Efficient asymmetric synthesis of biologically important tryptophan analogues via a palladium-mediated heteroannulation reaction

被引:180
作者
Ma, CR
Liu, XX
Li, XY
Flippen-Anderson, J
Yu, S
Cook, JM [1 ]
机构
[1] Univ Wisconsin, Dept Chem, Milwaukee, WI 53201 USA
[2] USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA
关键词
D O I
10.1021/jo001679s
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A novel and concise synthesis of optically active tryptophan derivatives was developed via a palladium-catalyzed heteroannulation reaction of substituted o-iodoanilines with an internal alkyne. The required internal alkyne 14a or 25 was prepared in greater than 96% de via alkylation of the Schollkopf chiral auxiliary 19 employing diphenyl phosphate as the leaving group. The Schollkopf chiral auxiliary was chosen here for the preparation of L-tryptophans would be available from D-valine while the D-isomers required for natural product total synthesis would originate from the inexpensive L-valine (300-g scale). Applications of the palladium-catalyzed heteroannulation reaction were extended to the first asymmetric synthesis of L-isotryptophan 38 and L-benz[f]tryptophan 39. More importantly, the optically pure 6-methoxy-D-tryptophan 62 was prepared by this protocol on a large scale (> 300 g). This should permit entry into many ring-A oxygenated indole alkaloids when coupled with the asymmetric Pictet-Spengler reaction. In addition, an improved total synthesis of tryprostatin A (9a) was accomplished in 43% overall yield employing this palladium-mediated process.
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页码:4525 / 4542
页数:18
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