Welcome to Suzhou Tianma Pharma Group Tianji Bio-pharmaceutical Co.
Contact Us
TEL: +86-512-68322275
FAX:
MOBILE: +86-18315825527
HTTP: www.tianjibio.com/
ADDRESS: Suzhou, Mudu Town ,Road East Huayuan 199
EMAIL: peptide@tianmapharma.com
QQ: message
Skype:
Your Location:Home > News > Details

News

A Reinvestigation of the Mixed Carbonic Anhydride Method of Peptide Synthesis

AddTime:2019-09-17

Factors influencing the reaction yields and formation of the side products during coupling of N-carbobenzoxyamino acids with dialkyl or diphenyl aminoalkylphosphonates, by means of mixed anhydride procedure, were evaluated. The recommended procedure, arising from these studies, involves the use of chloroform/ethyl chloroformate/triethylamine system and delicate warming of the reaction mixture during the coupling step.
Factors influencing the reaction yields and formation of the side products during mixed 

The factors which affect yield and racemization in custom peptide synthesis by the mixed carbonic anhydride method have been investigated. Good results in test cases were obtained when the tertiary amine necessary for formation of the mixed anhydride contained at least one N-methyl group, and it was not used in excess, indicating the importance of steric factors. Reduction of "basicity" of the amine was found to be favorable; complete racemization was found with an excess of trimethylamine as the tertiary base, and none with an excess of N-methyl-morpholine in the test Z-Gly-Phe-Gly-OEt synthesis in ethyl acetate or tetrahydrofuran. 

The more sensitive Bz-Leu-Gly-OEt synthesis gave no racemate with 1 equiv of N-methylmorpholine but some racemate with 2 equiv. The effects on racemization of change of solvent, temperature, time allowed for mixed anhydride formation, and several anions are reported. Evidence for racemization via oxazolones is given. Best yields were obtained with isobutyl chloroformate as the reagent. The principles disclosed here should be useful in improving other acylations.

custom peptide synthesis
Copyright 2014-2019. All rights reserved. Suzhou Tianma Pharma Group Tianji Bio-pharmaceutical Co.