Synthesis and Biological Evaluation of (2S,2′S)-Lomaiviticin A
- 7 January 2021
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of the American Chemical Society
- Vol. 143 (2), 1126-1132
- https://doi.org/10.1021/jacs.0c11960
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.Keywords
Funding Information
- Yale University
- National Institute of General Medical Sciences (R35-GM131913)
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