GB1354164A - Steroido-oxazolines and processes for their production - Google Patents

Abstract

1354164 Steroido-oxazolines GRUPPO LEPETIT SpA 7 July 1971 [9 July 1970] 31898/71 Heading C2U Novel steroids of the formula wherein X is H or halogen; Y is O or H(OH); or X and Y together represent a further bond between the 9- and 11-carbon atoms; R is H or acyl; and R<SP>1</SP> is C 1-5 alkyl, are prepared by heating a steroid of the formula (wherein Ac is the acyl radical of a C 2-6 alkanoic acid) with a weak base in the presence of a polar aprotic solvent to form a steroid of the formula hydrogenating this to remove the #<SP>15</SP>-double bond, cyclizing the α-epimer or the α- and #- epimeric mixture of the thus-obtained 16-acylaminopregnane and then converting the [16α, 17α-d]-fused oxazoline-steroid produced to the required product by known methods of introducing #<SP>1</SP>- and #<SP>4</SP>-double bonds, a 3-keto group and the required moieties X, Y and R. An 11- keto group may be reduced to an 11#-hydroxy group, the 20-keto group being protected and subsequently released, and the 11#-ol formed may be dehydrated to a 9(11)-ene. If the 20- keto group is protected by semicarbazone formation, hydrolysis by treatment with hydrochloric acid results not only in release of the 20- keto group but also in dehydration to the 9(11)- ene. Also, in reduction to the 11#-ol if a strongly basic aqueous solution of sodium borohydride is used hydrolysis of the 3#-acyloxy group also takes place. A 21-acetoxy group may be introduced by 21-iodination followed by exchange between the iodine atom and an acetate ion. The resulting product may be oxidized to a 3- ketone into which #<SP>1</SP>- and #<SP>4</SP>-double bonds may be introduced by bromination and dehydrobromination. A #<SP>1,4,9(11)</SP>-triene may be converted into a 9α-halo-11#-ol by treatment with NBA to give a 9α-bromo-11#-ol and, when required, dehydrohalogenation of this to give a 9#, 11#-epoxide and reaction of this with HF to give a 9α-fluoro-11#-ol. 16# - chloroamino - 3#,17α - di-alkanoyloxy-5α- pregnane-11,20-diones are prepared by reducing 3#,17α - di - alkanoyloxy - 16# - azido - 5α- pregnane-11,20-diones (prepared by acylation of the diols) to the corresponding 16#-amino compounds and then chlorinating these. 5α-pregnane 16#-azido-3#,17α-diol-11,20-dione is prepared by reacting 5α - pregnane - 16α,17α - epoxy - 3# - ol- 11,20-dione (in turn prepared by epoxidation of the corresponding 16-ene) with sodium azide.