ORGN 640

Synthesis of L-aspartyl-a-aminocyclobutanecarboxylic acid methyl ester:

L-aspartyl-a-aminocyclobutanecarboxylic acid methyl ester is a peptide sweetener reported by Goodman's group. We tried to synthesize this dipeptide by a multi-component reaction, Ugi reaction from protected L-aspartic acid, cyclobutanone, 2,4-dimethoxy benzylamine and 1-isocyanocyclohexene.

1-Isocyanocyclohexene is the ‘convertible isocyanide' reported by Armstrong's group. It can be synthesized from cyclohexanone and formamide via two steps. The removal of 2, 4-dimethoxy benzyl group and methanolysis of the cyclohexeneamide to form the desired methyl ester 3 were accomplished in one step by TFA in dichloromethane and quenching by methanol and pyridine.

Piperidine and diethylamine in different solvent were tried to deprotect the Fmoc (9-Fluorenylmethyloxycarbonyl) and Fm ester (9-Fluorenylmethyl ester) protecting groups of the protected dipeptide 3. But the methoxy group of the methyl ester was also removed by the substitution of amine to form the amide. Other base source, such as solid support piperazine will be used to perform the deprotection