US 5,225,335 AGranted

1,2-dehydrogenation of steroidal 21-esters with Arthrobacter simplex or Bacterium cyclooxydans

AssigneeThe Upjohn Company

InventorsLeo A. Kominek, Holly J. Wolf, Paula S. Steiert

Life of this patent

Estimating the term…

Abstract

The present invention involves processes for 1,2-dehydrogenation of .DELTA..sup.4 -3-keto C.sub.21 -hemiester steroids of formula (I) ##STR1## with Arthrobacter simplex or Bacterium cyclooxydans to produce the corresponding .DELTA..sup.1,4 -3-keto C.sub.21 hemiester of formula (II) ##STR2## or free alcohol thereof with improved yields. The advantage is that the processes utilize higher substrate concentrations and give shorter reaction times than previously were known.

Claims21

Dependent claims

A process for the production of a .DELTA..sup.1,4 -3-keto 21-hemiester steroid of formula (II)

where
(B-I) R.sub.6 is .dbd.CH.sub.2 or .alpha.-R.sub.6-1 :.beta.-H where R.sub.6-1 is --H, --F or --CH.sub.3, R.sub.7 is .alpha.-H:.beta.-H;
(B-II) R.sub.6 is R.sub.6-3 :R.sub.6-4 and R.sub.7 is R.sub.7-3 :R.sub.7 -4 where one of R.sub.6-3 and R.sub.6-4 taken together with one of R.sub.7-3 and R.sub.7-4 form a second bond between C.sub.6 and C.sub.7, the other of R.sub.6-3 and R.sub.6-4 is --CH.sub.3 and the other of R.sub.7-3 and R.sub.7-4 is --H;
(C-I) R.sub.11 is .alpha.-R.sub.11-1 :.beta.-R.sub.11-2 where one of R.sub.11-1 and R.sub.11-2 is taken together with R.sub.9 to form a second bond between C.sub.9 and C.sub.11, and the other of R.sub.11-1 and R.sub.11-2 is --H;
(C-II) R.sub.9 is --H, --F, --Cl or --Br and R.sub.11 is .dbd.O or .alpha.-R.sub.11-3 :.beta.-R.sub.11-4 where one of R.sub.11-3 and R.sub.11-4 is --H and the other of R.sub.11-3 and R.sub.11-4 is --H or --OH;
(CIII) R.sub.11 is .alpha.-H:.beta.-O--, where .beta.-O-- is taken together with R.sub.9 to form an epoxide between C.sub.9 and C.sub.11 in the .beta.- configuration;
(D-I) R.sub.16 is R.sub.16-1 :R.sub.16-2 and R.sub.17 is R.sub.17-1 :R.sub.17-2, where one of R.sub.16-1 and R.sub.16-2 is --H and the other taken together with one of R.sub.17-1 or R.sub.17-2 forms a second bond between C.sub.16 and C.sub.17 and the other of R.sub.17-1 and R.sub.17-2 is --CO--CH.sub.2 --O--R.sub.21 where R.sub.21 is --H, --CO--(X.sub.1)--COOR.sub.21-1, where X.sub.1 is --CH.dbd.CH-- and --(CH.sub.2).sub.n1 -- where n.sub.1 is 1-8 and where R.sub.21-1 is --H or a cation;
(D-II) R.sub.16 is .alpha.-H:.beta.-H, and where R.sub.17 is .dbd.CH--CO.sub.2 --O--R.sub.21 where R.sub.21 is as defined above;
(D-III) R.sub.16 is .dbd.CH.sub.2 or .alpha.-R.sub.16-5 :.beta.-R.sub.16-6 where R.sub.16-5 is --H, --OH or --CH.sub.3, R.sub.16-6 is --H or --CH.sub.3 with the proviso that one of R.sub.16-5 or R.sub.16-6 is --H, and where R.sub.17 is .alpha.-R.sub.17-5 :.beta.-CO--CH.sub.2 --O--R.sub.21 where R.sub.17-5 is --H or --OH, where R.sub.21 is as defined above, which comprises contacting a .DELTA..sup.4 -3-keto 21-hemiester steroid of formula (I) ##STR4## where (D-I) R.sub.16 is R.sub.16-1 :R.sub.16-2 and R.sub.17 is R.sub.17-1 :R.sub.17-2, where one of R.sub.16-1 and R.sub.16-2 is --H and the other taken together with one of R.sub.17-1 or R.sub.17-2 forms a second bond between C.sub.16 and C.sub.17 and the other of R.sub.17-1 and R.sub.17-2 is --CO--CH.sub.2 --O--CO--(X.sub.1)--COOR.sub.21-1, where X.sub.1 and R.sub.21-1 are as defined above;
(D-II) R.sub.16 is .alpha.-H:.beta.-H, and where R.sub.17 is .dbd.CH--CH.sub.2 --O--CO--(X.sub.1)--COOR.sub.21-1 where X.sub.1 and R.sub.21-1 are as defined above;
(D-III) R.sub.16 is .dbd.CH.sub.2 or .alpha.-R.sub.16-5 :R.sub.16-6 where R.sub.16-5 is --H, --OH or --CH.sub.3, R.sub.16-6 is --H or --CH.sub.3 with the proviso that one of R.sub.16-5 or R.sub.16-6 is --H, and where R.sub.17 is .alpha.-R.sub.17-5 :.beta.-CO--CH.sub.2 --O--CO--(X.sub.1)--COOR.sub.21-1 where R.sub.17-5 is --H or --OH and where X.sub.1 and R.sub.21-1 are as defined above, and where R.sub.6, R.sub.0 and R.sub.11 are as defined above, with the Arthrobacter simplex, Bacterium cyclooxydans, or the steroid .DELTA..sup.2 -dehydrogenase therefrom.

