Work

Synthesis and Biological Evaluation of (2S,2′S)-Lomaiviticin A

Year: 2021

Type: article

Abstract: (−)-Lomaiviticin A ( 1 ) is a genotoxic C 2 -symmetric metabolite that arises from the formal dimerization of two bis(glycosylated) diazotetrahydrobenzo[ b ]fluorenes. Here we present a synthesis of the monomer 17 and its coupling to form (2 S,2′ S )-lomaiviticin A ( 4 ), an unnatural diastereomer of 1 . (2 S,2′ S )-Lomaiviticin A ( 4 ) is significantly less genotoxic, a result we attribute to changes in the orientation of the diazofluorene and carbohydrate residues, relative to 1 . These data bring the importance of the configuration of the conjoining bond to light and place the total synthesis of 1 itself within reach.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.0c11960

Authors: Miho Kaneko, Zhenwu Li, Matthew Burk, Laureen Colis, Seth B. Herzon

Institution: Yale University

Language: English

Topic: Synthesis and pharmacology of benzodiazepine derivatives

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: Yale University, National Institute of General Medical Sciences

Award: Synthetic and translational studies of antitumor and antimicrobial natural products.