Tert-butyl. Benzyloxy Carbonyl Asparagine Fmoc Tyrosine Benzyl Ether Synthesis

For the purpose of developing simple and effective protection routes of L-asparagine and L-tyrosine, the synthesis of Z-Asn-OBut and N-Fluorenylmethoxycarbonyl-O-benzyltyosine (Fmoc-Tyr(Bzl)-OH) were studied. The amino group of asparagine was protected by Z group with benzyl chloroformate. The Z-Asn-OH obtained was then treated with t-butyl acetate to give Z-Asn-OBut via transesterification. The reaction parameters such as reaction temperature, reaction time and catalyst dosage were optimized and 95% of Z-Asn-OBut were obtained. Reaction of L-tyrosine with benzyl bromide in the presence of copper sulfate led to the protection of phenol group on the side chain of L-tyrosine to give H-Tyr(Bzl)-OH in 45% yield via a copper complex intermediate. The formation of copper complex intermediate protected the carboxyl group of L-tyrosine effectively and led the benzylation take place on the side chain of L-tyrosine. The copper complex intermediate was isolated and proved to be a four coordinated complex by IR and elemental analysis. H-Tyr(Bzl)-OH was then react with fluorenylmethyl chloroformate in dioxane or THF to give N-Fluorenylmethoxycarbonyl-O-benzyltyosine (Fmoc-Tyr(Bzl)-OH) in 98% yield.