Synthesis of p-nitrobenzyloxycarbonbyl-l-phenylalanyln-n-carbobenzoxy-l-histidyl-l-leucine methyl ester as an intermediate for the synthesis of a fluorogenic substrate for angiotensin-converting enzyme

• Main Author: Wilson, Richard Larry
• Format: Others
• Published: DigitalCommons@Robert W. Woodruff Library, Atlanta University Center 1979
• Subjects: Chemistry
• Online Access: http://digitalcommons.auctr.edu/dissertations/1287; http://digitalcommons.auctr.edu/cgi/viewcontent.cgi?article=2355&context=dissertations

The attempted synthesis of p-nitrobenzyloxycarbonyl-Lphenylalanyl-N-carbobenzoxy--L-histidyl-L- leucine methyl ester,an intermediate in the synthesis of p-nitrobenzyloxycarbonyl-Lphenylalanyl-N-carbobenzoxy-L-histidyl-L-leucine_4_hydroxy3-methoxybenzyl ester is described. This tripeptide intermediatewill be important in the development of a tripeptide fluorogenicsubstrate for angiotensin-converting enzyme because of its fluorescent probe.Analyses indicate that L-phenylalanyl-N-carbobenzoxy-Lhistidyl-L-leucine methyl ester hydrochloride tetrahydrate wasobtained as a result of cleavage of the p-nitrobenzyloxycarhonylgroup from p-nitrobenzyloxycarbonyl-L-phenylalanyl-N-carbohenzoxyL-histidyl-L-leucinemethyl ester.We attempted to prepare the tripeptide intermediate by theuse of the stepwise approach starting from the carboxyl terminalend and adding one N-protected acid after the other. DicarbobenzoxyL—histidine and L-leucine methyl ester were coupled by the dicyclo—hexylcarbodiimide method to form dicarbobenzoxy-L-histidyl-Lleucine methyl ester. The latter was treated with hydrobromic acidin dioxane and the crude dihydrobromide, after neutralization, wasreacted with p-nitrobenzyloxycarbonyl-L-phenylalanjne to formp_nitrobenzyloxycarbonyl-L-phenylalany1-N-carbobenzoxy-L-histidy1-L-leucine methyl ester.