Amino, generally acids

Step from general acid-catalyzed formation of immonium ions to general base-catalyzed hydration of these ions to the amino alcohol [Eq. (6)]. 

Electrochemical fluorination of cyclic 2-(dialkylamino)-propionic acids provides a general route to optically active perfluoro-(2-cycIic(dialkyl-amino)-propionic acids [91 JFC(52) 133], which are a source of perfluorinated vinylamines (88CL1887). 

Amino Acid Side Chain as General Acid. 158... 

A similar bait and switch approach has been exploited for acyl-transfer reactions (Janda et al., 1990b, 1991c). The design of hapten [10] incorporates both a transition state mimic and the cationic pyridinium moiety, designed to induce the presence of a potential general acid/base or nucleophilic amino acid residue in the combining site, able to assist in catalysis of the hydrolysis of substrate [11] (Appendix entry 2.6). 

General acid catalysis is schematized in Fig. 7J,b. Here, an acid A-H increases the polarity of the carbonyl group and, hence, the electrophilicity of the carbonyl C-atom. For entropy reasons, the reaction is greatly facilitated when it is an intramolecular one (Fig. 7J,b2), in other words, when the general acid catalyst is favorably positioned within the molecule itself. Such a mechanism is the one exploited and refined by nature during the evolution of the hydrolases, with the general acid catalyst and the H20 molecule replaced by adequate amino acid side chains, and the enzymatic transition state being de facto a supermolecule (see Chapt. 3). 

Belke et al. (1971) reported general base and general acid catalysis in cyclization of 2-hydroxymethylbenzamide [equation (18)]. However, with 2-hydroxymethyl-6-aminobenzamide strict general base catalysis by buffer bases is observed with a Bronsted coefficient of O 39 (Fife and Benjamin, unpublished data). In contrast with the unsubstituted amide, the Bronsted plot is nicely linear. An amino-group in the 6-position might assist decomposition of a tetrahedral intermediate as in [37a, b] or a kinetic equivalent. The pH-rate constant profile for spontaneous cyclization at zero buffer concentra-... 

The active site of the aldolase enzyme is believed to be as shown (Figure 13.7). Although several amino acid residues are involved with bonding the substrates at the active site, the critical amino acid residues are a lysine and an aspartic acid residue. The lysine forms a substrate-enzyme bond via an imine linkage, and the aspartic acid residue functions as a general acid-base. 

FIGURE 6-9 Amino acids in general acid-base catalysis. Many... 

---