Studies in polyphenol chemistry and bioactivity. 2. Establishment of interflavan linkage regio- and stereochemistry by oxidative degradation of an O-alkylated derivative of procyanidin B2 to (R)-(-)-2,4-diphenylbutyric acid

Alan P. Kozikowski, Werner Tückmantel, Clifford George

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Abstract

The assignment of interflavan bond regio- and stereochemistry in oligomeric proanthocyanidins has in the past relied on empirical spectroscopic techniques which are influenced by the conformation of the C rings. Only recently was the 4,8-regiochemistry of procyanidin B2 (3b) firmly established by 2-dimensional NMR methods. We describe herein the proof of 4β-stereochemistry in 3b by oxidative degradation of the derivative 3d bearing differential (O-benzyl and O-methyl) protecting groups in its 'top' and 'bottom' epicatechin moieties, to (R)-(-)-2,4-diphenylbutyric acid. The key elements of the degradative process are (1) removal of the C-3 alcohol functions through a modified Barton deoxygenation employing hypophosphorous acid as the reducing agent; (2) deprotection of the 'top' unit by hydrogenolysis, followed by exhaustive aryl triflate formation with N,N-bis-(trifluoromethanesulfonyl)aniline and DBU in DMF; (3) hydrogenolytic deoxygenation of the 'top' unit over Pearlman's catalyst with concomitant scission of the O-C2 bond; (4) selective oxidation of the 'bottom' unit with NaIO4/RuCl3. The hitherto unreported absolute configuration of (-)-2,4-diphenylbutyric acid was established as R by X-ray crystal structure analysis of the (R)-(+)-α-methylbenzylamine salt. As a corollary, the selectivity of hydrogenolytic and solvolytic reactions of epicatechin-derived tetrasulfonates has been investigated.

Original languageEnglish (US)
Pages (from-to)5371-5381
Number of pages11
JournalJournal of Organic Chemistry
Volume65
Issue number17
DOIs
StatePublished - Aug 25 2000

ASJC Scopus subject areas

  • Organic Chemistry

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