Esters, antimicrobial

Kabara, J.J. 1986. Fatty Acids and Esters Antimicrobial/Insecticidal Agents. ACS Symposium Series. 325 220-238... 

Sodium trichloroacetate [650-51-17, C2Cl202Na, is used as a herbicide for various grasses and cattails (2). The free acid has been used as an astringent, antiseptic, and polymerisation catalyst. The esters have antimicrobial activity. The oral toxicity of sodium trichloroacetate is quite low (LD q rats, 5.0 g/kg). Although very corrosive to skin, trichloroacetic acid does not have the skin absorption toxicity found with chloroacetic acid (28). 

Mocimycin has been chemically converted to aurodox by protection of the 4-hydroxy group at the pyridone moiety as the benzoylformate, followed by /V-methylation and hydrolytic removal of the protective group (1,55). Whereas aurodox esters are active growth promotors in animals, goldinamines that are A/-acylated by acids other than goldinonic acid, such as acetic, benzoic, or arylsulfonic acids, lack useful antimicrobial or growth-promoting activity (1). 

The threat of accidental misuse of quaternary ammonium compounds coupled with potential harmful effects to sensitive species of fish and invertebrates has prompted some concern. Industry has responded with an effort to replace the questionable compounds with those of a more environmentally friendly nature. Newer classes of quaternaries, eg, esters (206) and betaine esters (207), have been developed. These materials are more readily biodegraded. The mechanisms of antimicrobial activity and hydrolysis of these compounds have been studied (207). AppHcations as surface disinfectants, antimicrobials, and in vitro microbiocidals have also been reported. Examples of ester-type quaternaries are shown in Figure 1. 

The acid-instabihty of erythromycin makes it susceptible to degradation in the stomach to intramolecular cyclization products lacking antimicrobial activity. Relatively water-insoluble, acid-stable salts, esters, and/or formulations have therefore been employed to protect erythromycin during passage through the stomach, to increase oral bioavakabihty, and to decrease the variabiUty of oral absorption. These various derivatives and formulations also mask the very bitter taste of macroHdes. 

Table 4. Physical and Antimicrobial Properties of />Hydroxybenzoic Acid Esters ...

Organic acids may inhibit growth when present in the undissociated form because of their abiHty to change the pH inside the ceU. The most efficient are benzoic acid and sorbic acid, but formic, acetic, and propionic acid also have this effect. The parabens, ie, -hydroxy benzoic acid esters, are also used because of their antimicrobial effect over a broad pH range. 

In another study, the carrier protein was replaced by an enzyme compatible solid-phase resin (PEGA), and enzyme-catalyzed cyclization was used to probe substrate specificity. This study demonstrated also that oxo-esters are tolerated as substrates for TE domains, and then-preparation in library format served as an excellent tool for substrate specificity studies, as well as for preparation of cyclized peptides. Figure 13.11 shows how the TycA TE showed selectivity for only residues 1 and 9 (colored in red), and changes at all other residues were tolerated [42]. Hydrogen bonding interactions are shown in green. Several compounds made from this series were shown to demonstrate improved therapeutic indices (with respect to hemolysis) while retaining antimicrobial activity. 

Raghavan and coworkers have reported on the preparation of 4-hydroxybenzoic add esters (parabans) possessing antimicrobial activity by esterification of 4-hydroxybenzoic acid (Scheme 6.153) [299]. Optimum results were obtained using the alcohol (1-butanol) as solvent in the presence of catalytic amounts of zinc(II) chloride or p-toluenesulfonic acid (pTsOH) under atmospheric conditions. After 5 min of microwave irradiation at 120 °C, ca. 40% conversion to the ester was observed. Related studies on the synthesis of long-chain aliphatic esters have been described by Mariani and coworkers [300]. 

Diazoimidazole-5-carboxylic acid esters have inhibitory activity in several different types of microorganisms. They can be used as sanitizing compounds (72USP3654257). In particular, methyl 4-diazoimidazole-5-carboxylate showed antimicrobial activity towards strains of microorganisms resistant to the action of certain known chemotherapeutic agents. 

The antifungal properties of fatty acids and several of their derivatives such as amides and methyl esters have been reviewed (113) as have their antimicrobial activities (114). Monolaurin (the ester of 1 auric acid and glycerol) is the most potent lipid derivative tested to date with regard to antibiotic activity. 

The lipophilic character of their hydrocarbon skeleton and the hydrophilic character of their functional groups are of main importance in the antimicrobial action of EO components. Therefore, a rank of activity has been proposed as follows phenols>aldehydes>ketones>alcohols>esters>hydrocarbons [10]. 

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