Mechanistic study on the Knorr pyrazole synthesis-thioester generation reaction

摘要: Abstract A novel Fmoc-SPPS compatible peptide thioester generation method leveraging Knorr pyrazole synthesis was reported recently. C-terminal hydrazides, pentane-2,4-dione and excess arylthiol were added in one-pot to efficiently produce thioesters acidic aqueous solution at room temperature. To elucidate the detailed mechanism of this reaction origin effect acidity, a theoretical investigation on synthesis-thioester carried out. Our computational results suggest that generally proceeds through three stages: hydrazone formation, formation formation. The rate-determining step is C O bond cleavage stage. formed readily converted presence thiophenol. acidity originates from need for protonation oxygen atoms increase electrophilicity carbonyl group or leaving ability hydroxyl group.