Synthesis of Myrocin G, the Putative Active Form of the Myrocin Antitumor Antibiotics

J Am Chem Soc. 2018 Nov 28;140(47):16058-16061. doi: 10.1021/jacs.8b10891. Epub 2018 Nov 16.


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 isolated from reactions of 1 with excess benzenethiol. This work provides the first direct access to the diosphenol 7, sets the stage for elucidating the mode of interaction of the myrocins with DNA, and provides a foundation for the synthesis of other pimarane diterpenes.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Abietanes / chemical synthesis*
  • Antibiotics, Antineoplastic / chemical synthesis*
  • Cyclization
  • Stereoisomerism


  • Abietanes
  • Antibiotics, Antineoplastic