Convergent syntheses of 9-deoxy-12-phenylthioprostanoids and 9-deoxy-Δ8(12)-PGD1 derivatives

Abstract

Conjugate additions of organolithium or organomagnesium compounds, mediated by copper(I), to 2-phenylthiocyclopent-2-enone, and of enolates of the initial adducts to 2-phenylsulphinyloct-1-en-3-one, provided convergent constructions of the prostanoid framework. Stereospecific introduction of the Δ¹³ double bond by sulphoxide elimination, the elimination of benzenesulphenic acid from 12β-phenylsulphinylprostanoids at room temperature, and the chemoselective reduction of 11-oxo-13-en-15-ones to 11-oxo-13-en-15-ols, provided 9-deoxy-12-phenylthioprostaglandin D₁ analogues and 9-deoxy-Δ⁸⁽¹²⁾-prostaglandin D₁, derivatives. The conjugate additions, and the propensity for ether formation during the Meerwein–Ponndorf–Verley reduction of the 13-en-15-ones, were influenced by the presence of remote oxygen substitutents in the incipient α-side-chain.