Evidence for aminoglycoside participation in thiol activation of neocarzinostatin chromophore. Synthesis and reactivity of the epoxy dienediyne core
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.
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.Attached Files
Supplemental Material - ja00029a046_si_001.pdf
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Additional details
- Eprint ID
- 88457
- DOI
- 10.1021/ja00029a046
- Resolver ID
- CaltechAUTHORS:20180801-113954345
- NIH
- David and Lucile Packard Foundation
- Sterling Drug Company
- Upjohn Company
- Sandoz Pharmaceuticals Corporation
- Pfizer Inc.
- Created
-
2018-08-01Created from EPrint's datestamp field
- Updated
-
2021-11-16Created from EPrint's last_modified field
- Other Numbering System Name
- Arnold and Mabel Beckman Laboratories of Chemical Synthesis
- Other Numbering System Identifier
- 8181