8 more elements

Dependencies are inferred from the claim text.

patentgrep

Loading patent…

Abstract

A process for the production of a .DELTA..sup.1,4 -3-keto 21-hemiester steroid of formula (II)

where
(B-I) R.sub.6 is .dbd.CH.sub.2 or .alpha.-R.sub.6-1 :.beta.-H where R.sub.6-1 is --H, --F or --CH.sub.3, R.sub.7 is .alpha.-H:.beta.-H;
(B-II) R.sub.6 is R.sub.6-3 :R.sub.6-4 and R.sub.7 is R.sub.7-3 :R.sub.7 -4 where one of R.sub.6-3 and R.sub.6-4 taken together with one of R.sub.7-3 and R.sub.7-4 form a second bond between C.sub.6 and C.sub.7, the other of R.sub.6-3 and R.sub.6-4 is --CH.sub.3 and the other of R.sub.7-3 and R.sub.7-4 is --H;
(C-I) R.sub.11 is .alpha.-R.sub.11-1 :.beta.-R.sub.11-2 where one of R.sub.11-1 and R.sub.11-2 is taken together with R.sub.9 to form a second bond between C.sub.9 and C.sub.11, and the other of R.sub.11-1 and R.sub.11-2 is --H;
(C-II) R.sub.9 is --H, --F, --Cl or --Br and R.sub.11 is .dbd.O or .alpha.-R.sub.11-3 :.beta.-R.sub.11-4 where one of R.sub.11-3 and R.sub.11-4 is --H and the other of R.sub.11-3 and R.sub.11-4 is --H or --OH;
(CIII) R.sub.11 is .alpha.-H:.beta.-O--, where .beta.-O-- is taken together with R.sub.9 to form an epoxide between C.sub.9 and C.sub.11 in the .beta.- configuration;
(D-I) R.sub.16 is R.sub.16-1 :R.sub.16-2 and R.sub.17 is R.sub.17-1 :R.sub.17-2, where one of R.sub.16-1 and R.sub.16-2 is --H and the other taken together with one of R.sub.17-1 or R.sub.17-2 forms a second bond between C.sub.16 and C.sub.17 and the other of R.sub.17-1 and R.sub.17-2 is --CO--CH.sub.2 --O--R.sub.21 where R.sub.21 is --H, --CO--(X.sub.1)--COOR.sub.21-1, where X.sub.1 is --CH.dbd.CH-- and --(CH.sub.2).sub.n1 -- where n.sub.1 is 1-8 and where R.sub.21-1 is --H or a cation;
(D-II) R.sub.16 is .alpha.-H:.beta.-H, and where R.sub.17 is .dbd.CH--CO.sub.2 --O--R.sub.21 where R.sub.21 is as defined above;
(D-III) R.sub.16 is .dbd.CH.sub.2 or .alpha.-R.sub.16-5 :.beta.-R.sub.16-6 where R.sub.16-5 is --H, --OH or --CH.sub.3, R.sub.16-6 is --H or --CH.sub.3 with the proviso that one of R.sub.16-5 or R.sub.16-6 is --H, and where R.sub.17 is .alpha.-R.sub.17-5 :.beta.-CO--CH.sub.2 --O--R.sub.21 where R.sub.17-5 is --H or --OH, where R.sub.21 is as defined above, which comprises contacting a .DELTA..sup.4 -3-keto 21-hemiester steroid of formula (I) ##STR4## where (D-I) R.sub.16 is R.sub.16-1 :R.sub.16-2 and R.sub.17 is R.sub.17-1 :R.sub.17-2, where one of R.sub.16-1 and R.sub.16-2 is --H and the other taken together with one of R.sub.17-1 or R.sub.17-2 forms a second bond between C.sub.16 and C.sub.17 and the other of R.sub.17-1 and R.sub.17-2 is --CO--CH.sub.2 --O--CO--(X.sub.1)--COOR.sub.21-1, where X.sub.1 and R.sub.21-1 are as defined above;
(D-II) R.sub.16 is .alpha.-H:.beta.-H, and where R.sub.17 is .dbd.CH--CH.sub.2 --O--CO--(X.sub.1)--COOR.sub.21-1 where X.sub.1 and R.sub.21-1 are as defined above;
(D-III) R.sub.16 is .dbd.CH.sub.2 or .alpha.-R.sub.16-5 :R.sub.16-6 where R.sub.16-5 is --H, --OH or --CH.sub.3, R.sub.16-6 is --H or --CH.sub.3 with the proviso that one of R.sub.16-5 or R.sub.16-6 is --H, and where R.sub.17 is .alpha.-R.sub.17-5 :.beta.-CO--CH.sub.2 --O--CO--(X.sub.1)--COOR.sub.21-1 where R.sub.17-5 is --H or --OH and where X.sub.1 and R.sub.21-1 are as defined above, and where R.sub.6, R.sub.0 and R.sub.11 are as defined above, with the Arthrobacter simplex, Bacterium cyclooxydans, or the steroid .DELTA..sup.2 -dehydrogenase therefrom.

8 more elements