The dynamic kinetic resolution in the synthesis of alkyl N acetylphenylalanyl (S) valinates was studied by the mixed anhydride method. The structure of the ester group of the amino component appeared to exert no substantial effect on the diastereoselectivity of the reaction.The dynamic kinetic resolution (DKR) method has attracted increasing attention of researchers in the recent time. The in situ epimerization of a chiral substrate occurs during this method, which makes it possible to perform syntheses with high diastereoselectivity. 1-6 5(4H ) Oxazo lones are very convenient substrates in DKR processes, because they are rapidly racemized and react readily with nucleophiles. They are widely used for syntheses of modi fied α amino acids and their derivatives. 7-10The synthesis of peptides by the mixed anhydride method is accompanied (under certain conditions) by substantial racemization, which proceeds mainly through the formation of 5(4H ) oxazolones. 11 The reaction of the latter with esters of amino acids affords a diastereomeric mixture of peptides. Diastereoselectivity in this process takes place when, along with the fast racemization of intermediate 5(4H ) oxazolone, one of its stereoisomers reacts with the amino component more rapidly than an other. 7 Therefore, the formation of dipeptide is the DKR process. The determination of factors favoring an increase in differences in the rates of interaction of oxazolone stereoisomers with the amino component provides a pos sibility of diastereoselective synthesis of dipeptides.In the previous work 12 we studied the influence of the nature of the side chain of the amino component on the diastereoselectivity of syntheses of dipeptides of N acetyl (S) phenylalanine (1). It is found that the introduction of 20% excess triethylamine provides the fast racemization of intermediate 5(4H ) oxazolone. The (R) isomer of 5(4H ) oxazolone 2″ reacts more rapidly with ethyl esters of (S) amino acids (Ala, Phe, Val, Glu), which results in the predominant formation of (R,S) diastereomers, whose content in the mixture is 61-90%. The main product of this DKR is dipeptide with the (R) phenylalanine residue.The purpose of the present work is to study the influ ence of the R substituent in the ester group of the amino component on the diastereoselectivity of condensation of alkyl (S) valinates with N acetyl (S) phenylalanine (1) (Scheme 1). (3, 7), Et (4, 8), Bu t (5, 9), Bn (6, 10)
Scheme 1
R = Me
Peptides U 0400 Study of the Influence of the Alkyl Ester Group in (S)-Valinates on Diastereoselectivity of Their Condensation with N-Acetylphenylalanine by the Mixed AnhydrideMethod. -(ZHDANOVA, E. A.; SOLIEVA, N. Z.; SADRETDINOVA, L. S.; EZHIKOVA, M. A.; KODESS, M. I.; KRASNOV*, V. P.; Russ. Chem. Bull. 55 (2006) 5, 925-927; Postovsky Inst. Org. Synth., Russ. Acad. Sci., Ekaterinburg 620219, Russia; Eng.) -H. Toeppel 06-178
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