SU1728224A1 - Method of n-substituted @@@-aminoacid pentafluorophenyl ethers synthesis - Google Patents

Abstract

The invention relates to α-amino acid derivatives, in particular to the preparation of the petafluorophenyl esters of N-substituted α-amino acids of the general formula R-0-CeFs, where R is a) M- (tert-butyloxycarbonyl) -1 -anyl; b) N- (tert-butyloxycarbonyl O-alanyl; c) N - (benzyloxycarbonyl) -My- (tert-butyloxycarbonyl) -1 -lysyl; d) 3,1 1-bis- (tert-butyloxycarbonyl) -1-alanyl; e) M- (benzyloxycarbonyl) -alanyl; e) N- (tert-butyloxycarbonyl) prolyl; g) S-benzyl-M- (t-butyloxycarbonyl) -1-cisteyl; h) M- (tert-butyloxycarbonyl) -1-leucyl; i) M, 0-bis (tert-butyloxycarbonyl) tyrosyl; j) N2- (benzyloxycarbonyl) tryptophanyl; l) 5- (M-nitroguanidino) -2- (tert-butoxycarboxamido) -1 -pentanoyl or m) 1, M-bis (tert-butyloxycarbonyl) -h histidyl - intermediates for peptide synthesis. The goal is to simplify the process and expand the range of target esters. Synthesis of lead from the corresponding N-substituted "-amino acids, pentafluorophenol and di (tert-butyl) pyrocarb.onata in a tertiary amine medium in the presence of pyridine, triethylamine or M-methylmorpholine, followed by separation of the target product by treating the mixture to pH 3 , 0-4,0 with an aqueous solution H2S04. These conditions make it possible to obtain, along with the known, three new ethers: the gross formula; output, %; m.p. & C: b) CnHuFsNO; 90, 83-85; and) CasHaeFsNO; 95; 122-125; m) С22Н24Р5№Ое; 92; 83-88. In addition, reduced temperatures, evaporation operations, the use of the d-cyclohexylcarbodiimide allergen are avoided, and the toxicity of the waste is reduced. 1 tab. 1L With vj IhO SO | Yu Yu 1

Description

This invention relates to a process for the preparation of the pentafluorophenyl esters of M-substituted α-amino acids.

The aim of the invention is to simplify the process and expand the range of pentafluorophenyl esters of M-substituted α-amino acids.

Examples 1-12. To a solution of 20 mmol of N-substituted amino acid in 120 mmol of an organic base is added 20

mmol pentafluorophenol and 22 mmol di (tert-butyl) pyrocarbonate. After 18 hours, 70 ml of 1 mol / l sulfuric acid solution (to pH 3-4) is added with vigorous stirring to 70 ml of sulfuric acid solution cooled to 0-5 ° C. The precipitate is filtered off, washed thoroughly with water (5 x 30 ml), 5% NaOH3 solution (5 x 30 ml), water (5 x 30 ml) and dried over PaOs.

The yield of pentafluorophenyl ethers of N-substituted "-amino acids 86-98%.

The table lists the specific conditions for the preparation of the pentafluorophenyl esters of N-substituted α-amino acids and their certain physicochemical properties.

The technical and economic efficiency of the proposed method consists in simplifying the process, which is expressed in eliminating the need for lowering the temperature during the process, eliminating the operation of evaporation of the solution of the target products under reduced pressure, eliminating the strong allergen (dicyclohexylcarbodiimide) from the process and reducing the toxicity of the waste. The method allows to obtain previously unknown pentafluorophenyl esters of M- (tert-butyloxycarbonyl) -0-alanine, M, 0-bis (tert-butyloxycarbonyl) -1-tyrosine and 1, N-bis- (tert-butyloxycarbonyl) -1 -histidine.

Claims (1)

Invention Formula 0 five The method of obtaining pentafluorophenyl esters of N-substituted "-amino acids, including the interaction of the corresponding N-protected amino acid with pentafluorophenol in the presence of a condensing agent in an organic solvent, followed by separation of the target product, characterized in that, in order to simplify the process and expand the range of target products, as Di (t-butyl) pyrocarbonate is used as a condensing agent, the process is carried out in a tertiary amine medium, and the target products are isolated by precipitation by treatment with p the reaction mixture to pH 3.0-4.0 with an aqueous solution of sulfuric acid.