DE1011870B - Process for the preparation of the sodium salt of lactose triphosphoric acid ester - Google Patents
Process for the preparation of the sodium salt of lactose triphosphoric acid esterInfo
- Publication number
- DE1011870B DE1011870B DEF19377A DEF0019377A DE1011870B DE 1011870 B DE1011870 B DE 1011870B DE F19377 A DEF19377 A DE F19377A DE F0019377 A DEF0019377 A DE F0019377A DE 1011870 B DE1011870 B DE 1011870B
- Authority
- DE
- Germany
- Prior art keywords
- lactose
- sodium salt
- acid ester
- preparation
- triphosphoric acid
- 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.)
- Pending
Links
- 159000000000 sodium salts Chemical class 0.000 title claims description 10
- -1 lactose triphosphoric acid ester Chemical class 0.000 title claims description 6
- 238000000034 method Methods 0.000 title claims description 6
- 238000002360 preparation method Methods 0.000 title claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 6
- 239000008101 lactose Substances 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 2
- CZMRCDWAGMRECN-UHFFFAOYSA-N 2-{[3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy}-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound OCC1OC(CO)(OC2OC(CO)C(O)C(O)C2O)C(O)C1O CZMRCDWAGMRECN-UHFFFAOYSA-N 0.000 claims 1
- 150000004676 glycans Chemical class 0.000 claims 1
- 229920001282 polysaccharide Polymers 0.000 claims 1
- 239000005017 polysaccharide Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 description 4
- 235000011941 Tilia x europaea Nutrition 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000004571 lime Substances 0.000 description 4
- 150000003014 phosphoric acid esters Chemical class 0.000 description 4
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 3
- 230000002402 anti-lipaemic effect Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 210000002381 plasma Anatomy 0.000 description 3
- 150000003839 salts Chemical class 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 229940077731 carbohydrate nutrients Drugs 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000001000 lipidemic effect Effects 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 159000000009 barium salts Chemical class 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229960002737 fructose Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H11/00—Compounds containing saccharide radicals esterified by inorganic acids; Metal salts thereof
- C07H11/04—Phosphates; Phosphites; Polyphosphates
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verfahren zur Herstellung des Natriumsalzes des Lactosetriphosphorsäureesters Die Erfindung betrifft die Herstellung des Natriumsalzes des Lactosetriphosphorsäureesters durch Einwirkung von Phosphoroxychlorid auf Lactose bei Anwesenheit von Pyridin und spätere Neutralisation mit Natronlauge.Process for the preparation of the sodium salt of the lactose triphosphoric acid ester The invention relates to the preparation of the sodium salt of the lactose triphosphoric acid ester by the action of phosphorus oxychloride on lactose in the presence of pyridine and subsequent neutralization with sodium hydroxide solution.
Erfindungsgemäß wird so vorgegangen, daß man das Phosphoroxychlorid bei Temperaturen unterhalb 0° auf die Lactose bei Anwesenheit von Pyridin einwirken läßt, die Temperatur dann auf etwa 0° erhöht und die Mischung bei dieser Temperatur längere Zeit verweilen läßt, worauf unter ständigem Rühren das Reaktionsgemisch erwärmt und das Pyridin durch Destillation unter Vakuum entfernt wird. Der Trockenrückstand wird sodann mit Eis aufgenommen, mit Natronlauge neutralisiert und schließlich filtriert. Das so gewonnene Natriumsalz des Esters wird mit Alkohol gefällt und gegen fließendes Wasser dialysiert, worauf sich eine nochmalige Fällung und Trocknung unter Vakuum anschließt.According to the invention, the procedure is that the phosphorus oxychloride act on the lactose at temperatures below 0 ° in the presence of pyridine leaves, the temperature is then increased to about 0 ° and the mixture at this temperature Can linger for a long time, whereupon the reaction mixture is stirred continuously heated and the pyridine is removed by distillation under vacuum. The dry residue is then taken up with ice, neutralized with sodium hydroxide solution and finally filtered. The sodium salt of the ester obtained in this way is precipitated with alcohol and against flowing Dialyzed water, followed by repeated precipitation and drying under vacuum connects.
