The total synthesis of dynemicin A leading to development of a fully contained bioreductively activated enediyne prodrug Journal Article
| Authors: | Shair, M. D.; Yoon, T. Y.; Mosny, K. K.; Chou, T. C.; Danishefsky, S. J. |
| Article Title: | The total synthesis of dynemicin A leading to development of a fully contained bioreductively activated enediyne prodrug |
| Abstract: | The title compound has been synthesized as its racemate in 33 steps. An intramolecular Diels-Alder reaction (24 → 25) was used to provide control over the eventual cis C4-C7 relationship. The installation of another cis related ethynyl group at C2 arose from transformation 40 → 42 whose directionality is governed by a benzophenone ketal functioning as a temporary steric control unit. Closure of the enediyne unit was accomplished on a trimethylsilylethoxycarbonyl (TEOC) protected dihydroquinoline derivative. It involved use of a novel bis-iodoalkyne/distannylethylene interpolative coupling transformation (61 + 58 → 63). In the terminal phase of the synthesis, a novel iminoquinone ketal 74 was condensed with homophthalic anhydride derivative 78 as indicated. The final deprotection involved cleavage of a methoxymethyl ester and two methoxymethyl phenol ethers. From this work, there arose the concept and demonstration of p-quinone monoimines 82 and 93, as bioreductively activated enediyne prodrugs. |
| Keywords: | controlled study; human cell; nonhuman; adenocarcinoma; animal cell; mouse; animal model; cytotoxicity; in vitro study; drug synthesis; tumor cell; mitomycin c; antineoplastic antibiotic; technique; reaction analysis; dna cleavage; human; article; dynemicin a |
| Journal Title: | Journal of the American Chemical Society |
| Volume: | 118 |
| Issue: | 40 |
| ISSN: | 0002-7863 |
| Publisher: | American Chemical Society |
| Date Published: | 1996-10-09 |
| Start Page: | 9509 |
| End Page: | 9525 |
| Language: | English |
| DOI: | 10.1021/ja960040w |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 22 November 2017 -- Source: Scopus |
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