A Unified Approach to ent-Atisane Diterpenes and Related Alkaloids: Synthesis of (鈭?-Methyl Atisenoate, (鈭?-Isoatisine, and the Hetidine Skeleton

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• 作者：Emily C. Cherney ; Justin M. Lopchuk ; Jason C. Green ; Phil S. Baran
• 刊名：Journal of the American Chemical Society
• 出版年：2014
• 出版时间：September 10, 2014
• 年：2014
• 卷：136
• 期：36
• 页码：12592-12595
• 全文大小：421K
• ISSN：1520-5126

文摘

A unified approach to ent-atisane diterpenes and related atisine and hetidine alkaloids has been developed from ent-kaurane (鈭?-steviol (1). The conversion of the ent-kaurane skeleton to the ent-atisane skeleton features a Mukaiyama peroxygenation with concomitant cleavage of the C13鈥揅16 bond. Conversion to the atisine skeleton (9) features a C20-selective C鈥揌 activation using a Su谩rez modification of the Hofmann鈥揕枚ffler鈥揊reytag (HLF) reaction. A cascade sequence involving azomethine ylide isomerization followed by Mannich cyclization forms the C14鈥揅20 bond in the hetidine skeleton (8). Finally, attempts to form the N鈥揅6 bond of the hetisine skeleton (7) with a late-stage HLF reaction are discussed. The synthesis of these skeletons has enabled the completion of (鈭?-methyl atisenoate (3) and (鈭?-isoatisine (4).