Streamlined Total Synthesis of Shishijimicin A and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues thereof and Practical Syntheses of PhthNSSMe and Related Sulfenylating Reagents

Shishijimicin A is a scarce marine natural product with highly potent cytotoxicities, making it a potential payload or a lead compound for designed antibody–drug conjugates. Herein, we describe an improved total synthesis of shishijimicin A and the design, synthesis, and biological evaluation of a s...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2018-09, Vol.140 (38), p.12120-12136
Main Authors: Nicolaou, K. C, Li, Ruofan, Lu, Zhaoyong, Pitsinos, Emmanuel N, Alemany, Lawrence B, Aujay, Monette, Lee, Christina, Sandoval, Joseph, Gavrilyuk, Julia
Format: Article
Language:English
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Summary:Shishijimicin A is a scarce marine natural product with highly potent cytotoxicities, making it a potential payload or a lead compound for designed antibody–drug conjugates. Herein, we describe an improved total synthesis of shishijimicin A and the design, synthesis, and biological evaluation of a series of analogues. Equipped with appropriate functionalities for linker attachment, a number of these analogues exhibited extremely potent cytotoxicities for the intended purposes. The synthetic strategies and tactics developed and employed in these studies included improved preparation of previously known and new sulfenylating reagents such as PhthNSSMe and related compounds.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.8b06955