Amino acid ester chelates preparation

The ability of a metal ion to increase the rate of hydrolysis of a peptide has enormous implications in biology, and many studies have centred upon the interactions and reactions of metal complexes with proteins. However, hydrolysis is not the only reaction of this type which may be activated by chelation to a metal ion, and chelated esters are prone to attack by any reasonably strong nucleophile. For example, amides are readily prepared upon reaction of a co-ordinated amino acid ester with a nucleophilic amine (Fig. 3-11). In this case, the product is usually, but not always, the neutral chelated amide rather than a depro-tonated species. 

The six amino acids 63 were prepared individually, and mixed to give acids M-64 (see Scheme 13.15) [51]. Esterification of M-64, zinc-chelated ester enolate Claisen rearrangement of M-65, tert-butyl esterification, and removal of the Me3Si group yielded M-66. The alkynyl allenes M-67 were obtained by Af-propargylation. The allenic Pauson-Khand reaction of M-67 afforded three products (/ )-alkylidenecyclopentenone... 

Liquid chromatographic resolutions based on highly selective host-guest, metal chelate and charge-transfer com-plexations have been described (1,2). Recently, a chiral diamide-bonded stationary phase (I) has been prepared, which relies entirely on hydrogen bond associations for the material to be resolved. Despite the weak and flexible interaction in this system, direct resolution of enantiomeric N-acyl-fl-amino acid esters (II) was accomplished with the advent of a highly efficient column technology (2- ). 

The cobalt(III)-promoted hydrolysis of amino acid esters and peptides and the application of cobalt(III) complexes to the synthesis of small peptides has been reviewed. The ability of a metal ion to cooperate with various inter- and intramolecular acids and bases and promote amide hydrolysis has been investigated. The cobalt complexes (5-10) were prepared as potential substrates for amide hydrolysis. Phenolic and carboxylic functional groups were placed within the vicinity of cobalt(III) chelated amides, to provide models for zinc-containing peptidases such as carboxypeplidase A. The incorporation of a phenol group as in (5) and (6) enhanced the rate of base hydrolysis of the amide function by a factor of 10 -fold above that due to the metal alone. Intramolecular catalysis by the carboxyl group in the complexes (5) and (8) was not observed. The results are interpreted in terms of a bifunctional mechanism for tetrahedral intermediate breakdown by phenol. 

Transition Metal-Catalyzed Allylie Alkylation. Chelated amino acid ester enolates were found to be suitable nucleophiles for palladium-catalyzed allylie alkylations (eq 25). They were conveniently prepared by deprotonation of a glycine derivative with LHMDS followed by transmetallation with zinc chloride. The palladium-catalyzed allylie alkylation then takes place in the presence of allyl carbonates to produce the desired anti amino acid derivative. ... 

Further variations of the Claisen rearrangement protocol were also utilized for the synthesis of allenic amino acid derivatives. Whereas the Ireland-Claisen rearrangement led to unsatisfactory results [133b], a number of variously substituted a-allenic a-amino acids were prepared by Kazmaier [135] by chelate-controlled Claisen rearrangement of ester enolates (Scheme 18.47). For example, deprotonation of the propargylic ester 147 with 2 equiv. of lithium diisopropylamide and transmetallation with zinc chloride furnished the chelate complex 148, which underwent a highly syn-stereoselective rearrangement to the amino acid derivative 149. 

A numerous series of compounds containing a N,O-chelating ligand, namely the derivatives of anthranilic (157) and 3-amino-2-thiophenecarboxylic (158 and 159) acids, were prepared by the reactions of organohalogermanes with esters, amides or lithium derivatives of acids510-516. 

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