New mild acid-labile protecting groups for the guanidino function of N alpha-fluorenylmethoxycarbonyl-L-arginine in solid-phase peptide synthesis: 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-yl, 2-methoxy-10,11-dihydoro-5H-dibenzo[a,d]cyclohepten-5-yl and 5H-dibenzo[a,d]cyclohepten-5-yl groups.
10,11-Dihydro-5H-dibenzo[a,d]cyclohepten-5-yl [5-dibenzosuberyl] and 5H-dibenzo[a,d]-cyclohepten-5-yl [5-dibenzosuberenyl] groups have been found to be useful protecting groups for the guanidino function of arginine in solid-phase peptide synthesis on Fmoc chemistry. The arginine derivatives (4a,b,c) derivatized with these groups were easily deprotected with mild acid (less than 30 min with 25% trifluoroacetic acid). Tryptophan-containing peptide sequences, two hexapeptides (6) and (8), were synthesized in good yield by mild acid treatment (50% trifluoroacetic acid in 1 h) of the peptide resins (5a,c-f and 7a,c,d) assembled via 4a,b,c using benzotriazol-1-yl-oxy-tris-(pyrrolidino)-phosphonium hexafluorophosphate-1-hydroxybenzotriazole mediated coupling.
Noda
M
M
Technology Research Laboratory, Shimadzu Corporation, Kyoto, Japan. m-noda@shimadzu.co.jp
Kiffe
M
M
D000143:Acids; D000596:Amino Acids / Q000032:analysis; D001120:Arginine / Q000031:analogs & derivatives* / Q000737:chemistry; D004355:Drug Stability; D005449:Fluorenes / Q000737:chemistry*; D006146:Guanidines / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis*
D000143:Acids; D000596:Amino Acids; D005449:Fluorenes; D006146:Guanidines; C110467:N(alpha)-fluorenylmethoxycarbonylarginine; D010455:Peptides; D001120:Arginine