Vitamin D3 active metabolites 24R,25-(OH)2-D3, 24S,25-(OH)2-D3 , and 1a,24R,25-(OH)3-D3 were synthesized by a convergent and stereoselective approach. In the synthetic route, the stereogenic center at C-24 was generated through ultrasonically induced aqueous conjugate addition of a iodide to Seebach’s dioxolanone, and the vitamin D triene system was constructed using the Lythgoe approach.
The synthesis, which is both short (seven steps from iodide) and efficient (32–40% overall yield), allows the preparation of large quantities of the metabolites and provides a novel example of a highly stereoselective reaction promoted by the zinc-copper couple in aqueous media.