1. Efficient synthesis of the A-ring phosphine oxide building block useful for 1 alpha,25-dihydroxy vitamin D(3) and analogues.
- Author
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Daniewski AR, Garofalo LM, Hutchings SD, Kabat MM, Liu W, Okabe M, Radinov R, and Yiannikouros GP
- Subjects
- Catalysis, Chromatography, Thin Layer, Cyclohexane Monoterpenes, Heptanes chemical synthesis, Heptanes chemistry, Magnetic Resonance Spectroscopy, Molecular Structure, Monoterpenes, Oxides chemical synthesis, Oxides chemistry, Phosphines, Phosphinic Acids chemistry, Silanes chemical synthesis, Silanes chemistry, Stereoisomerism, Terpenes chemistry, Vitamin A chemistry, Phosphinic Acids chemical synthesis, Vitamin A analogs & derivatives, Vitamin A chemical synthesis
- Abstract
The 1 alpha-hydroxy A-ring phosphine oxide 1, a useful building block for vitamin D analogues, was synthesized from (S)-carvone in nine synthetic operations and a single chromatographic purification in 25% overall yield. The synthesis features two novel efficient synthetic transformations: the Criegee rearrangement of alpha-methoxy hydroperoxyacetate 10 in methanol to obtain directly the desired secondary 3 beta-alcohol 11 and the highly chemo- and stereoselective isomerization of dieneoxide ester (E)-7 to the 1 alpha-allylic alcohol with an exocyclic double bond (E)-8. Further insight into the selectivity control of the latter rearrangement was obtained from the reactions of (Z)-epimeric substrates. The new synthetic approach leading to the 1 alpha-hydroxy epimers complements our previously reported synthesis of the corresponding 1 beta-epimers, thus producing all stereoisomers of these versatile building blocks efficiently from carvone.
- Published
- 2002
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