Enantioselective synthesis of the antiinflammatory agent (-)-acanthoic acid

被引:71
作者
Ling, TT
Chowdhury, C
Kramer, BA
Vong, BG
Palladino, MA
Theodorakis, EA
机构
[1] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA
[2] Nereus Pharmaceut Inc, San Diego, CA 92121 USA
关键词
D O I
10.1021/jo0159035
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
An enantioselective synthesis of the potent antiinflammatory agent (-)-acanthoic acid (1) is described. The successful strategy departs from (-)-Wieland-Miescher ketone (10), which is readily available in both enantiomeric forms and constitutes the starting point toward a fully functionalized AB ring system of 1. Conditions were developed for a regioselective double alkylation at the C4 center of the A ring, which produced compound 32 as a single stereoisomer. Construction of the C ring of 1 was accomplished via a Diels-Alder reaction between sulfur-containing diene 43 and methacrolein (36), which after desulfurization and further functionalization yielded synthetic acanthoic acid. The described synthesis confirms the proposed stereochemistry of the natural product and represents a fully stereocontrolled entry into an underexplored class of biologically active diterpenes.
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页码:8843 / 8853
页数:11
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