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Updated: Jul 1, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Synthesis of a Non-Symmetrical Disorazole C1-Analogue and Its Biological Activity
Luca Lizzadro1, Oliver Spieß2, Silke Reinecke3
1Medicinal Chemistry and Chemical Biology Laboratory, School of Pharmacy, University of California San Francisco, 600 16th St., San Francisco, CA 94158, USA.
Abstract:
The synthesis of a novel disorazole C1 analogue is described, and its biological activity as a cytotoxic compound is reported. Based on our convergent and flexible route to the disorazole core, we wish to report a robust strategy to synthesize a non-symmetrical disorazole in which we couple one half of the molecule containing the naturally occurring oxazole heterocycle and the second half of the disorazole macrocycle containing a thiazole heterocycle. This resulted in a very unusual non-symmetrical disorazole C1 analogue containing two different heterocycles, and its biological activity was studied. This provided exciting information about SAR (structure-activity-relationship) for this highly potent class of antitumor compounds.
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