68739-90-2Relevant academic research and scientific papers
Preparation of enantiopure methionine, arginine, tryptophan, and proline benzyl esters in green ethers by Fischer–Speier reaction
Bolchi, Cristiano,Bavo, Francesco,Regazzoni, Luca,Pallavicini, Marco
, p. 1261 - 1268 (2018/06/11)
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.
One-step preparation of enantiopure l- or d-amino acid benzyl esters avoiding the use of banned solvents
Bolchi, Cristiano,Bavo, Francesco,Pallavicini, Marco
, p. 965 - 974 (2017/04/11)
The enantiomers of amino acid benzyl esters are very important synthetic intermediates. Many of them are currently prepared by treatment with benzyl alcohol and p-toluenesulfonic acid in refluxing benzene or carbon tetrachloride, to azeotropically remove water, and then precipitated as tosylate salt by adding diethyl ether. Here, we report a very efficient preparation of eight l- or d-amino acid benzyl esters (Ala, Phe, Tyr, Phg, Val, Leu, Lys, Ser), in which these highly hazardous solvents are dismissed using cyclohexane as a water azeotroping solvent and ethyl acetate to precipitate the tosylate salt. With some work-up modifications and lower yield, the procedure can be applied also to methionine. Chiral HPLC analysis shows that all the benzyl esters, including the highly racemizable ones such as those of phenylglycine, tyrosine and methionine, are formed enantiomerically pure under these new reaction conditions thus validating the solvents replacement. Contrariwise, toluene cannot be used in place of benzene or carbon tetrachloride because leading to partially or totally racemized amino acid benzyl esters depending on the polar effect of the amino acid α-side chain as expressed by Taft’s substituent constant (σ*).
Synthesis of Met-enkephalin by solution-phase peptide synthesis methodology utilizing para-toluene sulfonic acid as N-terminal masking of l-methionine amino acid
Khan, Riaz A.
, p. 884 - 888 (2016/11/11)
The Met-enkephalin, Tyr-Gly-Gly-Phe-Met, was synthesized by the solution-phase synthesis (SPS) methodology employing -OBzl group as carboxyls' protection, while the t-Boc groups were employed for the N-terminal α-amines' protection for the majority of the amino acids of the pentapeptide sequence. The l-methionine (l-Met) amino acid was used as PTSA.Met-OBzl obtained from the simultaneous protection of the α-amino, and carboxyl group with para-toluene sulfonic acid (PTSA) and as-OBzl ester, respectively in a C-terminal start of the 2?+?2?+?1 fragments condensation convergent synthetic approach. The protection strategy provided a short, single-step, simultaneous, orthogonal, nearly quantitative, robust, and stable process to carry through the protected l-methionine and l-phenylalanine coupling without any structural deformities during coupling and workups. The structurally confirmed final pentapeptide product was feasibly obtained in good yields through the current approach.
A One-Pot Synthesis of Symmetrical and Unsymmetrical Dipeptide Ureas
Fayad, Antoine Abou,Pubill-Ulldemolins, Cristina,Sharma, Sunil V.,Day, David,Goss, Rebecca J. M.
, p. 5603 - 5609 (2015/09/01)
We describe a flexible and high yielding synthesis of 1,3-disubstituted ureas that allows for the construction of both symmetrical and unsymmetrical dipeptide ureas, including easy access to 13C-labelled ureas, from amino acids and carbon dioxide at atmospheric pressure. We describe a flexible and high yielding synthesis of 1,3-disubstituted ureas, that allows for the construction of both symmetrical and unsymmetrical dipeptide ureas, including easy access to 13C labelled ureas, from amino acids and carbon dioxide at atmospheric pressure.
TRANSFORMATION OF GLYCYRRHIZIC ACID IV. SYNTHESIS OF TRITERPENE GLYCOPEPTIDES
Baltina, L. A.,Ryzhova, S. A.,Vasil'eva, E. V.,Tolstikov, G. A.
, p. 40 - 46 (2007/10/02)
The synthesis has been carried out of new triterpene glycopeptides, derivatives of β-glycyrrhizic acid, using benzyl (or 4-nitrobenzyl) esters of L-amino acids.Activation of the carboxyl groups of the glycoside was effected using N-hydroxy-benzotriazole-N,N'-dicyclohexylcarbodiimide.Deblocking of the compounds obtained was carried out by catalytic hydrogenolysis over Pd/C.Keywords: β-glycyrrhizic acid, glycopeptides
