PL237135B1 - 3β,17α-Dihydroxy-5α-chloro-6,19-oxidoandrostane and method of preparation of 3β,17α-dihydroxy-5α-chloro-6,19-oxidoandrostane - Google Patents
3β,17α-Dihydroxy-5α-chloro-6,19-oxidoandrostane and method of preparation of 3β,17α-dihydroxy-5α-chloro-6,19-oxidoandrostane Download PDFInfo
- Publication number
- PL237135B1 PL237135B1 PL426028A PL42602818A PL237135B1 PL 237135 B1 PL237135 B1 PL 237135B1 PL 426028 A PL426028 A PL 426028A PL 42602818 A PL42602818 A PL 42602818A PL 237135 B1 PL237135 B1 PL 237135B1
- Authority
- PL
- Poland
- Prior art keywords
- chloro
- oxidoandrostane
- dihydroxy
- organic solvent
- strain
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 14
- 238000002360 preparation method Methods 0.000 title description 3
- 241000907556 Mucor hiemalis Species 0.000 claims abstract description 7
- 239000003960 organic solvent Substances 0.000 claims abstract description 6
- 239000000758 substrate Substances 0.000 claims abstract description 6
- 230000009466 transformation Effects 0.000 claims description 5
- 241000233866 Fungi Species 0.000 claims description 3
- 238000004587 chromatography analysis Methods 0.000 claims description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 abstract description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 abstract description 3
- 229910052799 carbon Inorganic materials 0.000 abstract description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract description 3
- 238000000605 extraction Methods 0.000 abstract description 2
- 244000005700 microbiome Species 0.000 abstract description 2
- 230000002255 enzymatic effect Effects 0.000 abstract 1
- 238000004519 manufacturing process Methods 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- -1 steroid compounds Chemical class 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 230000002254 contraceptive effect Effects 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- WZJHIKKYJOYVAN-SPCSRKJQSA-N (1R,2S,5S,6S,9S,10S)-6-acetyl-5-methylpentacyclo[10.5.2.01,13.02,10.05,9]nonadec-13-en-15-one Chemical compound C1CC(=O)C=C2C3C[C@H]4[C@@H]5CC[C@H](C(=O)C)[C@@]5(C)CC[C@@H]4[C@]21CC3 WZJHIKKYJOYVAN-SPCSRKJQSA-N 0.000 description 1
- ZESRJSPZRDMNHY-YFWFAHHUSA-N 11-deoxycorticosterone Chemical class O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 ZESRJSPZRDMNHY-YFWFAHHUSA-N 0.000 description 1
- AURFZBICLPNKBZ-YZRLXODZSA-N 3alpha-hydroxy-5beta-pregnan-20-one Chemical class C([C@H]1CC2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)C)[C@@]2(C)CC1 AURFZBICLPNKBZ-YZRLXODZSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000192125 Firmicutes Species 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
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000002395 mineralocorticoid Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000000757 progestagenic effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P33/00—Preparation of steroids
- C12P33/06—Hydroxylating
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P33/00—Preparation of steroids
- C12P33/12—Acting on D ring
- C12P33/16—Acting at 17 position
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P33/00—Preparation of steroids
- C12P33/20—Preparation of steroids containing heterocyclic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Wood Science & Technology (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Microbiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Zgłoszenie dotyczy 3β,17α-dihydroksy-5α-chloro-6,19-oksidoandrostan i sposób wytwarzania 3β,17α-dihydroksy-5α-chloro-6,19-oksidoandrostanu o wzorze 2. Zgodnie z rozwiązaniem, w wyniku działania układu enzymatycznego zawartego w komórkach szczepu Mucor hiemalis KCh W2, następuje hydroliza grupy acetylowej przy C-3 i stereselektywna redukcja grupy karbonylowej przy węglu C-17 w substracie. Uzyskany w ten sposób produkt wydziela się z wodnej kultury mikroorganizmu, znanym sposobem, przez ekstrakcję rozpuszczalnikiem organicznym niemieszającym się z wodą (chloroform).The application concerns 3β,17α-dihydroxy-5α-chloro-6,19-oxidoandrostane and a method for producing 3β,17α-dihydroxy-5α-chloro-6,19-oxidoandrostane of formula 2. According to the solution, as a result of the action of the enzymatic system contained in cells of the Mucor hiemalis KCh W2 strain, the acetyl group at C-3 is hydrolyzed and the carbonyl group at carbon C-17 in the substrate is stereoselectively reduced. The product obtained in this way is isolated from the aqueous culture of the microorganism in a known method, by extraction with an organic solvent immiscible with water (chloroform).
