Journal of Organic Chemistry 2002-07-12

Efficient total synthesis of pulchellalactam, a CD45 protein tyrosine phosphatase inhibitor.

Wen-Ren Li, Sung Tsai Lin, Nai-Mu Hsu, Meei-Shiou Chern

Index: J. Org. Chem. 67(14) , 4702-6, (2002)

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Abstract

A new approach to a CD45 protein tyrosine phosphatase inhibitor, pulchellalactam, is described. The key step of the sequence involves addition and elimination of an enolic lactam in a single step and 70% yield, employing an organocuprate reagent. The resulting alpha,beta-unsaturated lactam could be condensed with isobutyraldehyde to produce Z-pulchellalactam or converted into siloxypyrrole, which was subjected to the BF(3) x Et(2)O-promoted coupling reaction with isobutyraldehyde to afford E-pulchellalactam after E1-cB elimination and TFA deprotection. This first total synthesis afforded Z-pulchellalactam in six steps and 32% overall yield from Boc-glycine. The same sequence of reactions could also be applied to the liquid- or solid-phase synthesis of trifunctionalized pulchellalactam derivatives.