Synthesis and Comparative Study on the Reactivity of Peptidyl-Type Phosphinic Esters: Intramolecular Effects in the Alkaline and Acidic Cleavage of Methyl β-Carboxyphosphinates
- 5 September 2001
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 66 (20), 6604-6610
- https://doi.org/10.1021/jo0156363
Abstract
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 β-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 α-carboxyphosphinate homologous derivatives.Keywords
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