Total Synthesis of (-)-Hennoxazole A

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• 作者：Thomas E. Smith ; Wen-Hsin Kuo ; Emily P. Balskus ; Victoria D. Bock ; Jennifer L. Roizen ; Ashleigh B. Theberge ; Kathleen A. Carroll ; Tomoki Kurihara ; Jeffrey D. Wessler
• 刊名：Journal of Organic Chemistry
• 出版年：2008
• 出版时间：January 4, 2008
• 年：2008
• 卷：73
• 期：1
• 页码：142 - 150
• 全文大小：271K
• 年卷期：v.73,no.1(January 4, 2008)
• ISSN：1520-6904

文摘

An enantioselective, convergent total synthesis of the antiviral marine natural product (-)-hennoxazoleA is completed in 14 steps (longest linear sequence) from commercially available 4-methyloxazole-2-carboxylic acid. Synthesis of the C₁-C₁₅ pyran/bisoxazole fragment takes advantage of an aldol-likecoupling between a dimethyl acetal and an N-acetylthiazolidinethione for the direct, stereoselectiveinstallation of the C₈-methoxy-bearing stereocenter. A one-pot acetoacetate acylation/decarboxylation/cyclodehydration of another elaborate thiazolidinethione allows for rapid assembly of the pyran-basedring system. Synthesis of the C₁₅-C₂₅ skipped triene side chain fragment makes use of a [2,3]-Wittig-Still rearrangement for efficient installation of the trisubstituted Z-double bond. Key late-stage couplingof the two fragments is effected by deprotonation of the methyl group on the bisoxazole system usinglithium diethylamide, followed by alkylation with an allylic bromide side chain segment to form theC₁₅-C₁₆ bond.