Microbiological process for the production of 7-substituted 11-hydroxy steroids, 7,17-substituted 11-halogen steroids that can be produced therefrom, their process for production and use as well as pharmaceutical prepartions that contain these compounds, as well as 7-substituted estra-1,3,5(10)-trienses that can be produced therefrom

Microbiological process for the production of 7α-substituted 11α-hydroxy steroids with general formula 4,B:

• in which
• R7 is the grouping P-Q, whereby
• P represents a C1— to C4- alkylene and Q represents a C1— to C4-alkyl- or C1— to C4-fluoroalkyl, and the grouping P-Q is bonded via P to the steroid skeleton,
• R10 can be in α- or β-position and stands for H, CH3 or CF3, and
• R13 is methyl or ethyl,
• in which a 7α-substituted steroid with general formula 3,A:
• in which R7, R10 and R13 have the same meanings as previously indicated, is hydroxylated in 11α-position in a first microbiological process step with use of a first microorganism that is selected from the group that comprises Aspergillus sp., Beauveria sp., Gibberella sp., Glomerella sp., Gnomonia sp., Metarrhizium sp., Nigrospora sp., Rhizopus sp. and Verticillium sp., with the formation of a 7α-substituted 11α-hydroxy steroid with general formula C:
• in which R7, R10 and R13 have the same meanings as indicated above, and the 7α-substituted 11α-hydroxy steroid with general formula C that is produced is then oxidized in a second microbiological process step with use of a second microorganism that is selected from the group that comprises Bacillus sp., Mycobacterium sp., Nocardia sp. and Pseudomonas sp., with the formation of the 7α-substituted steroid with general formula 4,B.

Microbiological process for the production of 7α-substituted 11α-hydroxy steroids with general formula 4,B:

• in which
• R7 is the grouping P-Q, whereby
• P represents a C1— to C4-alkylene and Q represents a C1— to C4-alkyl- or C1— to C4 -fluoroalkyl, and the grouping P-Q is bonded via P to the steroid skeleton,
• R10 stands for H, CH3 or CF3, and
• R13 is methyl or ethyl,
• in which 7α-substituted steroids with general formula D:
• in which R7, R10 and R13 have the same meanings as indicated above, are hydroxylated with use of a microorganism that is selected from the group that comprises Aspergillus sp., Beauveria sp., Curvularia sp., Gibberella sp., Glomerella sp., Gnomonia sp., Haplosporella sp., Helicostylum sp., Nigrospora sp., Rhizopus sp. and Syncephalastrum sp.

7α, 17α-Substituted 11β-halogen steroids with general formulas 8, 10, and 12:

• in which
• U—V—W—X—Y-Z stands for one of ring structures C1—C2—C3—C4═C5—C10, C1—C2—C3—C4—C5═C10 or C1—C2—C3—C4—C5—C10, whereby in this case, an oxo group (═O) is bonded to W (═C3), or for ring structure C1═C2—C3═C4—C5═C6, whereby in this case radical OR3 is bonded to W (═C3),
• R3 stands for H, C1— to C4-alkyl, C1— to C4-alkanoyl or a cyclic C3— to C7-ether with the O-atom of the OR3-radical,
• R7 is the grouping P-Q, whereby
• P represents a C1— to C4-alkylene and Q represents a C1— to C4-alkyl- or C1— to C4 -fluoroalkyl, and grouping P-Q is bonded via P to the steroid skeleton,
• R10 can be in α- or β-position and stands for H, CH3 or CF3, and is present only if X—Y-Z is not C4—C5═C10,
• R11 is a halogen,
• R13 is methyl or ethyl,
• R17 stands for H, C1— to C18-alkyl, alicyclic C1— to C18-alkyl, C1— to C18-alkenyl, alicyclic C1— to C18-alkenyl, C1—to C18-alkinyl, C1— to C18-alkylaryl, C1— to C8-alkylenenitrile or for the grouping P-Q, whereby the grouping P-Q has the above-mentioned meaning,
• R17′ stands for H, C1— to C18-alkyl, alicyclic C1— to C18-alkyl, C1— to C18-alkenyl, alicyclic C1— to C18-alkenyl, C1— to C18-alkinyl or C1— to C18-alkylaryl, whereby R17′ also can be bonded via a keto group to the 17β-oxy group, and whereby R17′ also in addition can be substituted with one or more groups NR18R19 or one or more groups SOxR20, whereby x=0, 1 or 2 and R18, R19 and R20 in each case independently of one another can have the same meaning as R17,
• as well as their pharmaceutically compatible addition salts, esters and amides.

7α-Substituted 11β-haloestra-1,3,5(10)-trienes with general formula 6:

• in which
• R3 stands for H, C1— to C4-alkyl, C1— to C4-alkanoyl or a cyclic C3— to C7-ether with the O-atom of the OR3-radical,
• R7 is the grouping P-Q, whereby
• P represents a C1— to C4-alkylene and Q represents a C1— to C4-alkyl- or C1— to C4-fluoroalkyl, and grouping P-Q is bonded via P to the steroid skeleton,
• R11 is a halogen;
• R13 is methyl or ethyl,
• as well as their pharmaceutically compatible addition salts, esters and amides.