Total Synthesis of Chloropeptin II (Complestatin) and Chloropeptin I
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- 作者：Joie Garfunkle ; F. Scott Kimball ; John D. Trzupek ; Shinobu Takizawa ; Hiroyuki Shimamura ; Masaki Tomishima ; Dale L. Boger
- 刊名：Journal of the American Chemical Society
- 出版年：2009
- 出版时间：November 11, 2009
- 年：2009
- 卷：131
- 期：44
- 页码：16036-16038
- 全文大小：195K
- 年卷期：v.131,no.44(November 11, 2009)
- ISSN：1520-5126
文摘
The first total synthesis of chloropeptin II (1, complestatin) is disclosed. Key elements of the approach include the use of an intramolecular Larock indole synthesis for the initial macrocyclization, adopting conditions that permit utilization of a 2-bromoaniline, incorporating a terminal alkyne substituent (−SiEt3) that sterically dictates the indole cyclization regioselectivity, and benefiting from an aniline protecting group (−Ac) that enhances the atropdiastereoselectivity and diminishes the strained indole reactivity toward subsequent electrophilic reagents. Not only did this key reaction provide the fully functionalized right-hand ring system of 1 in superb conversion (89%) and good atropdiastereoselectivity (4:1 R:S), but it also represents the first reported example of what will prove to be a useful Larock macrocyclization strategy. Subsequent introduction of the left-hand ring system enlisting an aromatic nucleophilic substitution reaction for macrocyclization with biaryl ether formation completed the assemblage of the core bicyclic structure of 1. Intrinsic in the design of the approach and by virtue of the single-step acid-catalyzed conversion of chloropeptin II (1) to chloropeptin I (2), the route also provides a total synthesis of 2.