Non-enzymatic synthesis of C -methylated fluostatins: discovery and reaction mechanism.

Two C -methylated fluostatins (FSTs) B3 (1) and B4 (2) were synthesized from flavin-mediated nonenzymatic epoxide ring-opening reactions of FST C. The structures of 1 and 2 were elucidated by HRESIMS, NMR, and ECD spectroscopic analyses. A subsequent 13 C labeling study demonstrated that the C -methyl groups of 1 and 2 were derived from DMSO and enabled the mechanistic proposal of a nonenzymatic C -methylation.