著者

砂塚 敏明 長光 亨 大村 智

出版者

社団法人 有機合成化学協会

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.56, no.6, pp.478-488, 1998-06-01

参考文献数

37

被引用文献数

2

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The first total synthesis of the microbial a-pyrone meroterpenoid, (+) -pyripyropene A (1), acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor, which is effective and concise convergent approach (14 steps, 9.3% overall yield), designed to afford easy access to both the natural products and a variety of analogs, has been achieved. The key step is the coupling reaction between a-pyronepyridine moiety (4) and the acid chloride of sesquiterpene moiety (3) in the presence of Lewis acid to construct ketone (2). The sesquiterpene moiety has been synthesized started from (+) -Wieland-Miescher ketons via stereoselective reductive formylation, palladium associated carbonylation, and allylic oxidation.<BR>(+) -Pyripyropene E (36) also has been synthesized from farnesyl acetate (9 steps, 9.6% overall yield). The convergent and stereoselective route exploited a biomimetic polyene cyclization as the key transformation.

著者

砂塚 敏明 長光 亨 大村 智

出版者

社団法人 有機合成化学協会

雑誌

有機合成化学協会誌 (ISSN:00379980)

巻号頁・発行日

vol.54, no.9, pp.740-751, 1996-09-01

参考文献数

48

被引用文献数

3

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A total synthesis of the microbial metabolite (+) -lactacystin (1), the first non-protein neurotrophic agent, has been achieved in 11 steps (14% overall yield) from 2 (R), 3 (S) -3-hydroxyleucine. The key steps in the elaboration of the lactam moiety include the stereoselective hydroxymethylation of oxazoline and an asymmetric allylboration of the aldehyde which introduce the hydroxyl and methyl substituents at C (6) and C (7).<BR>This new asymmetric approach furnished four stereoisomers of 3-hydroxyleucine as required starting material in high overall yield and enantiomeric purity.<BR>Furthermore, the construction of several active analogs and the structure-activity relationships of lactacystin are also described.