Complete Structure and Total Synthesis of Streptospherin A, a Cancer Stem Cell Inhibitor

Streptospherin A (1), isolated from the actinomycete Streptomyces sp. KUSC-240 strain, inhibits cancer stem cell sphere formation. The planar structure of 1 and the relative configurations of C3, C5, and C7 in the pyran ring were previously assigned as (3R*, 5S*, 7S*). However, the remaining relative stereochemistry and absolute configuration of 1 have not been determined because of limited sample availability. In this study, the relative configuration at C2 was established by synthesizing model compounds 15a/15b and comparing their NMR spectra with that of 1. The absolute configuration of 1 was then confirmed by total synthesis. Synthetic 1 exhibited inhibitory activity of cancer stem cell sphere formation equivalent to that of the natural 1.