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

被引:43
作者
Kozikowski, AP
Tückmantel, W
George, C
机构
[1] Georgetown Univ, Med Ctr, Drug Discovery Program, Washington, DC 20007 USA
[2] USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA
关键词
D O I
10.1021/jo000485+
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
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 B-2 (3b) firmly established by 2-dimensional NMR methods. We describe herein the proof of 4 beta-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.
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页码:5371 / 5381
页数:11
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