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Practical Synthesis of (20 S)-10-(3-Aminopropyloxy)-7-ethylcamptothecin, a Water-Soluble Analogue of Camptothecin.

Authors :
Watanabe, Tatsuya
Tsuboi, Yasunori
Nomura, Sumihiro
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