Es sind Verfahren zur Herstellung von Phosphorsäureestern der Kohlenhydrate und mehrwertigen Alkohole bereits bekanntgeworden, die darin bestehen,. daß man diese mit Phosphorpentoxyd in Gegenwart von tertiären Basen behandelt, während man nach noch älteren Vorschlägen die Phosphorsäureester der Kohlenhydrate und mehrwertigen Alkohole dergestalt gewann, daß man Phosphoroxychlorid auf die wäßrigen Lösungen von Glucose oder Rohrzucker in Gegenwart von Kalk oder Kreide einwirken ließ. Man erhält so das in Alkohol unlösliche Kalksalz des Phosphorsäureesters, das man dann aus der konzentrierten Reaktionsflüssigkeit mit Alkohol ausfällen muß. Dieses Kalksalz ist mit großen Mengen Chlorcalcium verunreinigt, die man nur durch wiederholtes Ausfällen und Waschen mit Alkohol entfernen kann.There are processes for the production of phosphoric acid esters of carbohydrates and polyhydric alcohols already become known, which consist in it. that he these treated with phosphorus pentoxide in the presence of tertiary bases, while one according to even older proposals, the phosphoric acid esters of carbohydrates and polyvalent ones Alcohols were obtained by adding phosphorus oxychloride to the aqueous solutions let act of glucose or cane sugar in the presence of lime or chalk. Man the lime salt of the phosphoric acid ester, which is insoluble in alcohol, is obtained in this way must precipitate from the concentrated reaction liquid with alcohol. This lime salt is contaminated with large amounts of calcium chloride, which can only be obtained by repeating it Can remove precipitating and washing with alcohol.
Bei Lävulose, Milchzucker und Maltose ist die Entfernung des Chlorcalciums jedoch praktisch unmöglich, da sich beständig Verbindungen des Phosphorsäureesters und des Chlorcalciums bilden. Demgegenüber wird nach der neuen Arbeitsweise das Natriumsalz des Lactosetriphosphorsäureesters gewonnen, das löslicher und weniger giftig ist als das entsprechende Kalksalz.In the case of levulose, milk sugar and maltose, the removal of calcium chloride is essential but practically impossible because there are constant compounds of the phosphoric acid ester and calcium chloride form. In contrast, according to the new way of working, the Sodium salt of the lactose triphosphoric acid ester obtained, the more soluble and less is more poisonous than the corresponding lime salt.
Das bereits ebenfalls dargestellte entsprechende Bariumsalz ist therapeutisch wegen seiner Giftigkeit völlig unbrauchbar.The corresponding barium salt already shown is therapeutic completely unusable because of its toxicity.
Ausführungsbeispiel 1 kg Lactose vom Schmelzpunkt 211° wird während 12 Stunden unter Vakuum bei 80° getrocknet, hierauf sorgfältig vor Feuchtigkeit geschützt in 101 wasserfreiem Pyridin unter Rühren suspendiert und sodann diese Suspension auf -30° abgekühlt. Hierauf läßt man langsam 0,5 1 Phosphoroxychlorid eintropfen und die Temperatur auf 0° ansteigen, bei welcher man die Mischung 90 Minuten lang beläßt. Sodann wird während 12 Stunden auf 40° unter Rühren erhitzt und das Pyridin unter Vakuum bei 60° bis zur Trockene abdestilliert, der Rückstand mit Eis aufgenommen, mit 40o/oiger Natronlauge neutralisiert, filtriert und das Natriumsalz mit Alkohol ausgefällt. Sodann dialysiert man 48 Stunden gegen fließendes Wasser, fällt nochmals aus und trocknet erneut im Vakuum bei 60°.Embodiment 1 kg of lactose with a melting point of 211 ° is used during Dried under vacuum at 80 ° for 12 hours, then carefully protected from moisture Suspended protected in 101 anhydrous pyridine with stirring and then this Suspension cooled to -30 °. Thereupon one leaves slowly 0.5 l of phosphorus oxychloride drop in and the temperature rise to 0 °, at which the mixture 90 Left for minutes. The mixture is then heated to 40 ° with stirring for 12 hours and the pyridine is distilled off under vacuum at 60 ° to dryness, the residue taken up with ice, neutralized with 40% sodium hydroxide solution, filtered and the Sodium salt precipitated with alcohol. Then dialyze against fluids for 48 hours Water, precipitates again and dries again in vacuo at 60 °.
