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

ABSTRACT: (-)-Lomaiviticin A (1) is a genotoxic C₂-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 (2S,2'S)-lomaiviticin A (4), an unnatural diastereomer of 1. (2S,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.

SUBMITTER: Kaneko M

PROVIDER: S-EPMC8174553 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Kaneko Miho M Li Zhenwu Z Burk Matthew M Colis Laureen L Herzon Seth B SB

Journal of the American Chemical Society 20210107 2

(-)-Lomaiviticin A (1) is a genotoxic C2-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 (2S,2'S)-lomaiviticin A (4), an unnatural diastereomer of 1. (2S,2'S)-Lomaiviticin A (4) is significantly less genotoxic, a result we attribute to changes in the orientation of th ...[more]

PMID: 33410680

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