Process for the microbial transformation of steroids
AssigneeThe Upjohn Company
InventorsJohn C. Knight, Merle G. Wovcha
Life of this patent
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Abstract
Novel compounds prepared by microbial transformation using novel mutants to selectively degrade steroids with or without 17-alkyl side chains of from 2 to 10 carbon atoms, inclusive. These compounds can be used as intermediates to make useful steroids.
Claims20
A process for preparing a compound of the formula ##STR5## which comprises cultivating a mutant microorganism selected from the group consisting of Arthrobacter, Bacillus, Brevibacterium, Corynebacterium, Nocardia, Protaminobacter, Serratia, and Streptomyces, said mutant being characterized by its ability to selectively degrade steroids with or without a 17-alkyl side chain of from 2 to 10 carbon atoms, inclusive, and accumulate predominantly 3a.alpha.-H-4.alpha.-[3'-propanol]-7a.beta.-methylhexahydro-1,5-indandione hemiketal;
- 3a.alpha.-H-4.alpha.-[3'-propanal]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone hemiacetal;
- 3a.alpha.-H-4.alpha.-[3'-propionic acid]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-indanone-.delta.-lactone ;
- and 3a.alpha.-H-4a-[3'-propanol]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-i ndanone in the fermentation beer, in an aqueous nutrient medium under aerobic conditions in the presence of a steroid with or without a 17-alkyl side chain containing from 2 to 10 carbon atoms, inclusive;
- and recovering only 3a.alpha.-H-4.alpha.-[3'-propanol]-7a.beta.-methylhexahydro-1,5-indandione hemiketal from the cultivated medium containing predominantly 3a.alpha.-H-4.alpha.-[3'-propanol]-7a.beta.-methylhexahydro-1,5-indandione hemiketal;
- 3a.alpha.-H-4.alpha.-[3'-propanal]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone hemiacetal;
- 3a.alpha.-H-4.alpha.-[3'-propionic acid]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-indanone-.delta.-lactone ;
- and 3a.alpha.-H-4.alpha.-[3'-propanol]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone.
A process for preparing a compound of the formula ##STR6## which comprises cultivating a mutant microorganism selected from the group consisting of Arthrobacter, Bacillus, Brevibacterium, Corynebacterium, Nocardia, Protaminobacter, Serratia, and Streptomyces, said mutant being characterized by its ability to selectively degrade steroids with or without a 17-alkyl side chain of from 2 to 10 carbon atoms, inclusive, and accumulate predominantly 3a.alpha.-H-4.alpha.-[3'-propanol]-7a.beta.-methylhexahydro-1,5-indandione hemiketal;
- 3a.alpha.-H-4.alpha.-[3'-propanal]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone hemiacetal;
- 3a.alpha.-H-4.alpha.-[3'-propionic acid]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-indanone-.delta.-lactone ;
- and 3a.alpha.-H-4a-[3'-propanol]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-i ndanone in the fermentation beer, in an aqueous nutrient medium under aerobic conditions in the presence of a steroid with or without a 17-alkyl side chain containing from 2 to 10 carbon atoms, inclusive;
- and recovering only 3a.alpha.-H-4.alpha.-[3'-propanol]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone hemiacetal from the cultivated medium containing predominantly 3a.alpha.-H-4.alpha.-[3'-propanol]-7a.beta.-methylhexahydro- 1,5-indandione hemiketal;
- 3a.alpha.H-4.alpha.-[3'-propanal]-5.alpha.-hydroxy-7a.beta.-methylhexahydr o-1-indanone hemiacetal;
- 3a.alpha.-H-4.alpha.-[3'-propionic acid]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-indanone-.delta.-lactone ;
- and 3a.alpha.-H-4.alpha.'[3'-propanol]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone.