Man gewinnt so in Form eines braunen, geruch-und geschmacklosen Pulvers das Natriumsalz des Lactosetriphosphorsäureesters mit einem Gehalt von 13,1% Phosphor, der Formel C12 Hls 0ll(Na2 P 03)3 entsprechend mit einem Molekulargewicht von 714,31.This is obtained in the form of a brown, odorless and tasteless powder the sodium salt of lactose triphosphoric acid ester with a content of 13.1% phosphorus, corresponding to the formula C12 Hls 0ll (Na2 P 03) 3 with a molecular weight of 714.31.
Dieser Ester, einem lipaemischen Tier eingespritzt, zeigt eine bedeutende antilipaemische Wirkung. Diese antilipaemische Wirkung zeigt sich auch durch einen Transmissionsprozentzuwachs am Spektrophotometer von Beckmann, nach der Technik Seifters arbeitend. Ein lipaemisches Hundeplasma wird mit Mausplasma gemischt, das mit dem Ester behandelt wurde, darauf in einem Thermostat bei 22° gehalten und dann auf dem Beckmann der Transmissionsprozentsatz im Augenblick der Vereinigung der beiden Plasmen und einige Stunden später abgelesen.This ester, injected into a lipemic animal, shows a significant one antilipaemic effect. This anti-lipaemic effect is also shown by a Transmission percentage increase on the Beckmann spectrophotometer, according to the technique Seifters working. A lipemic dog plasma is mixed with mouse plasma, the was treated with the ester, then kept in a thermostat at 22 ° and then on the Beckmann the percentage of transmission at the moment of the union of the both plasmas and read a few hours later.
Das Natriumsalz des Esters, das keine antikoagulierende Wirkung ausübt, ist das erste Syntheseprodukt, das wegen seiner antilipaemischen Wirkung zll Heilzwecken verwendet werden kann.The sodium salt of the ester, which has no anticoagulant effect, is the first synthetic product that, because of its anti-lipaemic effect, is used for healing purposes can be used.
Claims (1)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT1011870X | 1955-02-03 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1011870B true DE1011870B (en) | 1957-07-11 |
Family
ID=11429075
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEF19377A Pending DE1011870B (en) | 1955-02-03 | 1956-01-27 | Process for the preparation of the sodium salt of lactose triphosphoric acid ester |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE1011870B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1299290B (en) * | 1962-03-15 | 1969-07-17 | Colonial Sugar Refining Compan | Process for the preparation of salts of phosphoric acid esters of sugar or polyhydric alcohols |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE484356C (en) * | 1925-04-27 | 1929-10-19 | Ste Chim Usines Rhone | Process for the production of phosphoric acid esters of carbohydrates and polyhydric alcohols |
-
1956
- 1956-01-27 DE DEF19377A patent/DE1011870B/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE484356C (en) * | 1925-04-27 | 1929-10-19 | Ste Chim Usines Rhone | Process for the production of phosphoric acid esters of carbohydrates and polyhydric alcohols |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1299290B (en) * | 1962-03-15 | 1969-07-17 | Colonial Sugar Refining Compan | Process for the preparation of salts of phosphoric acid esters of sugar or polyhydric alcohols |
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