Studies in polyphenol chemistry and bioactivity. 3. Stereocontrolled synthesis of epicatechin-4α,8-epicatechin, an unnatural isomer of the B-type procyanidins

A. P. Kozikowski, W. Tückmantel, Y. Hu

Research output: Contribution to journalArticlepeer-review

Abstract

Oligomeric procyanidins containing 4α-linked epicatechin units are rare in nature and have hitherto not been accessible through stereoselective synthesis. We report herein the preparation of the prototypical dimer, epicatechin-4α,8-epicatechin (6), by reaction of the protected 4-ketones 11a,b with aryllithium reagents derived by halogen/metal exchange from the awl bromides 26a,b. Removal of the 4-hydroxyl group from the resulting tertiary benzylic alcohols 27a,b was effected by tri-n-butyltin hydride and trifluoroacetic acid in a completely stereoselective manner, resulting in hydride delivery exclusively from the β face. If benzyl was chosen for protection of the 3-hydroxyls, all protective groups could subsequently be removed in a single step by hydrogenolysis, tert-Butyldimethylsilyl groups, on the other hand, permitted selective deprotection of the 3-hydroxyls in preparation for their subsequent acylation with tri-O-benzylgalloyl chloride. Only monogalloylation at the "bottom" 3-hydroxyl took place when 28c was acylated under the previously reported conditions, reflecting the increased steric hindrance of the "top" 3-hydroxyl group in 28c compared with its 4β,8-isomer 3. The preparation of compounds 14 and 17 containing phloroglucinol trimethyl ether in the 4α and 4β linkages to epicatechin is also described. The 8-position of the bromine atom in 19, previously conjectured in analogy to the structurally characterized tetramethyl ether 20, was confirmed by transformation of both compounds into the common derivative 25.

Original languageEnglish (US)
Pages (from-to)1287-1296
Number of pages10
JournalJournal of Organic Chemistry
Volume66
Issue number4
DOIs
StatePublished - Feb 23 2001

ASJC Scopus subject areas

  • Organic Chemistry

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