Synthesis of 14-deoxy-14α-strophanthidin

Abstract

A seventeen step synthesis of 3β,5-dihydroxy-19-oxo-5β,14α-card-20(22)-enolide (II, title compound) from 3β-benzoyloxy-5-pregnen-20-one (IV) is described. Characteristic features of this approach are the protection of the 19-hydroxy group as methyl ether, recovery of the hydroxyl and the introduction of 5β-hydroxyl on the basis of neighboring group participation. The 19-hydroxy group was regenerated in XIV by a two-step process: Addition of hypobromous acid to the 5,6-double bond leads to the 5α,6α-bromonium ion XV, which is cleaved with 5(O)n participation of the 19-methoxyl group to the cyclic ether XVI, the latter being converted to the 19-hydroxy derivative XVII by treatment with zinc and acetic acid. The 5β-hydroxy group was introduced by hypobromous acid addition to the 5,6-unsaturated 19-formate XVIII which proceeds with 6(O)π,n participation of the formate group (XVIII → XIX → XX).