Deslongchamps’ theory

The preferred bond cleavage In the polymerization of these blcycllc acetals and orthoesters Is determined by Deslongchamps theory. If all oxygens are equally preferred by the former, the p-character of the oxygen atom, determined by the bond angles, will be the dominant factor. 

In a study of the relative rates of hydrolysis of conformationally restrained a- and jS-4-pentenyl glucosides under neutral conditions, it was concluded that the Deslongchamps theory for glycoside hydrolysis (the anti-periplanar lone pair hypothesis) was not consistent with the results obtained. In work on variously substituted 4-pentenyl glycosides compound (55, either anomer) gave the amide (56) on treatment with N-bromosuccinimide in aqueous acetonitrile, whereas the benzylated analogue (57) underwent hydrolysis in these conditions (Scheme 20). The first result was attributed to the strain imposed by the ring fusions on the pyranose system. 

Finally, it should be mentioned that a concept of torsional strain of amide bonds was also developed by W. L. Mock in 1976 and applied to the mode of action of carboxypeptidase A (121). It involves a torsion of the amide bond to allow either cis or trans addition of the nucleophile and the proton on the developing orbitals in the transition state. This principle complements Deslongchamps theory of optimum geometry of the transition state tetrahedral intermediate. 

The first indication that this relationship can be a very simple one arose as part of an investigation of stereoelectronic effects in acetal hydrolysis. According to Deslongchamps (1983) theory of stereoelectronic control (see also Sinnott, 1988), the orientation of lone-pair electrons can control reactivity in appropriate systems. In its original form the theory suggested... 

In this book Pierre Deslongchamps, an investigator who has made seminal contributions to the stereoelectronic theory, brings together the experimental data and his conclusions derived from them. It is particularly timely that this be done since, by their very nature, stereoelectronic effects are quite subtle and to see the thread of their influences a large body of experimental data is essential. A similar circumstance applied during the formative years of Robinson s theory. 

Deslongchamps has proposed that in the reactions of tetrahedral intermediates in the hydrolysis of esters and amides the group which leaves is that which has two antiperiplanar lone pairs of electrons in the case of oxygen the two lone pairs are considered as identical sp hybrids, the antiperiplanar one making a dihedral angle of 180° with the bond to be cleaved [37]. The theory as originally formulated considered the lifetime of these intermediates to be short compared to the time of rotation about a C—O or C—N single bond, which has since been shown to be demonstrably incorrect [38,39]. 

An energy decomposition scheme in terms of classical theory proposed by Grein and Deslongchamps (163) is discussed in Section II.I. 

If it is assumed that effects on the ground state are amplified in the transition state, this purely empirical thermodynamic anomeric effect is transformed into a predictive kinetic anomeric effect (Kirby, 1983). In the transition state for breakdown of a tetrahedral species containing the X—C—X—C fragment, breakdown of the isomer with the scissile bond antiperiplanar to a heteroatom lone pair will proceed more rapidly, under stereoelectronic acceleration (Scheme 17). The theory has obvious utility in predicting product distribution when a single species may break down by a number of possible pathways (Deslongchamps, 1983). However, the hypothesis has not been without its detractors. Some of the experimental work used... 

Deslongchamps G, Deslongchamps P (2011) Bent bonds, the antiperiplanar hypothesis and the theory of resonance. A simple model to understand reactivity in organic chemistry. Org Biomol Chem 9(15) 5321-5333. doi 10.1039/Clob05393k... 

It is reasonable to inquire whether recognition of such a concept might apply to mechanistic ideas about enzyme reactions. It now appears that the stereoelectronic theory that Deslongchamps and co-workers have developed is specifically applicable to peptide hydrolyses by serine proteases. Hydrolysis of simple esters will be used first to illustrate the approach. 

Deslongchamps kindly provided us with his own view of the mechanistic path by which a-chymotrypsin and other serine proteases can hydrolyze secondary amides by stereoelectronic control (Fig. 4.7). Petkov et al. (119) also arrived at a similar proposal by studying the influence of the leaving group on the reactivity of specific anilides in a-chymotrypsin-catalyzed hydrolysis. Furthermore, the stereoelectronic control theory has been applied to the mode of action of ribonuclease A, staphylococcal nuclease and lysozyme (120). 

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