Amino-steroids. Part II. 6-Amino-androstanes and -pregnanes

Abstract

Condensation of 3β-acetoxy-5α,6α-epoxy-androstanes and -pregnanes with ammonia and primary and secondary amines, and subsequent alkaline hydrolysis, gives 6β-amino-3β,5α-dihydroxy-steroids; water catalyses the epoxide cleavage. When condensation with ammonia is carried out in aqueous dioxan solution a 6β-acetamido-5α-hydroxy-steroid is obtained. Condensation of a mixture of 5α,6α- and 5β,6β-epoxides with aqueous morpholine at 115° gives the cleavage product of the α-oxide only and the β-oxide is recovered unchanged. Condensation of 5β,6β-epoxy-3β-hydroxyandrostan-17-one with piperidine and morpholine at 190° gives abnormal ring opening to the diequatorial 6α-amino-3β,5β-dihydroxyandrostan-17-one, the infrared spectra of which show intramolecular hydrogen bonding between the 3β-hydroxyl group and the oxygen atom of the 5β-hydroxyl group, which in turn bonds to the 6α-nitrogen atom. Oxidation of 3β,5α-dihydroxy-6β-piperidinoandrostan-17-one or the 5β,6α-epimer, and subsequent dehydration of the product, gives 6α-piperidinoandrost-4-ene-3,17-dione.