Solid-Phase Synthesis of Oxathiocoraline

Significance

The first solid-phase total synthesis of oxathiocoraline 1, a member of the quinoxaline antibiotic family, was achieved. Thus, from Wang resin 2 and Fmoc-Gly-OH, polymer-supported 3 was synthesized in 8 steps (89% purity). The key disulfide formation (dimerization) was performed with I₂ in DMF to give 4. Cleavage of the dimer from the resin with concomitant cleavage of the Boc group, subsequent bismacrolactamization followed by incorporation of the heterocyclic unit afforded oxathiocoraline 1. Crude 1 was obtained in 7% overall yield after purification by semipreparative HPLC.