Patent ID: 6967202

Claim:
A method of synthesizing a diketopiperazines of the following formula: wherein: R 1 is —CH 2 COR 3 , or —CH 2 CH 2 COR 3 ; R 2 is the side chain of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, phenylalanine, tyrosine, tryptophan, thyroxine, cysteine, methionine, norvaline and ornithine; R 3 is —OH, —NH 2 , —OR 4 , —NHR 4 , or —NR 4 R 4 ; and each R 4 is independently an alkyl, aryl, alkylaryl, or arylalkyl, the method comprising: (a) reacting a first amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, phenylalanine, tyrosine, tryptophan, thyroxine, cysteine, methionine, norvaline and ornithine, with a second amino acid derivative having one of the following formulas: NH 2 CH(CH 2 COOR 5 )COOH or NH 2 CH(CH 2 CH 2 COOR 5 )COOH, wherein R5 is benzyl, under conditions effective to form a dipeptide; and, (b) cyclizing the dipeptide at a temperature of between 80° C. and 180° C. in a neutral solvent to form a diketopiperazine having the formula; wherein: R 6 is —CH 2 COOR 5 , or —CH 2 CH 2 COOR 5 ; and (c) hydrogenating the diketopiperazine to remove the R 5 group and form a diketopiperazine having the formula: wherein: R 1 is —CH 2 COOH, or —CH 2 CH 2 COOH; and, R 2 is the side chain of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, serine, threonine, aspartic acid, asparagine, glutamic acid, glutamine, lysine, hydroxylysine, histidine, arginine, phenylalanine, tyrosine, tryptophan, thyroxine, cysteine, methionine, norvaline and ornithine.