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Evidence for aminoglycoside participation in thiol activation of neocarzinostatin chromophore. Synthesis and reactivity of the epoxy dienediyne core

Myers, Andrew G. and Harrington, Philip M. and Kwon, Byoung-Mog (1992) Evidence for aminoglycoside participation in thiol activation of neocarzinostatin chromophore. Synthesis and reactivity of the epoxy dienediyne core. Journal of the American Chemical Society, 114 (3). pp. 1086-1087. ISSN 0002-7863. doi:10.1021/ja00029a046. https://resolver.caltech.edu/CaltechAUTHORS:20180801-113954345

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Abstract

The reaction of the chromophore subunit (1) of the natural antitumor antibiotic neocarzinostatin with methyl thioglycolate produces an NMR-observable intermediate, assigned as 2, which decays with a half-life of ~2 h at -38 °C to form the putative biradical 3. While the latter rearrangement is striking, perhaps no less so is the thiol addition step (1 → 2), which occurs readily at -70 °C in acetic acid-tetrahydrofuran (1:9, t_(1/2) ≃ 1.5 h, 0.2 M thiol). Reported herein are (1) the assembly of the full core functionality of neocarzinostatin chromophore in a synthetic system and (2) the preparation of a nonbasic derivative of the chromo-phore itself. Experiments with these synthetic materials provide strong evidence that thiol activation of 1 is facilitated dramatically through participation of the carbohydrate amino group as an internal base.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1021/ja00029a046DOIArticle
https://pubs.acs.org/doi/suppl/10.1021/ja00029a046PublisherSupporting Information
Additional Information:© 1992 American Chemical Society. Received October 17, 1991. Generous support from the National Institutes of Health, the David and Lucile Packard Foundation, the Sterling Drug Company, the Upjohn Company, Sandoz Pharmaceuticals Corporation, and Pfizer Inc. is gratefully acknowledged. We are indebted to Kayaku Co., Ltd. for neocarzinostatin powder.
Funders:
Funding AgencyGrant Number
NIHUNSPECIFIED
David and Lucile Packard FoundationUNSPECIFIED
Sterling Drug CompanyUNSPECIFIED
Upjohn CompanyUNSPECIFIED
Sandoz Pharmaceuticals CorporationUNSPECIFIED
Pfizer Inc.UNSPECIFIED
Other Numbering System:
Other Numbering System NameOther Numbering System ID
Arnold and Mabel Beckman Laboratories of Chemical Synthesis8181
Issue or Number:3
DOI:10.1021/ja00029a046
Record Number:CaltechAUTHORS:20180801-113954345
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20180801-113954345
Official Citation:Evidence for aminoglycoside participation in thiol activation of neocarzinostatin chromophore. Synthesis and reactivity of the epoxy dienediyne core. Andrew G. Myers, Philip M. Harrington, and Byoung Mog Kwon. Journal of the American Chemical Society 1992 114 (3), 1086-1087. DOI: 10.1021/ja00029a046
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:88457
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:01 Aug 2018 18:57
Last Modified:16 Nov 2021 00:27

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