- THE TRANSFORMYLATION REACTION - TRANSFER OF AN N-FORMYL RESIDUE IN AMINO ACID AND PEPTIDE DERIVATIVES TO NUCLEOPHILIC GROUPS - AS A SIDE REACTION OF PEPTIDE SYNTHESIS
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In the course of a study of the enzymatic synthesis of peptides from N-formylamino acids, the transfer of a formyl group to nucleophilic acceptors present in the aqueous-organic reaction medium - amino acid esters, peptides, and aromatic amines - has been detected, and this to the greater degree the higher the nucleophilicity of the acceptor.The transfer of a formyl group from a number of formylamino acids and formylpeptides to phenylalanine methyl ester has been studied.A fall in the yield of the transformylation reaction on passing from formyl derivatives with a free carboxy group to formyl peptides or esterified formylamino acids has been found.No transfer of an acetyl group was observed under these conditions.On the use of formyl derivatives in peptide synthesis the possibility of the occurrence of the transformylation reaction and the resulting appearance of by-products must be taken into account.Key words: peptide; enzymatic synthesis; transformylation.
- Kotlova, E. K.,Levin, E. D.,Yusupova, M. P.,Rozynov, B. V.,Stepanov, V. M.
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p. 678 - 686
(2007/10/02)
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- Preparation of N-protected α-L-aspartyl-L-phenylalanine methyl ester
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Disclosed is an improved process for the preparation of an N-protected α-L-aspartyl-L-phenylalanine methyl ester from an N-protected L-aspartic anhydride and L-phenylalanine methyl ester, the improvement which comprises employing the L-phenylalanine methyl ester in the form of a mineral acid salt thereof and conducting the reaction either (a) in an organic solvent and in the presence of a salt of an organic carboxylic acid, or (b) in an organic solvent comprising an organic carboxylic acid and in the presence of at least one member of the group consisting of an alkali metal or an alkaline earth metal inorganic base, an ammonium alkali metal or alkaline earth metal salt of an organic carboxylic acid and ammonium carbonate. The starting N-protected aspartic anhydride, e.g., N-benzyloxycarbonyl-L-aspartic anhydride, can be produced by the reaction of N-protected aspartic acid with phosgene. When the N-protecting group sibenzyloxycarbonyl and the solvent is acetic acid, the desired product can be isolated from the reaction mixture in crystalline form in high purity by adding water thereto.
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- Process for preparing α-L-aspartyl-L-phenylalanine methyl ester
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A process for preparing α-L-aspartyl-L-phenylalanine methyl ester: STR1 in which: (a) the compound methyl N(α-L-aspartyl)α-aminocinnamate, protected at the nitrogen, of formula: STR2 where R is a protector group at the nitrogen, is subjected to hydrogenation at the olefin bond by means of gaseous hydrogen in the presence of a hydrogenation catalyst, to give the compound of formula: STR3 where R has the aforesaid meaning, in the form of a mixture of α-L-aspartyl-L-phenylalanine methyl ester protected at the nitrogen, and α-L-aspartyl-D-phenylalanine methyl ester protected at the nitrogen; (b) the protector group is removed from the α-L-aspartyl-L-phenylalanine and α-L-aspartyl-D-phenylalanine methyl esters protected at the nitrogen; (c) the α-L-aspartyl-L-phenylalanine methyl ester is separated and recovered from the deprotection reaction product.
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- Method of removing formyl groups from N-formyl-amino acid and N-formyl-peptide esters having free carboxyl groups
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The masking N-formyl group of an N-formyl-amino acid ester or an N-formyl-peptide ester having a free carboxyl group is removed without major side reactions when the ester is contacted with a strong acid in a mixture of water and a specific organic solvent such as methyl ethyl ketone or acetonitrile. This method is specifically applicable to the production of L-aspartyl amino acid lower alkyl esters which are known as low calorie sweeteners.
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