Total synthesis of (+)-trichostatins A and C via the O-directed dialkylacetylene free radical hydrostannation reaction

(+)-Trichostatin C (TSC) is natural glucopyranosyl hydroxylamine derivatives of TSA with O-β-D-glucopyranosylhydroxylamine. We became interested in developing an enantioselective total synthesis of the (+)-TSA and (+)-TSC molecule to potentially show off the significant utility of the O-directed free radical hydrostannation of disubstituted alkynes for constructing trisubstituted alkenes in target molecules that contain a dialkylaniline ring system.

Such a synthetic approach to (+)-TSA might potentially be adaptable to the creation of novel analogues that could be screened for their HDAC inhibitory effects, which are of potential therapeutic relevance to the treatment of diseases ranging from cancer right through to SARS-CoV-2 (COVID-19). Our new total syntheses of (+)-trichostatins A and C have been completed in high optical purity (97% ee), so confirming that the O-directed free radical hydrostannation with Ph3SnH/cat.