Polymerization of L-Alanylglycine with Diphenylphosphoryl Azide

Abstract

ABSTRACT:The polymerization reactions of L-alanylglycine with diphenylphosphoryl azide (DPPA) were investigated under various reaction conditions. Dimethyl sulfoxide and triethylamine were found to be the most suitable solvent and base, respectively, for this polymerization reaction. A reaction time of two days at room temperature, employing 1.3 equivalent moles of DPPA and 2.6 equivalent moles of triethylamine corresponding to the amount of L-alanylglycine were considered to be the most appropriate reaction condition. In this case, poly(L-alanylglycine) which has the intrinsic viscosity of 0.16 in dichloroacetic acid at 25°C was obtained in 43% yield. Its infrared absorption spectrum and elemental analysis, and the amino acid analysis or the optical rotation for the acid hydrolysate indicated the high purity of poly(L-alanylglycine) obtained by this DPPA method.KEY WORDSDiphenylphosphoryl azide (DPPA) has been used as a convenient reagent for racemization-free peptide synthesis since it was synthesized by Shioiri eta!. in 1972. 1 It is non-explosive and stable enough to be stored for a long time without decomposition.Recently, we reported that this reagent can also be used successfully for the polymerization of amino acids or peptides. 2 A polypeptide can easily be prepared by just stirring the solution or suspension of amino acid or peptide in a suitable solvent with DPPA and a tertiary amine such as triethylamine. Poly(amino acid)s such as poly(glycine), poly(Lalanine), poly(L-leucine), poly(y-benzyl L-glutamate), poly(e-benzyloxycarbonyl-L-lysine), poly(f3-alanine) and poly(6-aminohexanoic acid) were prepared by this method. 2 Sequential polypeptides such as poly( -alanylglycyl-L-histidyl-[3-alanylglycine), and poly(f3-benzyl-L-aspartyl-f3-alanylglycyl-O-benzyl-L-seryl-f3-alanylglycyl-L-histidyl-f3-alanylglycine) were also synthesized successfully, as previously reported. 2 In particular, the polymerization of L-histidine-containing hexa-or nonapeptide gave a high-molecular-weight sequential polypeptide. Thus the DPPA method seems to have the possibility of becoming one of the very convenient and efficient methods for polypeptide synthesis, especially for the synthesis of sequential polypeptides, if the further exhaustive investigation is performed. In developing this method of polymerization, it would be very helpful to investigate in detail the relationship between the reaction conditions and results, using one kind of peptide as a representative.In the present study, the polymerization of Lalanylglycine was investigated in detail to find the most suitable reaction conditions for this peptide and, as a result, useful information by which this DPPA method could be used for the general synthesis of sequential polypeptides was obtained. The detailed s!udy on the composition or the purity of resultant poly(L-alanylglycine) are also reported. EXPERIMENTAL MeasurementsElemental analyses were carried out with a Yanagimoto CHN Corder, Model MT-2. Optical rotations were measured with a Yanagimoto 183

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