Synthesis of t-butyloxy carbonyl protected cyclic amino acids and its application in peptides solid synthesis
10.13220/j.cnki.jipr.2014.02.018
- Author:
Yong-Tao MA
1
Author Information
1. Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences
- Publication Type:Journal Article
- Keywords:
Conformational constrained;
Cyclic amino acids;
Solid synthesis;
Stability
- From:
Journal of International Pharmaceutical Research
2014;41(2):227-230
- CountryChina
- Language:Chinese
-
Abstract:
Objective To synthesize the t-butyloxy carbonyl (Boc) protected cyclic amino acids Boc-Acc5-OH and Boc-Acc6-OH, and then use this type of conformational constrained amino acids in the solid synthesis of peptides in order to investigate their application in the solid synthesis and stability in strong acid environment. Methods With corresponding cyclic ketones reacting with KCN and ammonium salt, cyclic compounds with cyano group were obtained. Then cyclic amino acids were achieved through the acidic hydrolysis of the cyano group. By reacting with Boc2O in the weak base solution, we obtained the Boc protected cyclic amino acids which were characterized in term of relative molecular mass and structure using ESI-MS and 1H NMR. We used solid-phase synthesis, p-methylbenzhydrylamine resin, Boc and 9-fluorenylmethoxycarbonyl(Fmoc) synthesis strategy to prepare the peptides, and analyzed them by HPLC and ESI-MS. Results The cyclic amino acids were identified by 1H NMR and ESI-MS. Besides, we obtained two gonadotropin-releasing hormone analogues which were characterized by ESI-MS. The crude peptides had a relatively high purity by HPLC and were easy to purify. Conclusion The cyclic amino acids have a favorable condensation efficiency in the solid synthesis technology, moreover, they can keep stable in strong acid condition.
