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Practical Synthesis of (20 S)-10-(3-Aminopropyloxy)-7-ethylcamptothecin, a Water-Soluble Analogue of Camptothecin.
- Source :
- Chemistry - An Asian Journal; Mar2013, Vol. 8 Issue 3, p630-638, 9p
- Publication Year :
- 2013
-
Abstract
- A robust, practical synthesis of (20 S)-10-(3-aminopropyloxy)-7-ethylcamptothecin (T-2513, 5), which is a water-soluble analogue of camptothecin, has been developed. The key step in this synthesis is a highly diastereoselective ethylation at the C20 position by using N-arylsulfonyl-( R)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid ester as a chiral auxiliary, which affords the key intermediate ethyl-( S)-2-acyloxy-2-(6-cyano-5-oxo-1,2,3,5-tetrahydroindolizin-7-yl)butanoate ( 8k) in 93 % yield and 87 % de. Optically pure compound 8k was obtained by a single recrystallization from acetone and its further elaboration through Friedlander condensation afforded compound 5. This synthesis does not require any chromatographic purification steps and can provide compound 5 on a multi-gram scale in 6.3 % overall yield (16 steps). [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 18614728
- Volume :
- 8
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Chemistry - An Asian Journal
- Publication Type :
- Academic Journal
- Accession number :
- 85674811
- Full Text :
- https://doi.org/10.1002/asia.201200904