biostudies-literatureEconomou CYale UniversityNCI NIH HHSNational Institutes of HealthNIGMS NIH HHS16058-16061https://www.ebi.ac.uk/biostudies/studies/S-EPMC7001008biostudies-literatureUnknown140(47)The antiproliferative antimicrobial fungal metabolites known as the myrocins have been proposed to cross-link DNA by double nucleotide addition. However, the nature of the DNA-reactive species is ambiguous, as myrocins have been isolated as functionally distinct 5-hydroxy-γ-lactone and diosphenol isomers. Based on literature precedent, we hypothesized that the diosphenol 7 (assigned here the trivial name myrocin G) is the biologically active form of the representative isolate (+)-myrocin C (1). To probe this, we developed a short enantioselective route to 7. A powerful fragment-coupling reaction that forms the central ring of the target in 38% yield and in a single step was developed. In support of our hypothesis, 7 was efficiently transformed to the bis(sulfide) 6, a product previously isJournal of the American Chemical SocietySynthesis of Myrocin G, the Putative Active Form of the Myrocin Antitumor Antibiotics.PMC7001008R35 GM131913F31 CA213964T32 GM067543Herzon SBEconomou CTomanik MfalseSynthesis of Myrocin G, the Putative Active Form of the Myrocin Antitumor Antibiotics.The antiproliferative antimicrobial fungal metabolites known as the myrocins have been proposed to cross-link DNA by double nucleotide addition. However, the nature of the DNA-reactive species is ambiguous, as myrocins have been isolated as functionally distinct 5-hydroxy-γ-lactone and diosphenol isomers. Based on literature precedent, we hypothesized that the diosphenol 7 (assigned here the trivial name myrocin G) is the biologically active form of the representative isolate (+)-myrocin C (1). To probe this, we developed a short enantioselective route to 7. A powerful fragment-coupling reaction that forms the central ring of the target in 38% yield and in a single step was developed. In support of our hypothesis, 7 was efficiently transformed to the bis(sulfide) 6, a product previously is2018-01-01T00:00:00Z2018 Nov2025-04-19T09:37:55.598Z2020-10-29T12:55:09ZS-EPMC70010083041554010.1021/jacs.8b10891