Synthesis and stereochemistry of 7β- and 7α-amino-, acetamido-, hemisuccinamido- and terephthalamido derivatives of testosterone

Article abstract of DOI:10.1016/0039-128X(81)90082-9

The reduction of 3-ethylenedioxy-7-oximino-5-androsten-17β-yl acetate and of its 17β-tetrahydropyranyl ether analog with sodium in ethanol, followed by thinlayer chromatography, allowed the isolation of the corresponding 17β-hydroxy- and 17β-tetrahydropyranyloxy-5-en-7β- and 7α-amines which were also characterized as 7-acetamides.The acylation of the two epimeric 17β-hydroxy-5-en-7-amines with succinic anhydride followed by selective saponification of the 17β-hemisuccinate group and diazomethane esterification, gave the corresponding 17β-hydroxy-5-en-7β- and 7α-hemisuccinamido methyl esters characterized also as 17β-acetates.On the other hand, the acylation of the two 17β-tetrahydropyranyloxy-5-en-7-amines with the acid chloride of terephthalic acid monomethyl ester led to the more rigid 7β- and 7α-terephthalamido methyl ester side-chains.The acidolysis of the 3-ethyleneketal protecting group of the preceding 5-en-7-N-acyl derivatives regenerated the 4-en-3-oxo function while the 17β-tetrahydropyranyl ether group was cleaved simultaneously into the 17β-alcohol.The four desired 7β- and 7α-hemisuccinamido- and terephthalamido carboxylic side-chain derivatives of 17β-hydroxy-4-androsten-3-one (testosterone) were finally obtained by saponification of the corresponding methyl esters.