Description
Opis wynalazkuDescription of the invention
Przedmiotem wynalazku jest 33,17a-dihydroksy-5a-chloro-6,19-oksidoandrostan i sposób wytwarzania 33,17a-dihydroksy-5a-chloro-6,19-oksidoandrostanu.The present invention relates to 33,17a-dihydroxy-5a-chloro-6,19-oxidoandrostane and a method for the preparation of 33,17a-dihydroxy-5a-chloro-6,19-oxidoandrostane.
Metoda, według wynalazku może znaleźć zastosowanie w przemyśle farmaceutycznym jako prekursor leków antykoncepcyjnych.The method according to the invention may find application in the pharmaceutical industry as a precursor to contraceptive drugs.
Wprowadzenie mostka 6,19-oksiranowego w strukturze związków steroidowych powoduje ugięcie szkieletu pomiędzy pierścieniami A i B. (G. Burton, M. Galigniana, S. de Lavallaz, A. L. BrachetCota, E. M Sproviero, A. A. Ghini, C. P. Lantos and M. C. Damasco, Mol. Pharmacol., 1995, 47, 535543). Wykazano, że niektóre związki posiadające takie ugrupowanie mają interesujące aktywności biologiczne. Analog 21-hydroksyprogesteronu jest selektywnym antyglukokortykoidem pozbawionym mineralokortykoidowych i progestagenowych aktywności (G. P. Vicent, M. C. Monteserin, A. S. Veleiro, G. Burton, C. P. Lantos and M. D. Galigniana, Mol. Pharmacol., 1997, 52, 749-753), a analog pregnanolonu jest silnym środkiem przeciwdrgawkowym (A. S. Veleiro, R. Rosenstein, M. L. Grilli, C. Jaliffa, F. Speroni and G. Burton, Bioorg. Med. Chem. Lett., 2003, 13, 343-346; M. Joselevich, A. A. Ghini, G. Burton 6,19-Carbon-bridged steroids. Synthesis of 6,19-methanoprogesterone. Org. Biomol. Chem. 2003, 1,939-943). Istnieją również doniesienia dotyczące działania zapobiegającego migotaniu komór serca C-19 steroidów posiadających mostek 6,19-oksiranowy. Z opisu patentowego US 3,001,989 znane są właściwości przeciwbólowe i są bakteriostatyczne wobec bakterii Gram-dodatnich. Związki steroidowe posiadające mostek 6,19-oksiranowy są prekursorami posiadających właściwości antykoncepcyjne 19-norsteroidów (B. Berkoz, E. Denot, A. Bowers. Steroids CCXXX. Conversion of 63,19-oxides and lactones into 19-nor steroids. Steroids. 1, 1963, 251-270).The introduction of a 6,19-oxirane bridge in the structure of steroid compounds causes a deflection of the skeleton between the A and B rings (G. Burton, M. Galigniana, S. de Lavallaz, AL BrachetCota, E. M Sproviero, AA Ghini, CP Lantos and MC Damasco , Mol. Pharmacol., 1995, 47, 535543). Some compounds having such a moiety have been shown to have interesting biological activities. The 21-hydroxyprogesterone analog is a selective antiglucocorticoid devoid of mineralocorticoid and progestagenic activities (GP Vicent, MC Monteserin, AS Veleiro, G. Burton, CP Lantos and MD Galigniana, Mol. Pharmacol., 1997, 52, 749-753), and the pregnanolone analog is potent anticonvulsant (AS Veleiro, R. Rosenstein, ML Grilli, C. Jaliffa, F. Speroni and G. Burton, Bioorg. Med. Chem. Lett., 2003, 13, 343-346; M. Joselevich, AA Ghini, G. Burton 6,19-Carbon-bridged steroids. Synthesis of 6,19-methanoprogesterone. Org. Biomol. Chem. 2003, 1,939-943). There are also reports of C-19 steroids with a 6,19-oxirane bridge in preventing ventricular fibrillation. From US Pat. No. 3,001,989, analgesic properties are known and are bacteriostatic against gram-positive bacteria. Steroid compounds having a 6,19-oxirane bridge are the precursors of the contraceptive properties of 19-norsteroids (B. Berkoz, E. Denot, A. Bowers. Steroids CCXXX. Conversion of 63.19-oxides and lactones into 19-nor steroids. Steroids. 1, 1963, 251-270).