A process for preparing a compound of the formula ##STR7## which comprises cultivating a mutant microorganism selected from the group consisting of Arthrobacter, Bacillus, Brevibacterium, Corynebacterium, Nocardia, Protaminobacter, Serratia, and Streptomyces, said mutant being characterized by its ability to selectively degrade steroids with or without a 17-alkyl side chain of from 2 to 10 carbon atoms, inclusive, and accumulate predominantly 3a.alpha.-H-4.alpha.-[3'-propanol]-7a.beta.-methylhexahydro-1,5-indandione hemiketal;
- 3a.alpha.-H-4.alpha.-[3'-propanal]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone hemiacetal;
- 3a.alpha.-H-4.alpha.-[3'-propionic acid]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-indanone-.delta.-lactone ;
- and 3a.alpha.-H-4a-[3'-propanol]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-i ndanone in the fermentation beer, in an aqueous nutrient medium under aerobic conditions in the presence of a steroid with or without a 17-alkyl side chain containing from 2 to 10 carbon atoms, inclusive;
- and recovering only 3a.alpha.-H-4.alpha.-[3'-propionic acid]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-indanone .delta.-lactone from the cultivated medium containing predominantly 3a.alpha.-H-4.alpha.-[3'-propanol]-7a.beta.-methylhexahydro-1,5-indandione hemiketal;
- 3a.alpha.-H-4.alpha.-[3'-propanal]-5.alpha.'hydroxy-7a.beta.-methylhexahyd ro-1-indanone hemiacetal;
- 3a.alpha.-H-4.alpha.-[3'-propionic acid]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-indanone-.delta.-lactone ;
- and 3a.alpha.-H-4.alpha.-[3'-propanol]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone.
A process for preparing a compound of the formula ##STR8## which comprises cultivating a mutant microorganism selected from the group consisting of Arthrobacter, Bacillus, Brevibacterium, Corynebacterium, Nocardia, Protaminobacter, Serratia, and Streptomyces, said mutant being characterized by its ability to selectively degrade steroids with or without a 17-alkyl side chain of from 2 to 10 carbon atoms, inclusive, and accumulate predominantly 3a.alpha.-H-4.alpha.-[3'-propanol]-7a.beta.-methylhexahydro-1,5-indandione hemiketal;
- 3a.alpha.-H-4.alpha.-[3'-propanal]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone hemiacetal;
- 3a.alpha.-H-4.alpha.-[3'-propionic acid]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-indanone-.delta.-lactone ;
- and 3a.alpha.-H-4a-[3'-propanol]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-i ndanone in the fermentation beer, in an aqueous nutrient medium under aerobic conditions in the presence of a steroid with or without a 17-alkyl side chain containing from 2 to 10 carbon atoms, inclusive;
- and recovering only 3a.alpha.-H-4.alpha.-[3'-propanol]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone from the cultivated medium containing predominantly 3a.alpha.-H-4.alpha.-[3'-propanol]-7a.beta.-methylhexahydro-1,5-indandione hemiketal;
- 3a.alpha.-H-4.alpha.-[3'-propanal]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone hemiacetal;
- 3a.alpha.-H-4.alpha.-[3'-propionic acid]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-indanone-.delta.-lactone ;
- and 3a.alpha.-H-4.alpha.-[3'-propanol]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone.
A process for preparing a fermentation beer containing predominantly compounds of the following formulae ##STR9## which comprises cultivating a mutant microorganism selected from the group consisting of Arthrobacter, Bacillus, Brevibacterium, Corynebacterium, Nocardia, Protaminobacter, Serratia, and Streptomyces, said mutant being characterized by its ability to selectively degrade steroids with or without a 17-alkyl side chain of from 2 to 10 carbon atoms, inclusive, and accumulate predominantly 3a.alpha.-H-4.alpha.-[3'-propanol]-7a.beta.-methylhexahydro-1,5-indandione hemiketal;
- 3a.alpha.-H-4.alpha.-[3'-propanal]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone hemiacetal;
- 3a.alpha.-H-4.alpha.-[3'-propionic acid]-5.alpha.-hydroxy-7a.beta.-methylhexahydro-1-indanone-.delta.-lactone ;
- and 3a.alpha.-H-4.alpha.-[3'-propanol]-5.alpha.-hydroxy-7a.beta.-methylhexahyd ro-1-indanone in the fermentation beer, in an aqueous nutrient medium under aerobic conditions in the presence of a steroid with or without a 17-alkyl side chain containing from 2 to 10 carbon atoms, inclusive.
Dependencies are inferred from the claim text.