Microbiological process for the production of 7-substituted 11-hydroxy steroids, 7,17-substituted 11-Halogen steroids and uses thereof
AssigneeBayer Schering Pharma Aktiengesellschaft
InventorsLudwig Zorn, Rolf Bohlmann, Norbert Gallus, Hermann Kuenzer, Hans-Peter Muhn, Reinhard Nubbemeyer
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Abstract
A novel method of synthesis for the manufacture of upstream products for the production of compounds with general formulas 8, 10, and 12 is described. In this synthesis, compounds with general formula 4,B are produced in a microbiological reaction. The meanings of R7, R10, R11, R13, R17 and R17′ as well as of the grouping U—V—W—X—Y—Z are indicated in the claims
Claims10
A microbiological process for the production of a 7α-substituted 11α-hydroxy steroids of formula 4,B
- wherein
- R7 is P—Q, wherein P is a C1- to C4-alkylene, and Q is hydrogen, C1- to C4-alkyl- or C1- to C4-fluoroalkyl, and wherein P—Q is bonded via P to the steroid skeleton,
- R10 is either in α- or β-position and is H, CH3 or CF3, and
- R13 is methyl or ethyl,
- comprising hydroxylating and oxidizing of a 7α-substituted steroid of formula 3,A,
- wherein R7, R10 and R13 are as indicated above, with use of a microorganism which is Aspergillus sp., Beauveria sp., Glomerella sp., Gnomonia sp., Haplosporella sp. or Rhizopus sp.
A microbiolociical process for the production of 7α-substituted 11 α-hydroxy steroid of formula 4,B
- wherein
- R7 is P—Q, wherein P is a C1- to C4-alkylene and Q is hydrogen, a C1- to C4-alkyl- or C1- to C4-fluoroalkyl, and wherein P—Q is bonded via P to the steroid skeleton,
- R10 is either in α- or β-position and is H, CH3 or CF3, and R13 is methyl or ethyl,
- comprising hydroxylating of a 7α-substituted steroid of formula 3,A in 11α-position,
- wherein R7, R10 and R13 are as previously indicated, using a first microorganism which is Aspergillus sp., Beauveria sp., Gibberella sp., Glomerella sp., Gnomonia sp., Metarrhizium sp., Nigrospora sp., Rhizopus sp. or Verticillium sp., to form a 7α-substituted 11α-hydroxy steroid of formula C:
- wherein R7, R10 and R13 are as indicated above, and oxidizing the 7α-substituted 11α-hydroxy steroid product of formula C with use of a second microorganism which is Bacillus sp., Mycobacterium sp., Nocardia sp. or Pseudomonas sp.
A microbiological process for the production of a 7α-substituted 11α-hydroxy steroids of formula 4,B
- wherein
- R7 is P—Q, wherein P is a C1- to C4-alkylene, and Q is hydrogen, C1- to C4-alkyl- or C1- to C4-fluoroalkyl, and wherein P—Q is bonded via P to the steroid skeleton,
- R10 is either in α- or β-position and is H, CH3 or CF3, and
- R13 is methyl or ethyl,
- comprising hydroxylating 7α-substituted steroids of formula D:
- wherein R7, R10 and R13 are as indicated above, using a microorganism which is Beauveria sp., Curvularia sp., Gibberella sp., Glomerella sp., Gnomonia sp., Haplosporella sp., Helicostylum sp., Nigrospora sp., or Syncephalastrum sp.
Dependencies are inferred from the claim text.