Szczep Mucor hiemalis KCh W2 znany jest z opisu zgłoszenia wynalazku P.420193 ujawniony jest również w publikacji (Kozłowska E., Urbaniak M., Kancelista A., Dymarska M., Kostrzewa-Susłow E.; Stępień Ł., Janeczko T., (2017) Biotransformation of dehydroepiandrosterone (DHEA) by environmental strains of filamentous fungi. RSC Advances 2017, 7, 31493-31501).The strain Mucor hiemalis KCh W2 is known from the description of the invention application P.420193 is also disclosed in the publication (Kozłowska E., Urbaniak M., Kancelista A., Dymarska M., Kostrzewa-Susłow E .; Stępień Ł., Janeczko T., (2017) Biotransformation of dehydroepiandrosterone (DHEA) by environmental strains of filamentous fungi. RSC Advances 2017, 7, 31493-31501).
W literaturze nie ma doniesień dotyczących 33,17a-dihydroksy-5a-chloro-6,19-oksidoandrostanu.There are no reports in the literature on 33,17a-dihydroxy-5a-chloro-6,19-oxidoandrostane.
Istota wynalazku polega na tym, że do podłoża odpowiedniego dla grzybów strzępkowych wprowadza się szczep Mucor hiemalis KCh W2. Po upływie co najmniej 48 godzin do hodowli wprowadza się substrat, którym jest 33-acetyloksyy-5a-chloro-6,19-oksidoandrostan-17-on o wzorze 1, rozpuszczony w rozpuszczalniku organicznym mieszającym się z wodą. Transformację prowadzi się w temperaturze od 20 do 30 stopni Celsjusza, przy ciągłym wstrząsaniu, co najmniej 24 godzin. Kolejno produkt ekstrahuje się rozpuszczalnikiem organicznym niemieszającym się z wodą i oczyszcza chromatograficznie.The essence of the invention consists in introducing the strain Mucor hiemalis KCh W2 into a medium suitable for filamentous fungi. After at least 48 hours, the substrate is introduced into the culture, which is 33-acetyloxy-5a-chloro-6,19-oxidoandrostane-17-one of the formula I, dissolved in a water-miscible organic solvent. The transformation is carried out at a temperature of 20 to 30 degrees Celsius with continuous shaking for at least 24 hours. Subsequently, the product is extracted with a water-immiscible organic solvent and purified by chromatography.
W wyniku hydrolizy grupy acetylowej przy C-3 i stereselektywnej redukcji grupy karbonylowej przy węglu C-17, otrzymuje się 33,17a-dihydroksy-5a-chloro-6,19-oksidoandrostan, a reakcję prowadzi się w wodnej kulturze szczepu Mucor hiemalis KCh W2.As a result of the hydrolysis of the acetyl group at C-3 and the stereselective reduction of the carbonyl group at the C-17 carbon, 33,17a-dihydroxy-5a-chloro-6,19-oxidoandrostane is obtained, and the reaction is carried out in an aqueous culture of the strain Mucor hiemalis KCh W2 .
Korzystnie jest, gdy stosunek masy dodawanego substratu do objętości hodowli wynosi 0,2 g : 1 L.Preferably, the ratio of the mass of the added substrate to the culture volume is 0.2 g: 1 L.
Korzystnie także jest, gdy proces prowadzi się w temperaturze 25 stopni Celsjusza.It is also preferred that the process is carried out at a temperature of 25 degrees Celsius.
