Stereoselective convergent synthesis of 24-substituted metabolites and analogues of vitamin D.

Cornella, I.; Suárez, R. M.; Mouriño, A.; Pérez Sestelo, J.; Sarandeses, L. A.


J. Steroid Biochem. Mol. Biol. 2004, 89-90, 19–23 (DOI: 10.1016/j.jsbmb.2004.03.045).

trigger text
hidden content

The synthesis of vitamin D3 active metabolites [24R,25-(OH)2-D3, 24S,25-(OH)2-D3 and 1α,24R,25-(OH)3-D3] and the first 24-aminovitamin D3 derivatives [24S-benzoylamino-25-OH-D3 and 24S-benzoylamino-1α,25-(OH)2-D3] are reported. The stereogenic center at C-24 was generated through ultrasonically induced aqueous conjugate addition of a iodide to a dioxolanone or to a oxazolidinone. The vitamin D triene system was constructed using the Lythgoe approach. The synthetic route, which is both short (6 or 7 steps from starting iodide) and efficient (32–45% overall yield), constitutes a practical method for the preparation of 24-functionalized metabolites and analogues of vitamin D3. The ultrasonically induced conjugate addition in the key step provides a novel example of a highly stereoselective reaction promoted by the zinc–copper couple in aqueous media.