GB934714A - 1-methyl aromatic steroids - Google Patents

Abstract

The invention comprises (1) a process for preparing steroids having an aromatic ring A, a 1-methyl group and a 3-acyloxy group wherein a D 1,4-3,11-diketo-steroid is reacted with a carboxylic acid anhydride in the presence of a strong acid catalyst, either under mild conditions to yield a 1-methyl-3-acyloxy-D 1,3,5(10)-11-keto-steroid having a 9a -hydrogen atom or under forcing conditions to yield a 1-methyl-3,11-di-acyloxy-D 1,3,5(10),9(11) -steroid; (2) the new steroids of the formula <FORM:0934714/IV(a)/1> wherein R1 is a ketonic oxygen atom or a dihydroxy-acetone side chain or a mono- or di-ester thereof and R2 is a hydrogen atom or an acyl group, the 9-hydrogen atom having the a - or b -configuration but not the a -configuration when R1 is a dihydroxy-acetone side chain or a di-ester thereof; and (3) the new steroid 3,11,17a ,21-tetra-acetoxy-1-methyl-19-norpregna-1,3,5(10),9(11) -tetra-en-20-one. The starting material in process (1) preferably has the formula <FORM:0934714/IV(a)/2> in which R1 is as defined above, keto groups in it being protected if necessary, and the process may then be combined with the further steps of hydrolysing the 3-acyloxy-9a -#H-11-ones to the 3-hydroxy compounds and with the further step of treating either of these with a strong acid or base to yield 3-hydroxy-9b -#H-11-ones or of reacting the 3-acyloxy-9a -#H-11-ones with a carboxylic acid anhydride in the presence of a strong acid catalyst under forcing conditions to yield 3,11-diacyloxy-D 9(11)-steroids which may then be hydrolysed to yield the 3-hydroxy-9b -#H-11-ones. It is stated that although the 9b -epimer is the predominant product of these processes, some of the 9a -epimer is usually also formed. Mild conditions are defined as low concentrations of catalyst and/or short reaction times and/or low reaction temperatures, but it is stated that whatever conditions are employed, a mixture of products is frequently obtained, these being separated by chromatography. Keto groups may be protected by semicarbazone formation or formation of bis-methylenedioxy derivatives. Unprotected keto groups are enolacylated in the process involving acid anhydrides and free hydroxy groups are generally acylated. Hydrolysis of 3-acyloxy compounds may simultaneously involve hydrolysis of 17- and 21-acyloxy groups. Hydroxy groups may subsequently be reacylated. Acid anhydrides referred to are those of acetic, propionic and butyric acids, and strong acids mentioned are sulphuric, perchloric and toluene-p-sulphonic. Detailed examples are given. The Provisional Specification describes steroids of the formula <FORM:0934714/IV(a)/3> where R is hydrogen or an acyl group; R1 is hydrogen or an alkyl group; R2 is hydrogen, a hydroxy or acyloxy group, a ketonic oxygen atom, an acetyl group, a hydroxy or acyloxy-acetyl group, a dihydroxy-acetone chain or a mono- or di-ester thereof; R3 is hydrogen or a hydroxy or alkyl group and R4 is hydrogen or an alkyl group or a fluorine atom, the 9-hydrogen atom having the a - or b -configuration.