Dodatkowo, korzystnie jest, gdy transformację prowadzi się przez 3 dni.Additionally, it is preferred that the transformation is carried out for 3 days.
Postępując zgodnie z wynalazkiem, w wyniku działania układu enzymatycznego zawartego w komórkach szczepu Mucor hiemalis KCh W2, następuje hydroliza grupy acetylowej przy C-3 i stereselektywna redukcja grupy karbonylowej przy węglu C-17 w substracie. Uzyskany w ten sposób produkt wydziela się z wodnej kultury mikroorganizmu, znanym sposobem, przez ekstrakcję rozpuszczalnikiem organicznym niemieszającym się z wodą (chloroform). Zasadniczą zaletą wynalazku jest otrzymanie 33,17a-dihydroksy-5a-chloro-6,19-oksidoandrostanu, z wydajnością izolowaną na poziomie 20% (konwersja według GC = 54%), w temperaturze pokojowej i przy pH naturalnym dla szczepu.Proceeding according to the invention, as a result of the enzyme system contained in the cells of the Mucor hiemalis KCh W2 strain, hydrolysis of the acetyl group at C-3 takes place and the stereselective reduction of the carbonyl group at the C-17 carbon in the substrate. The product obtained in this way is separated from the aqueous culture of the microorganism by a known method by extraction with a water-immiscible organic solvent (chloroform). The main advantage of the invention is the preparation of 33,17a-dihydroxy-5a-chloro-6,19-oxidoandrostane with an isolated yield of 20% (GC conversion = 54%), at room temperature and pH natural for the strain.
Wynalazek jest bliżej objaśniony na przykładzie wykonania.The invention is explained in more detail using an exemplary embodiment.
P r z y k ł a d. Do kolby Erlenmajera o pojemności 2000 cm3, w której znajduje się 500 cm3 sterylnej pożywki zawierającej 5 g aminobaku i 15 g glukozy, wprowadza się szczep Mucor hiemalis KCh W2. Po 72 godzinach jego wzrostu dodaje się 100 mg 33-acetyloksy-5a-chloro-6,19-oksidoandrostan-17-onu o wzorze 1, rozpuszczonego w 1 cm3 DMSO. Transformację prowadzi się w 25 stopniach Celsjusza przy ciągłym wstrząsaniu przez 3 dni. Następnie mieszaninę poreakcyjną ekstrahuje się trzykrotnie chloroformem, osusza bezwodnym siarczanem magnezu i odparowuje rozpuszczalnik. Otrzymany ekstrakt oczyszcza się chromatograficznie, używając jako eluentu mieszaniny heksan i aceton 2:1.Example d. To the Erlenmeyer flask with a capacity of 2,000 cm 3, which is 500 cm 3 of a sterile medium containing 5 g aminobaku and 15 g of glucose, introduced strain of Mucor hiemalis SDS W2. After 72 hours the growth was added 100 mg of 33-acetyloxy-5-chloro-6,19-oksidoandrostan-17-one of formula 1, dissolved in 1 cm 3 of DMSO. The transformation is carried out at 25 degrees Celsius with continuous shaking for 3 days. The reaction mixture was then extracted three times with chloroform, dried with anhydrous magnesium sulfate, and the solvent was evaporated. The extract obtained is purified by chromatography using a 2: 1 mixture of hexane and acetone as the eluent.
PL 237 135 B1PL 237 135 B1
Na tej drodze otrzymuje się 20 mg 33,17a-dihydroksy-5a-chloro-6,19-oksidoandrostanu (konwersja według GC = 54%).In this way, 20 mg of 33.17a-dihydroxy-5a-chloro-6,19-oxidoandrostane are obtained (GC conversion = 54%).
