Probing the SAR of dEpoB via chemical synthesis: A total synthesis evaluation of C26-(1,3-dioxolanyl)-12,13-desoxyepothilone B Journal Article
| Authors: | Chappell, M. D.; Harris, C. R.; Kuduk, S. D.; Balog, A.; Wu, Z.; Zhang, F.; Lee, C. B.; Stachel, S. J.; Danishefsky, S. J.; Chou, T. C.; Guan, Y. |
| Article Title: | Probing the SAR of dEpoB via chemical synthesis: A total synthesis evaluation of C26-(1,3-dioxolanyl)-12,13-desoxyepothilone B |
| Abstract: | A practical total synthesis of 26-(1,3-dioxolanyl)-12,13-desoxyepothilone B (26-dioxolanyl dEpoB) was accomplished in a highly convergent manner. A novel sequence was developed to produce the vinyl iodide segment 17 in high enantiomeric excess, which was used in a key B-alkyl Suzuki merger. Subsequently, a Yamaguchi macrocyclization formed the core lactone, while a selective oxidation and a late stage Noyori acetalization incorporated the dioxolane functionality. Sufficient amounts of synthetic 26-dioxolane dEpoB were produced using this sequence for an in vivo analysis in mice containing xenograft CCRF-CEM tumors. |
| Keywords: | controlled study; unclassified drug; nonhuman; neoplasms; mouse; animals; mice; animal model; antineoplastic activity; drug structure; xenograft model antitumor assays; drug synthesis; structure-activity relationship; mice, nude; tumors; disease progression; molecular structure; cyclization; structure analysis; inhibitory concentration 50; oxidation; synthesis (chemical); stereochemistry; epothilones; epothilone b; iodine; epoxy compounds; isomers; grafts; aromatic compounds; cancer; article; yamaguchi macrocyclizations; 26 (1,3 dioxolanyl) 12,13 desoxyepothilone b |
| Journal Title: | Journal of Organic Chemistry |
| Volume: | 67 |
| Issue: | 22 |
| ISSN: | 0022-3263 |
| Publisher: | American Chemical Society |
| Date Published: | 2002-11-01 |
| Start Page: | 7730 |
| End Page: | 7736 |
| Language: | English |
| DOI: | 10.1021/jo020180q |
| PUBMED: | 12398496 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
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