Method for synthesizing N-fluorene methoxycarbonyl-N-trityl-D-glutamine

Abstract

The invention relates to a synthetic method of N-fluorenylmethoxycarbonyl-N- triphenylmethyl-D-glutamine to solve the current problems of the shortage of D-Gln raw materials and high cost of synthesizing products from the D-Gln. The synthesis includes the following steps: a. D-glutamate and a carbobenzoxy chloride are reacted to get the N-carbobenzoxy-D-glutamate; in an organic solvent N and N-dimethylformamide with the existence of a triethylamine and bromomethyl-benzene, the N-carbobenzoxy-D-glutamate selectively protects an Alpha-carboxyl to get an N-benzyloxycarbonyl-D-benzyl L-glutamate; b. the triethylamine, ethyl chloroformate and ammonia are added to N- benzyloxycarbonyl-D- benzyl L-glutamate organic solvent with a molar ratio of 1:1:2 to 6; after reacted for 6 to 24 hours under a temperature of -20 to 20 DEG C, an N- benzyloxycarbonyl-D-glutaminebenzylester is gotten; c. the product of b, acetate liquor is reacted with a triphenylmethanol under a catalysis of concentrated sulfuric acid, and N- benzyloxycarbonyl-N-triphenylmethyl-D-glutaminebenzylester can be gotten after reacted for 8 to 24 hours under a temperature of 40 to 60 DEG C; d. benzyloxycarbonyl and benzyl are detracted from the product of c to get the N-triphenylmethyl-D-glutamine; e. the product of d is protected by an Fmoc group to get the N-fluorenylmethoxycarbonyl-N-triphenylmethyl-D- glutamine.

Description

Technical field:

[0001] The invention relates to a synthesis method of N-fluorenylmethoxycarbonyl-N-trityl-D-glutamine (Fmoc-D-Gln(Trt)-OH). Background technique:

[0002] N-fluorenylmethoxycarbonyl-N-trityl-D-glutamine is a commonly used reagent in solid-phase peptide grafting, and we can synthesize it using D-glutamine as a starting material by a relatively simple method (ref: Tetrahedron Lett; EN; 32; 6; 1991; 739-742), that is, Z-D-Gln-OH obtains the product through a three-step reaction, but due to the relatively low yield and the high market price of D-Gln raw materials, the price of D-Glu is It is relatively cheap, so we developed this synthesis method from this perspective. The structural formula of Fmoc-Gln (Trt)-OH is:

[0003] Invention content:

[0004] The purpose of the present invention is to provide a synthetic method of N-fluorenylmethoxycarbonyl-N-trityl-D-glutamine. The method solves the problem of high synthesis cost of D-glutamine at present. Th...

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