Uzyskany produkt charakteryzuje się następującymi danymi spektralnymi:The obtained product is characterized by the following spectral data:
1H NMR (600 MHz) (ppm) (CDCI3) δ: 0.70 (s, 3H, 18-H); 1.20 (dt, 1H, J = 12.9, 3.9 Hz, 11-Hp); 1.28-1.37 (m, 1H, 7-Ha); 1.44-1.67 (m, 6H, 1-Ha, 2-Ha, 11-Ha, 14-H, 15-Κβ, 16-Ha); 1.58-1.73 (m, 6H, 1-Κβ, 7-Hβ, 8-H, 9-H, 12-Ha, 15-Ha); 1.84-1.98 (m, 3H, 2-Hβ, 12-Hβ, 16-Hβ); 2.04 (dd, 1H, J = 13.6, 1.13 Hz, 4-Ha); 2.19 (ddd, 1H, J = 13.5, 4.3, 2.4 Hz, 4Ήβ); 3.75 (d, 1H, J = 5.9 Hz, 17-Hβ); 3.81 (d, 1H, J = 8.5 Hz, one of 19-H); 3.91 (d, 1H, J = 8.3 Hz, one of 19-H); 4.00 (d, 1H, J = 4.4 Hz, 6-Ha); 4.07 (tt, 1H, J = 1.14, 4.2 Hz, 3-Ha). 1 H NMR (600 MHz) (ppm) (CDCl 3) δ: 0.70 (s, 3H, 18-H); 1.20 (dt, 1H, J = 12.9, 3.9Hz, 11-Hp); 1.28-1.37 (m, 1H, 7-Ha); 1.44-1.67 (m, 6H, 1-Ha, 2-Ha, 11-Ha, 14-H, 15-Κβ, 16-Ha); 1.58-1.73 (m, 6H, 1-Κβ, 7-Hβ, 8-H, 9-H, 12-Ha, 15-Ha); 1.84-1.98 (m, 3H, 2-Hβ, 12-Hβ, 16-Hβ); 2.04 (dd, 1H, J = 13.6, 1.13 Hz, 4-Ha); 2.19 (ddd, 1H, J = 13.5, 4.3, 2.4 Hz, 4Ήβ); 3.75 (d, 1H, J = 5.9Hz, 17-Hβ); 3.81 (d, 1H, J = 8.5Hz, one of 19-H); 3.91 (d, 1H, J = 8.3Hz, one of 19-H); 4.00 (d, 1H, J = 4.4 Hz, 6-Ha); 4.07 (mp, 1H, J = 1.14, 4.2 Hz, 3-Ha).
13C NMR (151 MHz) (ppm) (CDCI3) δ: 23,91 (C-1); 30,89 (C-2); 66,53 (C-3); 44,14 (C-4); 76,31 (C-5); 82,36 (C-6); 31,59 (C-7); 33,60 (C-8); 46,92 (C-9); 45,82 (C-10); 22,15 (C-11); 32,23 (C-12); 46,02 (C-13); 46,93 (C-14); 23,71 (C-15); 32,69 (C-16); 79,71 (C-17); 17,55 (C-18); 68,70 (C-19). 13 C NMR (151 MHz) (ppm) (CDCl 3) δ: 23.91 (C-1); 30.89 (C-2); 66.53 (C-3); 44.14 (C-4); 76.31 (C-5); 82.36 (C-6); 31.59 (C-7); 33.60 (C-8); 46.92 (C-9); 45.82 (C-10); 22.15 (C-11); 32.23 (C-12); 46.02 (C-13); 46.93 (C-14); 23.71 (C-15); 32.69 (C-16); 79.71 (C-17); 17.55 (C-18); 68.70 (C-19).
