Efficient synthesis of the A-ring phosphine oxide building block useful for 1 alpha,25-dihydroxy vitamin D(3) and analogues

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 Crieg...

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Bibliographic Details
Published in:Journal of organic chemistry 2002-03, Vol.67 (5), p.1580-1587
Main Authors: Daniewski, Andrzej R, Garofalo, Lisa M, Hutchings, Stanley D, Kabat, Marek M, Liu, Wen, Okabe, Masami, Radinov, Roumen, Yiannikouros, George P
Format: Article
Language:English
Subjects:
Catalysis
Chromatography, Thin Layer
Heptanes - chemical synthesis
Heptanes - chemistry
Magnetic Resonance Spectroscopy
Molecular Structure
Monoterpenes
Oxides - chemical synthesis
Oxides - chemistry
Phosphines
Phosphinic Acids - chemical synthesis
Phosphinic Acids - chemistry
Silanes - chemical synthesis
Silanes - chemistry
Stereoisomerism
Terpenes - chemistry
Vitamin A - analogs & derivatives
Vitamin A - chemical synthesis
Vitamin A - chemistry
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Summary: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.
ISSN:0022-3263