The simplest way to prepare the tosylate salts of amino acid benzyl esters, whose enantiomers are very important synthetic intermediates, is treatment of amino acid with benzyl alcohol and p-toluenesulfonic acid in a refluxing water-azeotroping solvent (Fischer–Speier esterification). However, to this day, the literature proposes only hazardous solvents, such as benzene, carbon tetrachloride, and chloroform, which must be absolutely avoided, or solvents, such as toluene and benzyl alcohol, which cause racemization because of too high boiling water azeotropes. On the other hand, the alternative successful use of cyclohexane, which we have recently reported for several amino acid benzyl esters, is inapplicable or not very efficient for ‘problematic’ amino acid such as tryptophan, arginine, and methionine, for which, indeed, the simple Fischer–Speier esterification is not described or poorly exemplified in the literature. Therefore, more polar solvents, in particular the green ethers CPME, TAME, and Me-THF, were selected and first considered for the preparation of methionine benzyl ester, previously accomplished in cyclohexane with modest yield. After discarding CPME and TAME, because causing racemization and decomposing under acidic conditions, respectively, we focused on Me-THF. In this ether, the benzyl esters of Met, Arg, and Trp could be obtained in good yield and, as proved by chiral HPLC or H NMR analysis, enantiomerically pure. The procedure was successfully extended to proline benzyl ester, which could be prepared enantiomerically pure and in quantitative yield both in cyclohexane and in Me-THF, thus avoiding the recently reported use of carbon tetrachloride.
Preparation of enantiopure methionine, arginine, tryptophan, and proline benzyl esters in green ethers by Fischer–Speier reaction / C. Bolchi, F. Bavo, L. Regazzoni, M. Pallavicini. - In: AMINO ACIDS. - ISSN 0939-4451. - 50:9(2018), pp. 1261-1268.
|Titolo:||Preparation of enantiopure methionine, arginine, tryptophan, and proline benzyl esters in green ethers by Fischer–Speier reaction|
BOLCHI, CRISTIANO (Corresponding)
|Parole Chiave:||Amino acid benzyl ester; Chiral HPLC; CPME; Me-THF; Mosher’s acid; Racemization; TAME; Water azeotrope; Biochemistry; Clinical Biochemistry; Organic Chemistry|
|Settore Scientifico Disciplinare:||Settore CHIM/08 - Chimica Farmaceutica|
|Data di pubblicazione:||2018|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s00726-018-2599-2|
|Appare nelle tipologie:||01 - Articolo su periodico|