The chemistry of the taxane diterpene: Stereoselective reductions of taxanes

Gunda I. Georg, Geraldine C.B. Harriman, Apurba Datta, Syed Ali, Zacharia Cheruvallath, Dinah Dutta, David G. Vander Velde, Richard H. Himes

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Abstract

Stereoselective reductions of taxanes are detailed. Chelation- controlled reductions employing SmI2 are described for the stereoselective reduction of the 9-keto functionality of the diterpene moiety of several taxanes. In all cases the 9β-hydroxy stereochemistry was obtained exclusively. In addition to C9 reduction, partial C10-deoxygenation via β- elimination was observed. Lower reaction temperatures favored the reduction pathway without β-elimination. Acetic acid as the proton source gave higher yields and cleaner reaction products. This chemistry provided access to taxanes with 9β-hydroxy, 10β-hydroxy stereochemistry. Evidence is presented, suggesting that chelation of samarium with the 7β-hydroxyl group is required for the reduction of the C9 ketone moiety. The synthesis of paclitaxel analogues, possessing the 9α-hydroxy, 10α-hydroxy stereochemistry was also achieved. Reduction of the 10-ketone group of 10- oxopaclitaxel employing NaBH4 produced 10-deacetyl-10-epipaclitaxel stereoselectively. Using an excess of NaBH4 in this reaction gave exclusively the 9α-hydroxy, 10α-hydroxy paclitaxel analogue.

Original languageEnglish (US)
Pages (from-to)8926-8934
Number of pages9
JournalJournal of Organic Chemistry
Volume63
Issue number24
DOIs
StatePublished - Nov 27 1998

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