Stereoselective convergent synthesis of 24,25-dihydroxyvitamin D3 metabolites: a practical approach

Pérez Sestelo, J.; Cornella, I.; de Uña, O.; Mouriño, A.; Sarandeses, L. A.


Chem. Eur. J. 2002, 8, 2747–2752 (DOI: 10.1002/1521-3765(20020617)8:12<2747::AID-CHEM2747>3.0.CO;2-J).

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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.