Claims (5)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL426028A PL237135B1 (en) | 2018-06-22 | 2018-06-22 | 3β,17α-Dihydroxy-5α-chloro-6,19-oxidoandrostane and method of preparation of 3β,17α-dihydroxy-5α-chloro-6,19-oxidoandrostane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PL426028A PL237135B1 (en) | 2018-06-22 | 2018-06-22 | 3β,17α-Dihydroxy-5α-chloro-6,19-oxidoandrostane and method of preparation of 3β,17α-dihydroxy-5α-chloro-6,19-oxidoandrostane |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL426028A1 PL426028A1 (en) | 2020-01-02 |
| PL237135B1 true PL237135B1 (en) | 2021-03-22 |
Family
ID=69160774
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL426028A PL237135B1 (en) | 2018-06-22 | 2018-06-22 | 3β,17α-Dihydroxy-5α-chloro-6,19-oxidoandrostane and method of preparation of 3β,17α-dihydroxy-5α-chloro-6,19-oxidoandrostane |
Country Status (1)
| Country | Link |
|---|---|
| PL (1) | PL237135B1 (en) |
-
2018
- 2018-06-22 PL PL426028A patent/PL237135B1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL426028A1 (en) | 2020-01-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Wang et al. | Biocatalytic allylic hydroxylation of unsaturated triterpenes and steroids by Bacillus megaterium CGMCC 1.1741 | |
| Choudhary et al. | Biotransformation of (20S)-20-hydroxymethylpregna-1, 4-dien-3-one by four filamentous fungi | |
| HUT70524A (en) | Novel makrolides and their use | |
| Zhu et al. | New approaches to the structural modification of olean-type pentacylic triterpenes via microbial oxidation and glycosylation | |
| Hsu et al. | Biotransformation of gallic acid by Beauveria sulfurescens ATCC 7159 | |
| PL237134B1 (en) | 3β,11α-Dihydroxy-5α-chloro-6,19-oxidoandrostan-17-one and method of preparation of 3β,11α-dihydroxy-5α-chloro-6,19-oxidoandrostan-17-one | |
| PL239563B1 (en) | 3β-Hydroxy-5α-chloro-17a-oxa-D-homo-6,19-oxidoandrostan-17-one and method of preparation of 3β-hydroxy-5α-chloro-17a-oxa-D-homo-6,19-oxidoandrostane-17-one | |
| PL237710B1 (en) | 3β-Hydroxy-5α-chloro-6,19-oxidoandrostan-17-one and method of preparation of 3β-hydroxy-5α-chloro-6,19-oxidoandrostan-17-one | |
| PL237709B1 (en) | 3β-Hydroxy-5α-chloro-6,19-oxidoandrostan-17-one and method of preparation of 3β-hydroxy-5α-chloro-6,19-oxidoandrostan-17-one | |
| PL237711B1 (en) | 3β-Hydroxy-5α-chloro-6,19-oxidoandrostan-17-one and method of preparation of 3β-hydroxy-5α-chloro-6,19-oxidoandrostan-17-one | |
| CN104352505B (en) | Applications of protopanaxatriol and derivatives thereof in preparation of medicines for treating hepatic disease | |
| PL239564B1 (en) | 3β-Hydroxy-5α-chloro-17a-oxa-D-homo-6,19-oxidoandrostan-17-one and method of preparation of 3β-hydroxy-5α-chloro-17a-oxa-D-homo-6,19-oxidoandrostane-17-one | |
| Baydoun et al. | Microbial-catalysed derivatization of anti-cancer drug exemestane and cytotoxicity of resulting metabolites against human breast adenocarcinoma cell line (MCF-7) in vitro | |
| PL228764B1 (en) | Method for producing 6β-hydroxyandrost-4-en-3,11,17-trione | |
| PL236834B1 (en) | 3β,11α-Dihydroxy-5α-chloro-17a-oxa-D-homo-6,19-oxidoandrostan-17-one and method of preparation of 3β,11α-dihydroxy-5α-chloro-17a-oxa-D-homo-6,19 oksidoandrostan-17-one | |
| PL238288B1 (en) | 6β,11α-dihydroxy-16α,17α-epoxyprogesterone and method for producing 6β,11α-dihydroksy-16α,17α-epoxyprogesterone | |
| JP2018196327A (en) | Sterol production method | |
| PL235020B1 (en) | Method for producing 3?,7?,17?-trihydroxyandrost-5-ene | |
| PL237127B1 (en) | Method for producing 6β,11α-dihydroxyprogesterone | |
| PL241536B1 (en) | Process for the preparation of 9α-hydroxyoxandrolone | |
| PL246071B1 (en) | Method of producing 11α-hydroxy-19-nortestosterone | |
| PL246161B1 (en) | Method of producing 19-nortestololactone | |
| PL237128B1 (en) | Method for producing 6β,11α-dihydroxyprogesterone | |
| PL235018B1 (en) | Method for producing 17a-oxa-D-homo-androst-4-en-17-one | |
| PL235022B1 (en) | Method for producing 6β-hydroxyandrost-4-en-3,17-dione |