Preparation of 2-hydroxy A-ring precursors for synthesis of vitamin D3 analogues from lyxose

Abstract

Syntheses of vitamin D3 (VD3) A-ring precursors 1b, 2, and 3, which are precursors for 2-hydroxy or 2-alkoxy 1α-OH-VDs, via a common intermediate enyne 1a were carried out starting from lyxose. From 1a, exo-methylene halide 2, which is an A-ring intermediate for the synthesis of 2-alkoxy vitamin D3, was synthesized by a Ti(II)-mediated cyclization. Phosphine oxide 3a and benzothiazolylsulfone 3b, which are 19-nor-type A-ring intermediates of 2-alkoxy vitamin D, were prepared by a Ru-catalyzed metathesis followed by a Ni-catalyzed 1,4-selective hydroboration reaction.