PL194401B1 - Method of obtaining androst-4-ene 3,17-dione - Google Patents
Method of obtaining androst-4-ene 3,17-dioneInfo
- Publication number
- PL194401B1 PL194401B1 PL347952A PL34795201A PL194401B1 PL 194401 B1 PL194401 B1 PL 194401B1 PL 347952 A PL347952 A PL 347952A PL 34795201 A PL34795201 A PL 34795201A PL 194401 B1 PL194401 B1 PL 194401B1
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- androst
- dione
- obtaining
- ene
- culture
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- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
1. Sposób otrzymywania androst-4-en- -3,17-dionu, o wzorze 2, z testosteronu, o wzo- rze 1, droga mikrobiologiczna, znamienny tym, ze substrat, poddaje sie biotransformacji z wy- korzystaniem kultury szczepu z gatunku Epithy- rium resinae. PL PL PL1. The method of obtaining androst-4-en-3,17-dione, formula 2, from testosterone, formula 1, by microbiological route, characterized in that the substrate is biotransformed using the culture of the strain of the species Epithyrium resinae. PL PL PL
Description
Opis wynalazkuDescription of the invention
Przedmiotem wynalazku jest sposób otrzymywania androst-4-en-3,17-dionu, o wzorze 2 przedstawionym na rysunku. Związek ten wykazuje działanie androgenne i może znaleźć zastosowanie w przemyśle farmaceutycznym.The subject of the invention is a method for the preparation of androst-4-ene-3,17-dione of formula 2 shown in the drawing. This compound has an androgenic effect and can be used in the pharmaceutical industry.
Znane są metody otrzymywania androst-4-en-3,17-dionu z testosteronu na drodze biotransformacji z wykorzystaniem systemów enzymatycznych drobnoustrojów (Atta-ur-Ra-hman, M. Iqbal Choudghary, Fahim Asif, Afgan Farooq, M. Yaqoob Nat. Prod. Lett. 12/4, ss. 255-261, 1998 oraz Cabeza Marisa S., Gutierrez Edgar B., Garcia Genoveva A., Avalos Angeles H., Hernandez Miguel Angel H. Steroids 64/6, ss. 379-386, 1999).Methods of obtaining androst-4-en-3,17-dione from testosterone by biotransformation using microbial enzyme systems are known (Atta-ur-Ra-hman, M. Iqbal Choudghary, Fahim Asif, Afgan Farooq, M. Yaqoob Nat. Prod. Lett. 12/4, pp. 255-261, 1998 and Cabeza Marisa S., Gutierrez Edgar B., Garcia Genoveva A., Avalos Angeles H., Hernandez Miguel Angel H. Steroids 64/6, pp. 379- 386, 1999).
W wyżej wymienionych przypadkach androst-4-en-3,17-dion otrzymywano z testosteronu, przy czym biotransformację prowadzono przy użyciu kultur drobnoustrojów Curvularia lunata i Pleurotus ostreatus oraz Penicillium chrysogenum i Penicillium crustosum.In the above-mentioned cases, androst-4-en-3,17-dione was obtained from testosterone, and the biotransformation was carried out using cultures of Curvularia lunata and Pleurotus ostreatus as well as Penicillium chrysogenum and Penicillium crustosum.
Znany jest też sposób otrzymywania androst-4-en-3,17-dionu z testosteronu na drodze chemicznej (John Fried i John A. Edwards, Organic Reactions in Steroid Chemistry volume I, s. 239, 1972).There is also a known method of obtaining androst-4-ene-3,17-dione from testosterone by chemical means (John Fried and John A. Edwards, Organic Reactions in Steroid Chemistry volume I, pp. 239, 1972).
Wynalazek dotyczy sposobu wytwarzania androst-4-en-3,17-dionu z testosteronu na drodze mikrobiologicznej.The invention relates to a process for the preparation of androst-4-ene-3,17-dione from testosterone by microbiological means.
Istota wynalazku polega na tym, że substrat, o wzorze 1, poddaje się biotransformacji, w której jako bioreagenta używa się systemu enzymatycznego drobnoustroju Epithyrium resinae.The essence of the invention lies in the fact that the substrate of formula I is biotransformed, in which the enzyme system of the microorganism Epithyrium resinae is used as a bioreactant.
Korzystnie jest gdy biotransformację prowadzi się wodną kulturą szczepu, w temperaturze 288 - 308 K, przy ciągłym mieszaniu oraz gdy do 250 - 500 cm3 kultury dodaje się 60- 160 mg substratu.When the biotransformation is preferably carried out with an aqueous culture of the strain at a temperature of 288 - 308 K while stirring and when the 250 - 500 cm 3 of the culture was added 60 to 160 mg of substrate.
