Enantioselective Total Synthesis of Callipeltoside A

Callipeltoside A (1) was isolated from the lithistid sponge Callipelta sp. by Minale and co-workers in 1996.1 Preliminary biological assays indicated that this marine natural product exhibits cytotoxic activity against NSCLC-N6 human bronchopulmonary nonsmall-cell lung carcinoma and P388 cell lines.1 At the time this project was undertaken, the relative stereochemical relationships between the sugar and the macrolactone had been proposed on the basis of 2D-NMR studies. However, the relative stereochemistry of the chlorocyclopropyl side chain to the rest of the molecule and the absolute stereochemistry of callipeltoside A remained un-assigned. Recently, both Paterson2a and Trost2b have found that enantiomeric trans-chlorocyclopropane side chains were too remote to induce visible differences in the 1H- or 13C-NMR spectra of either the aglycons or the glycosylated macrolactones. However, the optical rotations of the two side chain stereoisomers were dramati