSO-D6): δ = 0.799 (s, 3H, 18-CH3); 2.367 (s, 3H, Ar-CH3); 2.768 (m, 2H, 6-CH2); 3.508 (m, 1H, 16-CH); 3.678 (s, überlagert, 4H, OCH3, 17-CH); 4.625 (m, 2H, Ar-CH 2-OH); 5.130 (s, 1H, 17-OH); 5.350 (s (breit), 1H, Ar-CH2-OH); 6.602 (s, 1H, 4-CH); 6.664 (m, 1H, 2-CH); 7.161 (d, 4J = 8.62 Hz, 1H, 1-CH); 7.893 (s, 1H, Ar-H); 8.797 (s, 1H, CH=N); 14.552 (s, 1H, Ar-OH).
    30. Substance 30: 16α- (2-methyl-3-hydroxy-5-hydroxymethyl-isonicotin aldimino) -17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene formula 1 with a = 0 , R = 17β-hydroxy-3-methoxy-estra-1,3,5 (10) -trien-16α-yl, R 1 , R 2 = bond, R 4 = H, R 3 with x = 0 and R 6 = 4- (2-methyl-3-hydroxy-5-hydroxymethyl) pyridyl, C 27 H 34 N 2 O 4 (450.57),
    obtained by reacting 16α-amino-17β-hydroxy-3-methoxy-estra-1,3,5 (10) -triene and 2-methyl-3-hydroxy-5-hyroxymethyl-isonicotinaldehyde hydrochloride and subsequent treatment with a 5% potassium carbonate solution.
    Yield: 82% of theory Th., Yellow scales, mp. 235-259 ° C (decomposition). MS (FAB / 3-NBA): 451 [M + 1] + . [α] D = + 14 ° (pyridine, c = 10,261).
    Calculated:
    C 71.98, H 7.61, N 6.22;
    Found:
    C 70.34, H 7.82, N 6.17%.
    1 H NMR (DMSO-D 6 ): δ = 0.799 (s, 3H, 18-CH 3 ); 2.367 (s, 3H, Ar-CH3); 2.768 (m, 2H, 6-CH 2); 3,508 (m, 1H, 16-CH); 3,678 (s, overlaid, 4H, OCH 3 , 17-CH); 4.625 (m, 2H, Ar-C H 2 -OH); 5,130 (s, 1H, 17-OH); 5,350 (s (broad), 1H, Ar-CH 2 -O H ); 6,602 (s, 1H, 4-CH); 6,664 (m, 1H, 2-CH); 7,161 (d, 4 J = 8.62 Hz, 1H, 1-CH); 7,893 (s, 1H, Ar-H); 8,797 (s, 1H, CH = N); 14,552 (s, 1H, Ar-OH).

Claims (2)

1. Estratrienderivate der allgemeinen Formel I
worin
R1 und R2 ein Wasserstoffatom oder eine Hydroxygruppe,
R3 oder R4 die Gruppen
und das Symbol die α- oder β-Stellung bedeuten. 1. Estratriene derivatives of the general formula I
wherein
R 1 and R 2 represent a hydrogen atom or a hydroxy group,
R 3 or R 4 the groups
and the symbol means the α or β position. 2. Cholestanderivate der allgemeinen Formel II
worin
R5 ein Wasserstoffatom oder eine Hydroxygruppe,
R6 die Gruppen
und das Symbol die α- oder β-Stellung bedeuten.2. Cholestane derivatives of the general formula II
wherein
R 5 represents a hydrogen atom or a hydroxy group,
R 6 the groups
and the symbol means the α or β position.
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* Cited by examiner, † Cited by third party
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