Decarboxylation electrostatic effects

In a number of nonenzymatic reactions catalyzed by pyridoxal, a metal ion complex is formed—a combination of a multivalent metal ion such as cupric oi aluminum ion with the Schiff base formed from the combination of an amino acid and pyridoxal (I). The electrostatic effect of the metal ion, as well as the electron sink of the pyridinium ion, facilitates the removal of an a -hydrogen atom to form the tautomeric Schiff base, II. Schiff base II is capable of a number of reactions characteristic of pyridoxal systems. Since the former asymmetric center of the amino acid has lost its asymmetry, donation of a proton to that center followed by hydrolytic cleavage of the system will result in racemic amino acid. On the other hand, donation of a proton to the benzylic carbon atom followed by hydrolytic cleavage of the system will result in a transamination reaction—that is, the amino acid will be converted to a keto acid and pyridoxal will be converted to pyridoxamine. Decarboxylation of the original amino acid can occur instead of the initial loss of a proton. In either case, a pair of electrons must be absorbed by the pyridoxal system, and in each case, the electrostatic effect of the metal ion facilitates this electron movement, as well as the subsequent hydrolytic cleavage (40, 43). 

F. H. Westheimer, Coincidences, decarboxylation, and electrostatic effects, Tetrahedron 1995, 51, 3-20. 

Another of Conant s students was Frank Westheimer (b. 1912), who, after postdoctoral work with Hammett at Columbia, held a post at the University of Chicago (1936-1954) and then returned to Harvard. Westheimer worked in several areas of physical organic chemistry and engaged in other chemistry-based activities, as revealed in an interview conducted in 1995 by Istvan Hargittai.233 For much of his career, Westheimer was essentially a physical organic chemist working in biochemistry and he has himself written reflectively on the discovery of the mechanisms of enzyme action over the period 1947-1963234 and on the application of physical organic chemistry to biochemical problems.235 Westheimer has also contributed, as Tetrahedron Perspective Number 4, an article on Coincidences, decarboxylation, and electrostatic effects , which, he writes, ...allows me to review some of my past .236... 

An attractive alternative synthesis was likewise developed by Firmenich. [105, 106] Pentylcyclopentenol, is enzymatically transesterified with dimethyl malo-nate, whereby the (S)-enantiomer remains unaltered, but this can be racemised in the presence of sulfuric acid. The malonate is converted into an allylsilylke-tene acetal, which is then subjected to a Claisen rearrangement this proceeds under the control of the aUyl alcohol at relatively low temperatures and with high stereoselectivity. After decarboxylation, there follows the key step in the synthesis a n-selective epoxidation with highly electrophilic peroxy-acids, such as peroxytrifluoroacetic acid. The high n-selectivity arises from electrostatic effects between the more electron-rich r-side of the douple bond and the partial... 

The influence of electrostatic effects on pyridoxal 5 -phosphate-dependent enzymic decarboxylation of a-amino acids has been studied using ab initio calculations. " The catalytic ability of molecular receptors on a dibenz[c,/z] acridine skeleton to bind and decarboxylate dibutylmalonic acid has been investigated. ... 

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