Organophosphorus and nitro-substituted sulfonate esters of 1-hydroxy-7-azabenzotriazole as highly efficient fast-acting peptide coupling reagents.
Organophosphorus esters 9, 10, 14, and 15 prepared via reaction of diethyl- and diphenylphosphoryl chloride, di(o-tolyl)phosphinyl chloride, and 2,8-dimethylphenoxaphosphinyl chloride with HOAt are excellent coupling reagents for peptide synthesis which are generally superior to their uronium/guanidinium analogues and HOBt- or HODhbt-derived phosphate ester counterparts in minimizing loss of configuration during segment coupling. The phosphinyl analogues are more shelf-stable than the phosphoryl systems. The new reagents have been tested in segment couplings leading to two tripeptides (20, 21) and a hexapeptide 22. Outstanding utility is also shown for the solid-phase assembly of the ACP decapeptide. Similar results were obtained with the 2- and 4-nitro- and 2,4-dinitrophenylsulfonyl esters derived from HOAt.
Carpino
Louis A
LA
Department of Chemistry, University of Massachusetts, Amherst, Massachusetts 01003, USA. carpio@chem.umass.edu
Xia
Jusong
J
Zhang
Chongwu
C
El-Faham
Ayman
A
D001372:Aza Compounds / Q000737:chemistry*; D004952:Esters; D007202:Indicators and Reagents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009943:Organophosphorus Compounds / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013451:Sulfonic Acids / Q000737:chemistry*; D014230:Triazoles / Q000737:chemistry*
D001372:Aza Compounds; D004952:Esters; D007202:Indicators and Reagents; D009943:Organophosphorus Compounds; D010455:Peptides; D013451:Sulfonic Acids; D014230:Triazoles; C435757:1-hydroxy-7-azabenzotriazole