title: 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.
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 4beta-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)-(+)-alpha-methylbenzylamine salt. As a corollary, the selectivity of hydrogenolytic and solvolytic reactions of epicatechin-derived tetrasulfonates has been investigated.
authors.affiliation: Georgetown University Medical Center, Drug Discovery Program, Washington, DC 20007, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Kozikowski
authors.forename: W
authors.initials: W
authors.lastname: Tückmantel
authors.forename: C
authors.initials: C
authors.lastname: George
mesh_terms: D000478:Alkylation; D044946:Biflavonoids; D002392:Catechin / Q000737:chemistry*; D005419:Flavonoids; D009682:Magnetic Resonance Spectroscopy; D010084:Oxidation-Reduction; D010636:Phenols / Q000138:chemical synthesis*; D010654:Phenylbutyrates / Q000138:chemical synthesis*; D011108:Polymers / Q000138:chemical synthesis*; D044945:Proanthocyanidins; D013237:Stereoisomerism
chemical_list: C414100:2,4-diphenylbutanoic acid; D044946:Biflavonoids; D005419:Flavonoids; D010636:Phenols; D010654:Phenylbutyrates; D011108:Polymers; D044945:Proanthocyanidins; C479580:procyanidin B2; C017674:procyanidin; D002392:Catechin