Synthesis of leucascandrolide A*
Ying Wang, Jelena Janjic, and Sergey A. Kozmin
Department of Chemistry, University of Chicago, 5735 South Ellis Avenue, Chicago, IL 60637, USA
Abstract: This paper describes a convergent and stereocontrolled synthesis of leucascandrolide A, a marine natural product that exhibits potent growth inhibition of mammalian and yeast cells. The approach features a substrate-directed relay of the stereochemical information via a series of highly diastereoselective transformations. Spontaneous macrolactolization discovered during this synthetic exercise has provided an unprecedented access to this marine macrolide and demonstrates a new tactic for assembling large-ring systems based on the thermodynamic preference of hemiacetalization.
Keywords: leucascandrolide; macrolactolization; hydrosilylation; natural products; diastereocontrol.
*An issue of reviews and research papers based on lectures presented at the 15th International Conference on Organic Synthesis (ICOS-15), held in Nagoya, Japan, 1-6 August 2004, on the theme of organic synthesis. Other presentations are published in this issue, pp. 1087-1296.