Recently, we introduced 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) as a new dehydrating condensing agent.1) Practical features of DMT-MM are as follows: 1) the reaction proceeds by a convenient one-step procedure in which DMT-MM is simply added to a mixture of acids and amines in a solvent; 2) no additives are required; 3) DMT-MM is a stable but not hygroscopic solid; 4) no irritating properties to the eye and nose, nor allergenic properties were observed in our laboratory; 5) the highly water-soluble co-products can be readily removed by washing with water; 6) DMT-MM can be prepared at a low cost from inexpensive cyanuric chloride. In addition, it is noteworthy that DMT-MM enables us to carry out the direct onepot condensation of carboxylic acids and amines in protic solvents like methanol, ethanol, 2-propanol, or water, as well as in a variety of aprotic organic solvents.
2)In order to evaluate the usefulness of DMT-MM in peptide synthesis, the degree of racemization with this reagent should be examined. We have already reported that no diastereomeric isomer resulting from racemization was detected in the coupling of tert-butoxycarbonyl (Boc)-L-Leu-OH and H-L-Phe-OMe with DMT-MM in both tetrahydrofuran (THF) and MeOH.2) Taddei and co-workers recently found that DMT-MM is a useful alternative to benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) with regard to reaction yields and the purity of products in solid phase peptide synthesis using N-Fmoc amino acids.3) In contrast to the coupling of amino acids with a urethane-type N-protecting group that are known to be almost free from racemization, the C-terminal amino acids of Nishi-ku, Kobe 651-2180, Japan. Received November 26, 2001 accepted January 7, 2002 Racemization of the C-terminal amino acid (Ala) has been studied in various solvents during coupling between 4-methoxybenzyloxycarbonyl (Z(OMe))-Gly-L-Ala-OH and phenylalanine benzyl ester (H-Phe-OBzl) with 4-(4,6-dimethoxy-1,3,5-thiazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). The reaction occurred without substantial racemization in AcOEt, tetrahydrofuran (THF), N,N-dimethylformamide (DMF), CH 3 CN, and 2-PrOH, while a slight racemization was observed in dimethyl sulfoxide (DMSO), EtOH, and MeOH. The extent of racemization may correlate with the polarity of the solvents.