Nucleosteroids: Reaction of activated purine bases with steroidal reactive centers

The reaction of 16α, 17α-epoxy-3β-hydroxy-5-pregnen-20-one with 6-methyl thiopurine activated with sodium hydride leads to the coupling of the purine base with the carbonyl group at C-20 to give a steroidal nucleoside analog, which is termed “nucleosteroid.” In the presence of excess of purine, a parallel reaction occurs in which the oxirane ring is opened, presumably by nucleophilic attack of an intermediate C-20 oxyanion, and yields as the main product of reaction on oligomeric mixture of nucleosteroid units linked together by ether linkages. Analogous reactions conducted with 3β-hydroxy-5-pregnen-20-one and with 3β,17α-dihydroxy-5-pregnen-20-one gave minor amounts or only traces of the corresponding coupling adduct, and oligomerization did not occur. This behavior is interpreted in terms of the conformational differences showed by the different steroids to the attack by the purine.