Hydrolysis of phosphorus(V) esters and phosphonoacetates by cyclodextrins, copper(II) metallomicelles, and other nucleophilic agents.

摘要

This dissertation explores the hydrolytic reactivity of phosphonoacetate, phosphotriester, and phosphonothioate substrates.; Chapter 1 is mainly concerned with the synthesis, deuterium exchange, and the hydrolysis of a variety of charged phosphonoacetates, substrates that contain both a phosphonate monoester and a carbonyl ester separated by a spacer methylene. The hydrolysis reactions were conducted in aqueous solutions and used acid, base, and the metal cations: Th(IV) and Zr(IV), in acidic solution. In moderately basic solutions (pH ∼ 10), deuterium exchange kinetics at the spacer methylene was measured. In very basic solutions (pH ∼ 13) cleavage of the carbonyl ester was observed. Solutions of Th(IV) were shown to cleave the carbonyl ester. Zr(IV) solutions also preferentially hydrolyzed the carbonyl ester except when the phosphonate monoester had a highly activated leaving group. Thus, the influences of various ester substituents in terms of kinetics and regioselectivity on PA substrate deuterium exchange and on metal ion catalyzed and base-promoted hydrolysis were compared.; Chapter 2 describes the hydrolysis of phosphotriester substrates induced by cyclodextrins (CD's). Thus, the native α-, β-, and γ-CD's were utilized in the basic (pH 10) cleavages of p-nitrophenyl diphenylphosphate (PNPDPP), p-nitrophenyl 1,8-naphthylphosphate (PNPNP), and p-nitrophenyl biphenylphosphate (PNPBPP). Rate constants and extracted kinetic parameters revealed interesting patterns for the complementarity between the CD hosts and their phosphotriester guests. Kinetic studies demonstrated that β-CD was substantially selective for PNPNP hydrolysis. Hydrolysis of PNPNP by β-CD was inhibited by naphthalene 2-carboxylate.; Chapter 3 is a discussion of the synthesis and the subsequent hydrolysis of a stereochemically well-defined phenylphosphonothioate substrate, Me-EPN. Hydrolysis of this substrate by a Cu(II) metallomicelle in micellar solutions showed an essentially complete inversion of configuration at the substrate P center which was identical, in terms of stereochemical course, to hydrolysis by concentrated hydroxide.