Patent GB-1430904-A (GB)
Title: D-homopregnenes
IPC: C07J63/00
Filed: 1974-09-25
Abstract: 1430904 D-Homosteroids F HOFFMANNLA ROCHE & CO AG 25 Sept 1974 [26 Sept 1973] 41705/74 Heading C2U The invention comprises compounds of formula wherein R<SP>1</SP>=R<SP>2</SP>=H or R<SP>1</SP>+R<SP>2</SP>=1α,2α-methylene or a C-C bond; R<SP>4</SP> is H or Cl; R<SP>6</SP> is H, F, Cl, Br, Me; R<SP>17</SP> is H, Me, CH 2 , alkoxy, acyloxy: R<SP>17a</SP> is Me or acyloxy; or R<SP>17</SP> and R<SP>17a</SP> together represent where each R is H, C 1-4  alkyl or phenyl, one R alternatively being C 1-4  alkoxy; and the broken line at the 6,7-position is an optional C-C bond. Compounds I are prepared (i) from the corresponding #<SP>5</SP>-3#-ols by oxidation to give a #<SP>4</SP>,#<SP>4,6</SP> or #<SP>1,4,6</SP>-3-oxo grouping; (ii) from the corresponding 17aα-ols (which may also contain 17-OH) by acylation; (iii) from the corresponding 17α,17aα-diols by acetalization, ketalization or orthoesterification; and (iv) from the corresponding 5α-Cl, F, Br, or OH compounds by dehydrohalogenation or dehydration to introduce #<SP>4</SP>. Compounds I are interconvertible by (i) chemical or microbial 1,2- and/or 6,7-dehydrogenation; (ii) 6-halogenation or methylation, directly or via various 3-enol ether/ester, 6,7- epoxy, 6-trihalomethyl, 6-formyl and 3-enamine intermediates (vide infra for those exemplified); (iii) 6#-#6α isomerization; (iv) 4-chlorination; (v) 1,2-methylenation. 3# - Hydroxy - D - homopregna - 5,17 - dien- 20 - one (XX) -# 3# - hydroxy - 17α,17aα- epoxy - D - homopregn - 5 - en - 20 - one -# 3# - acetoxy - 17α,17aα - epoxy - D - homopregn- 5 - en - 20 - one -# 3# - acetoxy - 17# - bromo- 17aα - hydroxy - D - homopregn - 5 - en - 20- one-# 3# - acetoxy - 17aα - hydroxy - D - homopregn - 5 - en - 20 - one-# 3#,17aα - diacetoxy- D - homopregn - 5 - en - 20 - one -# 3# - hydroxy - 17aα - acetoxy - D - homopregn - 5 - en- 20 - one -# 3# - hydroxy - 5α - bromo - 6#- fluoro - 17aα - acetoxy - D - homopregnan - 20- one-# 5α - bromo - 6# - fluoro - 17aα - acetoxy- D - homopregnane - 3,20 - dione (Exx. 1 and 20). XX-# 3# - hydroxy - 17aα - methyl - D- homopregn - 5 - en - 20 - one -# 3# - hydroxy- 17aα - methyl - 20,20 - ethylenedioxy - D - homopregn - 5 - ene # 3# - hydroxy - 5α,6α - epoxy- 17aα - methyl - 20,20 - ethylenedioxy - D- homopregnane # 3#,5α - dihydroxy - 6#,17aα- dimethyl - 20,20 - ethylenedioxy - D - homopregnane -# 5α - hydroxy - 6#,17aα - dimethyl- 20,20 - ethylenedioxy - D - homopregnan - 3- one (Ex. 22). 17aα - Acetoxy. - D - homopregn - 4 - ene - 3,20- dione (XXI) # 3 - (1 - pyrrolidinyl) - 17aα- acetoxy - D - homopregna - 3,5 - dien - 20 - one # 6# - hydroxy - 17aα - acetoxy - D - homopregn - 4 - ene - 3,20 - dione (by-product) + 6#- hydroxymethyl - 17aα - acetoxy - D - homopregn - 4 - ene - 3,20 - dione # 6 - methylene - 17aα- acetoxy - D - homopregn - 4 - ene - 3,20 - dione (Ex. 10). XXI # 3 - methoxy - 17aα - acetoxy - D- homopregna - 3,5 - dien - 20 - one # 6# - tribromomethyl - 17aα - acetoxy - D - homopregn - 4 - ene - 3,20 - dione # 6 - dibromomethylene - 17aα - acetoxy - D - homopregn - 4- ene-3,20-dione (Ex. 11).  XXI # 17aα - hydroxy - D - homopregn - 4- ene - 3,20 - dione # 3,17aα - diacetoxy - D- homopregna-3,5-dien-20-one (Ex. 14). D - Homopregna - 4,17 - diene - 3,20 - dione # cyclic osmate # 17α, 17aα - dihydroxy- D - homopregn - 4 - ene - 3,20 - dione (Ex. 12). 17aα - Acetoxy - D - homopregna - 4,6 - diene- 3,20 - dione # 17aα - -acetoxy - 6α,7α - epoxy- D - homopregn - 4 - ene - 3,20 - dione # 6#- fluoro - 7α - hydroxy - 17aα - acetoxy - D- homopregn - 4 - ene - 3,20 - dione # 6# fluoro - 7α - mesyloxy - 17aα - acetoxy - D - homopregn-4-ene-3,20-dione (Ex. 5). 1α,2α - Methylene - 17aα - acetoxy - D - homopregna - 4,6 - diene - 3,20 - dione # 1α,2α- methylene - 6α,7α - epxoy - 17aα - acetoxy - D- homopregn - 4 - ene - 3,20 - dione # 1α,2α- methylene - 6# - chloro - 7α - hydroxy - 17aα- acetoxy - D - homopregn - 4 - ene - 3,20 - dione # 1α,2α - methylene - 6# - chloro - 7α - mesyloxy- 17aα - acetoxy - D - homopregn - 4 - ene - 3,20- dione (Ex. 9). Other specific compounds mentioned in the description as intermediates are: 3,17aα-dihydroxy - D - homopregn - 5 - en - 20 - one 3,17aα- dihydroxy - 6 - methyl - D - homopregn - 5 - en- 20 - one; 3,17aα - diacetoxy - 5α - bromo - 6#- hydroxy - 20,20 - ethylenedioxy - D - homopregnane; 3,17aα - diacetoxy - 20,20 - ethylenedioxy- 5# - D - homo - pregnan - 6 - one; 3#,5α,17aα- trihydroxy - 6,17α - dimethylpregnan - 20 - one; and 17aα - hydroxy - 6,17α - dimethylpregn - 4- ene-3,20-dione. Compounds I are said to exert hormonal (e.g. progestational) activity on the endocrine system, and may be made up with carriers into pharmaceutical compositions for oral, parenteral, rectal and topical administration.