Patent GB-1320302-A (GB)
Title: 21-fluoro-16,17-dihydroxy-pregnane compounds and their derivatives
Inventor: ANNER G
IPC: A23K1/165
Filed: 1971-04-19
Abstract: 1320302 21 - Fluoro - 16,17 - dihydroxypregnanes and their derivatives CIBA-GEIGY AG 19 April 1971 [17 April 1970 (2)] 9795/71 Heading C2U Novel steroids of the formula (wherein X is H, Cl or F and R 1  and R 2  are each free, esterified or etherified OH groups or together are O-C(=Z)-O where Z is two aliphatic, aromatic or araliphatic hydrocarbon radicals which may be the same or different or is a cycloalkylidene group) and their 1-dehydro derivatives are prepared by dehydrogenation and, where necessary, insertion of X into the corresponding #<SP>4</SP> - 3 - keto - 6 - unsubstituted steroids or by insertion of R 2  into the corresponding 16-unsubstituted steroids. A # -with or without a #<SP>1</SP>-double bond may be inserted by use of a dehydrogenating quinone and a 6- halo substituent inserted into the product via a 6,7-epoxide and possibly also via a 6#-halo- 7α-ol. Alternatively the 6-halogen atom and the #<SP>6</SP>-double bond may be inserted in one step via a #<SP>3,5</SP>-3-enol ether. Also, the 6-substituent may be inserted before dehydrogenation, for example by treatment of a #<SP>3,5</SP>-3-enol ether with a derivative of HOCl, or by converting the #<SP>4</SP>-3-one to a #<SP>5</SP>-3-ketal, converting this to the 5,6 epoxide, and treating this with HF or HCl, or by converting the ketal to a 5,6-dihalo compound and dehydrohalogenating this. A 16-OH group may be introduced microbiologically, e.g. with Streptomyces roseochromogenus. Also, in an example, 3,20-dioxo-6,21-difluoro-16α-acetoxy-17α-hydroxy-#<SP>4,6</SP>-pregnadiene is prepared by treating 3,20-dioxo-6,21-difluoro-16#-chloro- 17α-acetoxy-#<SP>4,6</SP>-pregnadiene with sodium acetate in acetic acid. In the products of these processes 16- and/or 17-OH groups may be esterified or etherified or ketalized and the derivatives may be hydrolysed. 3,20 - Dioxo - 6,21 - difluoro - 16# - chloro- 17α-acetoxy-#<SP>4,6</SP>-pregnadiene is prepared by reacting 3 - ethoxy - 16α,17α - oxido - 20 - oxo - 21- fluoro-#<SP>3,5</SP>-pregnadiene (from the #<SP>4</SP>-3-one) with perchloryl fluoride to give 3,20-dioxo-6,21-difluoro - 16α,17α - oxido - #<SP>4</SP> - pregnene (a mixture of the 6α- and 6#-epimers), converting this mixture to 3-ethoxy-6,21-difluoro-16α,17α-oxido- 20-oxo-#<SP>3,5</SP>-pregnadiene, oxidizing this with MnO 2  to give 3,20-dioxo-6,21-difluoro-16α,17α- oxido-#<SP>4,6</SP>-pregnadiene (and, as a by-product, 3,6,20 - trioxo - 16α,17α - oxido - 21 - fluoro - #<SP>4</SP>- pregnene), reacting this with HCl in CHCl 3  to give 3,20 - dioxo - 6,21 - difluoro - 16# - chloro- 17α-hydroxy-#<SP>4,6</SP>-pregnadiene and acetylating this. 3,20 - Dioxo - 16α,17α - dihydroxy - 21 - fluoro- #<SP>4</SP>-pregnene-16-17-acetonide is prepared by oxidizing 3,20 - dioxo - 21 - fluoro - #<SP>4,16</SP> - pregnadiene (from the #<SP>5</SP>-3#-ol) to give 3,20-dioxo-16α, 17α - dihydroxy - 21 - fluoro - #<SP>4</SP> - pregnene and ketalizing this. Also, the corresponding 16,17- cyclopentanonide is prepared by ketalization of the diol with cyclopentanone. The novel steroids are stated to possess gestagenic, ovulation-inhibiting and anti-inflammatory action, and they may be made up into pharmaceutical compositions with suitable carriers.