Portal de Periódicos da CAPES

Efficient Asymmetric Synthesis of Biologically Important Tryptophan Analogues via a Palladium-Mediated Heteroannulation Reaction

2001; American Chemical Society; Volume: 66; Issue: 13 Linguagem: Inglês

10.1021/jo001679s

1520-6904

Chunrong Ma, Xiaoxiang Liu, Xiaoyan Li, Judith Flippen‐Anderson, Shu Yu, James M. Cook,

Catalytic C–H Functionalization Methods

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 Schöllkopf chiral auxiliary 19 employing diphenyl phosphate as the leaving group. The Schöllkopf 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.