Synthesis of Novel N9-Substituted Purine Derivatives from Polymer Supported 伪-Amino Acids
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- 作者：David Vanda ; Radek Jorda ; Barbora Lemrov谩 ; Tereza Voln谩 ; Vladim铆r Kry拧tof ; Claire McMaster ; Miroslav Soural
- 刊名：ACS Combinatorial Science
- 出版年：2015
- 出版时间：July 13, 2015
- 年：2015
- 卷：17
- 期：7
- 页码：426-432
- 全文大小：458K
- ISSN：2156-8944
文摘
Solid-phase synthesis of purine derivatives bearing an 伪-amino acid motif in position 9 is described herein. Polymer supported amines were acylated with various Fmoc-伪-amino acids and, after cleavage of the protecting group, arylation with 4,6-dichloro-5-nitropyrimidine or 2,4-dichloro-5-nitropyrimidine was performed. The second chlorine atom was replaced with various amines. Subsequent reduction of the nitro group, followed by reaction with aldehydes, afforded the purine scaffold. After cleavage from the polymer support, the target compounds were obtained in very good crude purity, good overall yields, and excellent enantiomeric purity. The anticancer activity of prepared compounds was tested in vitro against human cancer cell lines MCF7 and K562, and they were found to have mild, but clear dose-dependent effects.