GB1525063A - D-homosteroids - Google Patents

Abstract

1525063 D-homo steroids F HOFFMAN-LA ROCHE & CO AG 9 April 1976 [9 April 1975] 14623/76 Heading C2U The invention comprises #<SP>4</SP> and #<SP>4,6</SP> 19-nor- D-homosteroids of formula (wherein R<SP>17a</SP> is hydroxy, acyloxy, C 1-7 alkyl or C 1-7 alkoxy; and R<SP>21</SP> is H, F or Cl); and their preparation (a) from the corresponding 3#- hydroxy-#<SP>4</SP>, #<SP>5</SP> or #<SP>5(10)</SP> compounds by oxidation (to give 3-oxo-#<SP>4</SP> or #<SP>4,6</SP>); (b) from the corresponding compounds in which the 3-oxo group is functionally converted (e.g. enamines, enol ethers and thioethers, ketals, thioketals) by hydrolysis; (c) from the corresponding #<SP>17a(20)</SP>- enes by oxidation to give a 17a-hydroxy-20-oxo grouping (conventional one- and two-stage procedures are described); (d) from the corresponding 21-ols by 21-halogenation (direct or via 21-sulphonates); (e) from the corresponding 10-formyl compounds by deformylation, e.g. with alcoholic NaOH or KOH; (f) from the corresponding saturated 5-hydroxy or 5-halo compounds by 4,5-dehydration or dehydrohalogenation, e.g. with an acid or base; (g) from the corresponding #<SP>17(17a)</SP>-enes by reductive alkylation (to give R<SP>17a</SP>=alkyl), e.g. with alkyl iodide/Li/NH 3 /THF, and with intermediate protection of the 3-oxo group; (h) from the corresponding 17aα-H compounds by 17aα-hydroxylation, e.g. with O 2 /HOBu<SP>t</SP>/Bu<SP>t</SP>OH/P(OMe) 3 / DMF, and with intermediate protection of the 3-oxo group. Compounds I are interconvertible by (i) 6,7-dehydrogenation, and (ii) acylation or alkylation of 17aα-OH. 3# - Hydroxy - D - homopregna - 5,17 - dien - 20 - one # 3# - acetoxy - 17α,17a - epoxy - D - homopregn - 5 - en - 20 - one # 3# - acetoxy - 17# - bromo - 17a - hydroxy - D - homopregn - 5 - en - 20 - one # 3# - acetoxy - 17a - hydroxy - D -homopregn - 5 - en - 20 - one # 3# - acetoxy - 17a - alkanoyloxy - D - homopregn - 5 - en - 20 - one (where "alkanoyloxy" is. acetoxy or hexanoyloxy) # 5 - bromo - 3# - acetoxy - 17a - alkanoyloxy - 6# - hydroxy - D - homo - 5α - pregnan - 20 - one # 5 - bromo - 3# - acetoxy - 17a - alkanoyloxy - 6#,19 - epoxy - D - homo - 5α - pregnan - 20 - one # 3# - acetoxy - 17a - alkanoyloxy - 19 - hydroxy- D - homopregn - 5 - en - 20 - one # 3# - acetoxy - 17a - alkanoyloxy - 19 - (2 - tetrahydropyranyloxy)- D - homopregn - 5 - en - 20 - one # 3# - hydroxy - 17a - alkanoyloxy - 19 - (2 - tetrahydropyranyloxy) - D - homopregn - 5 - en - 20 - one # 17a - alkanoyloxy - 19 - (2 - tetrahydropyranyloxy) - D - homopregn - 4 - ene - 3,20 - dione # 17a - alkanoyloxy - 19 - hydroxy - D - homopregn - 4 - ene- 3,20 dione # 17a - alkanoyloxy - 3,20 - dioxo - D - homopregn - 4 - en - 19 - al. D-Homoestrone methyl ether (X)#3-methoxy- D - homo - 19 - norpregna - 1,3,5(10),17a(20) - tetraene, # 3 - methoxy - D - homo - 19 - norpregna - 2,5(10)17a(20) - triene(XI) # D - homo - 19 - norpregna - 4,17a(20) - dien - 3 - one or D - homo - 19 - norpregna - 5(10),17a(20) - dien - 3 - one (XII), then XII # 3# - hydroxy - D - homo - 19 - norpregna - 5(10),17a(20) - diene # 3#,17a - dihydroxy - D - homo - 19 - norpregn - 5(10) - en - 20 - one. XI # 3,3 - Ethylene dioxy - D - homo - 19 - norpregna - 5(10),17a(20) - diene # 3,3 - ethylenedioxy - 17a - hydroxy - D - homo - 19 - norpregn- 5(10) - en - 20 - one # 3,3 - ethylenedioxy - 17a - hydroxy - 21 - acetoxy - D - homo - 19 - norpregn - 5(10) - en - 20 - one # 17a,21 - dihydroxy - D - homo - 19 - norpregn - 4 - ene - 3,20 - dione # the 21-mesylate thereof. X # 17aα - Chloro - 3 - methoxy - D - homoestra - 1,3,5(10) - triene - 17a# - carboxaldehyde # 3 - methoxy - D - homoestra - 1,3,5(10),17 - tetraene - 17a - carboxaldehyde (XIII) # 3,3 - ethylenedioxy - D - homo - 19 - norpregna - 5(10),17 - dien - 20 - one (XIV) # D - homo - 19 - norpregna- 4,17 - diene - 3,20 - dione # 3 - ethoxy - D - homo - 19 - norpregna - 3,5,17 - trien - 20 - one. The conversion XIII#XIV is effected by the successive actions of (i) MeLi, (ii) Na/NH 3 , (iii) ethylene glycol and (iv) CrO 3 . XIV # D - homo - 19 - norpregn - 4 - ene - 3,20 - dione # the ethyl enol ether thereof. Progestative compositions for oral, parenteral, topical and rectal administration comprise a compound I and a carrier.