Acid hydrolytic reactions

Resolution of racemic alcohols by acylation (Table 6) is as popular as that by hydrolysis. Because of the simplicity of reactions ia nonaqueous media, acylation routes are often preferred. As ia hydrolytic reactions, selectivity of esterification may depend on the stmcture of the acylatiag agent. Whereas Candida glindracea Upase-catalyzed acylation of racemic-cx-methylhenzyl alcohol [98-85-1] (59) with butyric acid has an enantiomeric value E of 20, acylation with dodecanoic acid increases the E value to 46 (16). Not only acids but also anhydrides are used as acylatiag agents. Pseudomonasfl. Upase (PFL), for example, catalyzed acylation of a-phenethanol [98-85-1] (59) with acetic anhydride ia 42% yield and 92% selectivity (74). 

Penicillin is quite unstable under acid conditions. The penicillin molecule is subject to several hydrolytic reactions, all yielding therapeutically inactive com-... 

Interest in acid-fixing reactive dyes has remained active because of their environmentally attractive features (section 1.7). The freedom from competing hydrolytic reactions potentially offers exceptionally high fixation, extreme stability of the dye-fibre bonds and complete suitability of the unfixed dyes for recycling. In contrast to conventional reactive dyes, sensitisation problems arising from reaction with skin proteins are not anticipated. Unlike the haloheterocyclic reactive dyes, there is no risk of release of AOX compounds to waste waters. Heavy metals are not involved in the application of acid-fixing reactive dyes, nor are the electrolytes or alkalis that normally contaminate effluents from conventional reactive dyeing. 

As mentioned earlier, by far the largest number of zinc enzymes are involved in hydrolytic reactions, frequently associated with peptide bond cleavage. Carboxypeptidases and ther-molysins are, respectively, exopeptidases, which remove amino acids from the carboxyl terminus of proteins, and endopeptidases, which cleave peptide bonds in the interior of a polypeptide chain. However, they both have almost identical active sites (Figure 12.4) with two His and one Glu ligands to the Zn2+. It appears that the Glu residue can be bound in a mono- or bi-dentate manner. The two classes of enzymes are expected to follow similar reaction mechanisms. 

Increased understanding of reaction mechanisms in the 1940s and 1950s pinpointed general acid or base catalysis as likely to be of importance in many hydrolytic reactions. The imidazole nucleus in histidine was the obvious center in proteins to donate or accept protons at physiological pH. The involvement of histidine was shown by photochemical oxidation in the presence of methylene blue (Weil and Buchert, 1951) which destroyed histidine and tryptophan and inactivated chymotrypsin and trypsin. 

The tripeptides in Fig. 6.17 underwent a few breakdown reactions (N-ter-minus elimination, Qm formation, peptide bond hydrolysis), some of which will be considered later in this section. Of relevance here was that, of the two amidated tripeptides, the amide at the C-terminus underwent deamidation predominantly (Fig. 6.17, Reaction a), which, perhaps, explains the somewhat lesser stability compared to the free carboxylic acid forms. While the hexapeptide (6.52, Fig. 6.17) followed a different pattern of decomposition [76b], deamidation was also a predominant hydrolytic reaction at all pH values. Thus, the procedure to extrapolate results from small model peptides to larger medicinal peptides appears to be an uncertain one, since small modifications in structure can cause large differences in reactivity. 

Fig. 8.3. Hydrolytic reactions in the activation of prodrugs of carboxylic acids that incorporate an aminomethyl (R = H or alkyl, R" = H or alkyl) or amidomethyl group (R = acyl, R" = H or alkyl). Reaction a (chemical and/or enzymatic) liberates the drug RCOOH and a carbinolamine or carbinolamide, which then breaks down to formaldehyde and an amine or...

Fig. 10.14. Reactivity ofdiol epoxides (Nu = H20, HCT, or another nucleophile), a) Hydrolytic reaction of diol epoxides to tetrols. b) Internal H-bonding in diol epoxides with syw-config-uration and rendering the distal C-atom more electrophilic (modified from [104]). c) General representation of proton-catalyzed (A-H = H+), general acid catalyzed (A-H = acid), or intra-molecularly catalyzed (A-H = syn-OW group) activation of the distal C-atom toward... 

Fig. 11.15. Mechanisms of ring opening of (R)-thiazolidine-4-carboxylic acids (11.113) as derivatives of and chemical delivery systems for l-cysteine (11.114). Activation was shown to be by nonenzymatic, hydrolytic reaction (Pathway a), or by mitochondrial oxidation (Pathway b) to the (R)-4,5-dihydrothiazole-4-carboxylic acid (11.115), followed by a (presumably nonenzymatic) hydrolysis to the IV-acylcysteine, and then by cytosolic hydrolysis to cysteine [138].

Polyhydroamino acids, thermal, reactions catalyzed by,20 379 aminations, 20 405-408 decarboxylations, 20 394-405 hydrolytic, 20 380-394 metabolic pathways, 20 408 Polyion reagents, seespecific substances Polymer chains, growth of, on Ziegler catalysts, 19 225-228... 

In two different soils under lab conditions, where the pHs were 4.8 and 6.5, respective halfllves of 45 days and 113 days were found (52). The half-life under field conditions Is <1 month but hydroxysImazlne, the major degradation product, may persist (106). The more acidic the soil, the more rapid Is the hydrolytic reaction forming hydroxysImazlne (107). Persistence of slmazlne Increases as soil pH Increases, with maximum persistence at a pH of 6.6, and It Is affected by the method of tillage (108). 

Hydroxyl groups can be introduced by hydrolytic reactions in the electrophilic 2-, 4-and 6-positions, and direct hydrolysis of halopyrimidines can be effected under both acidic and alkaline conditions <1994HC(52)1>. Normally 4-halopyrimidines hydrolyze faster than 2-halo derivatives, but in the case of 2-chloro, 6-di(pyrrolidinyl)pyrimidine 163 and 4-chloro-2,6-di(pyrrolidinyl)pyrimidine 164, the 2-chloro isomer 163 was found to hydrolyze 350 times faster (to 165) than the 6-chloro isomer 164 in 6N HCl, and 1750 times faster in 12N HCl <20060PD921>. This result was interpreted as being due to the transition state for hydrolysis of the 4-chloro isomer involving two more molecules of water (each acting as a base) than the transition state for hydrolysis of the 2-chloro isomer. As the concentration of HCl increases from 6 N to 12 N, there are fewer unprotonated water molecules and thus, hydrolysis of the 4-isomer is less favored. This difference in reactivity was able to be exploited to perform a selective hydrolysis on a production scale <20060PD921>. 

Hydrolytic reactions can also be applied in the synthesis of aldehydes or ketones via the corresponding 1,3-oxazine derivatives. The anion formed from 3-methyl-2-(4-pyridyl)tetrahydro-l,3-oxazine 155 on treatment with BuLi proved to react with various electrophiles (alkyl halides, carboxylic esters, acid chlorides, or aldehydes) exclusively at position 2 of the 1,3-oxazine ring and not at the pyridine nitrogen atom. The readily formed 2,2-disubstituted-l,3-oxazine... 

In retrospect, the postulated mechanism for amic acid back reaction to anhydride and amine as the main pathway to explain hydrolytic instability of the poly(amic acid) system may have prompted the search for more stable systems in the form of derivatized polyfamic acids). Realizing that if proton transfer in the internal acid catalyzed formation of the intermediate illustrated in Scheme 9 (reaction 1) can be prevented, then the potential for the amic acid back reaction might be eliminated [51]. This, of course, can be accomplished in... 

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