Protection of histidine in peptide synthesis: A Reassessment of the trityl group

✍ Scribed by Peter Sieber; Bernhard Riniker

• Publisher: Elsevier Science
• Year: 1987
• Tongue: French
• Weight: 233 KB
• Volume: 28
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)96856-4

✦ Synopsis

The trltyl (Trt) group 1s ideally suited for the sjde-chain protection of His In peptide syntheses, in combination with 9-fluorenylmethyloxycarbonyl (Fmoc) In Na-and protecting groups cleavable by mild acidolysis in other poslt1ons of the peptide. 2,4,5-trlchlorophenyl (Tcp)-and pentafluorophenyl (Pfp)-esters of Fmoc-His(Trt)-OH and Trt-Hls(Trt)-OH are 1 activated, but stable compounds. i:'inrn_frt. No-Trt Is selectively removable in the presence The imldazole ring of Hjs has continually been the cause of problems in peptide syntheses. If left unprotected, Its partial acylatlon during peptide coupling reactlons, and subsequent transfer of the acyl residue to other nucleophillc sites of the peptide, are known to produce 1 various by-products . In addition, activated derivatives of His are especially prone to racemization, due to intramolecular base catalysis by the side-chain. Many djfferent Imldazole protecting groups are known, but so far none of these has proven to be without speciftc problems. Tos, Dnp and Boc, which are often used, are not completely stable towards nucleophlles. Trt-derivatives of His have been known for a long time 2. Although H-His(Trt)-OH and Trt-