A short stereoselective synthesis of prepiscibactin using a SmI2-mediated Reformatsky reaction and Zn2+-induced asymmetric thiazolidine formation.

Abstract

Prepiscibactin (1) is a possible intermediate in the biosynthesis of piscibactin, the siderophore responsible for the iron uptake of the bacterium Photobacterium damselae subsp. piscicida, the aethiological agent of fish pasteurellosis. Compound 1 was synthesized by a convergent approach starting from L-/D-cysteine and 2-hydroxybenzonitrile. The key steps were a highly diastereoselective SmI2-mediated Reformatsky reaction and Zn(2+)-induced asymmetric thiazolidine formation followed by lactamization. The absolute configuration 9R,10S,12R,13S was established for 1, and this confirmed the previous relative stereochemistry proposed on the basis of NOE and computational methods.