Unknown

Dataset Information

0

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


ABSTRACT: 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-?-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.

SUBMITTER: Economou C 

PROVIDER: S-EPMC7001008 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC7017366 | BioStudies
1000-01-01 | S-EPMC6274167 | BioStudies
2012-01-01 | S-EPMC3347013 | BioStudies
2018-01-01 | S-EPMC6117666 | BioStudies
2019-01-01 | S-EPMC6746854 | BioStudies
2015-01-01 | S-EPMC4703074 | BioStudies
2020-01-01 | S-EPMC7273749 | BioStudies
2011-01-01 | S-EPMC3057937 | BioStudies
2008-01-01 | S-EPMC2628296 | BioStudies
2015-01-01 | S-EPMC4584356 | BioStudies