W wyniku działania układu enzymatycznego kultury Epithyrium resinae zachodzi utlenienie 17β alkoholu do ketonu. Otrzymany w ten sposób produkt wydziela się z wodnej kultury mikroorganizmu przez ekstrakcję chlorkiem metylenu.As a result of the enzyme system of the Epithyrium resinae culture, the alcohol 17β is oxidized to a ketone. The product thus obtained is separated from the aqueous culture of the microorganism by extraction with methylene chloride.
Zaletą wynalazku jest otrzymanie androst-4-en-3,17-dionu, jako głównego produktu reakcji, z wydajnością 75%.The advantage of the invention is to obtain androst-4-ene-3,17-dione as the main reaction product with a yield of 75%.
Przedmiot wynalazku jest bliżej objaśniony w przykładzie wykonania.The subject of the invention is explained in more detail in an exemplary embodiment.
Przykład. Do kolby o pojemności 2 dm3 zawierającej 350 cm3 sterylnej pożywki, sporządzonej przez rozpuszczenie 30 g glukozy i 10 g peptonu w 1 dm3 wody, wprowadza się szczep Epithyrium resinae. Po ośmiu dniach wzrostu mikroorganizmu w temperaturze około 300 K i ciągłym wstrząsaniu dodaje się substrat testosteron (wzór 1). Substrat rozpuszcza się w acetonie (ok. 1 cm3) i dodaje, w ilości 120 mg, do 350 cm3 płynnej kultury drobnoustroju. Transformację prowadzi się przy ciągłym wstrząsaniu przez 5 dni.Example. To a flask containing 2 dm 3 350 cm 3 of the sterile medium prepared by dissolving 30 g of glucose and 10 g of peptone in 1 dm 3 of water is introduced strain Epithyrium resinae. After eight days of growth of the microorganism at a temperature of about 300 K and continuous shaking, the testosterone substrate (formula 1) is added. The substrate is dissolved in acetone (approx. 1 cm 3 ) and added, in an amount of 120 mg, to 350 cm 3 of the liquid culture of the microorganism. The transformation is carried out under continuous shaking for 5 days.
Następnie, uzyskany roztwór transformacyjny ekstrahuje się trzykrotnie chlorkiem metylenu, osusza siarczanem magnezu i odparowuje rozpuszczalnik na wyparce rotacyjnej. Otrzymuje się 110 mg surowego produktu, który oczyszcza się chromatograficznie, używając jako eluentu mieszaniny heksan:aceton w stosunku 2:1. Na tej drodze otrzymuje się 90 mg androst-4-en-3,17-dionu (wydajność 75%).Thereafter, the resulting transformation solution was extracted three times with methylene chloride, dried with magnesium sulfate and the solvent was evaporated on a rotary evaporator. 110 mg of crude product is obtained, which product is purified by chromatography using a 2: 1 mixture of hexane: acetone as the eluent. In this way, 90 mg of androst-4-ene-3,17-dione are obtained (75% yield).
Uzyskany produkt charakteryzuje się następującymi danymi spektralnymi:The obtained product is characterized by the following spectral data:
1H NMR (CDCla) d: 0,93 (3H, s, C-18H), 1,22 (3H, s, C-19H). 1 H NMR (CDCl) d: 0.93 (3H, s, C-18H), 1.22 (3H, s, C-19H).
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL347952A PL194401B1 (en) | 2001-06-05 | 2001-06-05 | Method of obtaining androst-4-ene 3,17-dione |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL347952A PL194401B1 (en) | 2001-06-05 | 2001-06-05 | Method of obtaining androst-4-ene 3,17-dione |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL347952A1 PL347952A1 (en) | 2001-12-03 |
| PL194401B1 true PL194401B1 (en) | 2007-05-31 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL347952A PL194401B1 (en) | 2001-06-05 | 2001-06-05 | Method of obtaining androst-4-ene 3,17-dione |
Country Status (1)
| Country | Link |
|---|---|
| PL (1) | PL194401B1 (en) |
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2001
- 2001-06-05 PL PL347952A patent/PL194401B1/en not_active IP Right Cessation
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| Publication number | Publication date |
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| PL347952A1 (en) | 2001-12-03 |
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| Date | Code | Title | Description |
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| LICE | Declarations of willingness to grant licence |
Effective date: 20070122 |
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| LAPS | Decisions on the lapse of the protection rights |
Effective date: 20040605 |