✦ LIBER ✦
Synthetic Studies on Camptothecins. Part 3 : Total Synthesis of (20S)-7-Ethyl-10-hydroxycamptothecin via a Bifunctional Thiourea-Based Cinchona Alkaloid-Mediated Enantioselective Cyanosilylation Strategy
✍ Scribed by Yun-Yan Kuang; Jing-Ze Niu; Fen-Er Chen
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- German
- Weight
- 185 KB
- Volume
- 93
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
A concise and efficient asymmetric process for the total synthesis of (20__S__)‐7‐ethyl‐10‐hydroxycamptothecin (=SN‐38; 1f), an active metabolic form of the prodrug irinotecan, is described. This approach features the enantioselective cyanosilylation of indolizinone 4 into the corresponding cyanohydrin 5, mediated by a bifunctional thiourea‐based cinchona alkaloid under mild conditions, and I~2~‐catalyzed Friedländer condensation of the tricyclic lactone 6 and 2‐amino‐5‐hydroxy propiophenone (=1‐(2‐amino‐5‐hydroxyphenyl)propan‐1‐one).