Syntheses of Cyclopropyl Analogues of Disorazoles A and B and Their Thiazole Counterparts.

J Org Chem

Department of Chemistry, BioScience Research Collaborative , Rice University, 6100 Main Street , Houston , Texas 77005 , United States.

Published: October 2018

AI Article Synopsis

  • Modular syntheses have successfully replaced epoxide moieties in disorazoles A and B analogues with cyclopropyl units, focusing on structure-activity relationships.
  • The synthesis was extended to thiazole counterparts, utilizing key reactions like Yamaguchi esterification and Cu/Pd-catalyzed cross-coupling.
  • Ongoing research aims to explore the biological potential of these analogues for developing targeted cancer treatments, specifically for antibody-drug conjugates.

Article Abstract

Modular syntheses of disorazoles A and B analogues in which the epoxide moieties of the natural products were replaced with cyclopropyl units have been achieved. Targeted as part of a structure-activity relationships study, these syntheses were successfully extended to the thiazole counterparts of these analogues. The retrosynthetically defined fragments were assembled through Yamaguchi esterification, Cu/Pd-catalyzed cross-coupling, Yamaguchi macrolactonization, and Cu-catalyzed cross-coupling as the key reactions. Further synthetic and biological investigations of such analogues are expected to lead to the discovery and development of potential payloads for antibody-drug conjugates as targeted cancer therapies.

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Source
http://dx.doi.org/10.1021/acs.joc.8b02137DOI Listing

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