Synthesis and comparative study on the reactivity of peptidyl-type phosphinic esters: intramolecular effects in the alkaline and acidic cleavage of methyl beta-carboxyphosphinates.
Using the phosphinic analogue of Cbz-Phe-Gly-OEt 1a as a template for this study, several phosphinic esters (2a-g) were prepared, employing an efficient method for each case. The reactivity of these derivatives under conventional deprotection conditions was studied, and the results are listed comparatively. The effect of steric hindrance as well as the contribution of neighboring groups in the rate of hydrolysis of suitably selected beta-carboxyphosphinates under acidic and alkaline deprotection conditions was examined. The results clearly demonstrate that a significant acceleration of phosphinate cleavage occurs due to the intermediacy of a five-membered, mixed anhydride-type species. This was supported by the observation that similar interactions were not observed in the case of hindered alpha-carboxyphosphinate homologous derivatives.
Georgiadis
D
D
Department of Chemistry, Laboratory of Organic Chemistry, University of Athens, Panepistimiopolis Zografou, 15771, Athens, Greece.
Dive
V
V
Yiotakis
A
A
D002264:Carboxylic Acids; D002384:Catalysis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D010455:Peptides / Q000737:chemistry*; D010721:Phosphinic Acids / Q000737:chemistry*; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry
D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D010455:Peptides; D010721:Phosphinic Acids; D011480:Protease Inhibitors; D008666:Metalloendopeptidases