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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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
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cited_by cdi_FETCH-LOGICAL-a324t-25698043372446d90b408a60a05af77cb9a44b06af9bdffe5f731ba3882e1c4f3
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container_end_page 12136
container_issue 38
container_start_page 12120
container_title Journal of the American Chemical Society
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creator Nicolaou, K. C
Li, Ruofan
Lu, Zhaoyong
Pitsinos, Emmanuel N
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Lee, Christina
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Gavrilyuk, Julia
description 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.
doi_str_mv 10.1021/jacs.8b06955
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title 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
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