Erythromycin acid hydrolysis

Erythromycin estolate differs from other forms of erythromycin in that it is extremely stable to acid hydrolysis.5 Erythromycin liberated from the ester by mild alkaline hydrolysis is subject to rapid decomposition in strongly acid solutions. Kavanagh has stated that deterioration of erythromycin increases with an increase in temperature and decreases with an increase in pH up to 8.0. Buffered aqueous solutions of erythromycin base are quite stable at this pH. Acetone solutions of the ester form are stable, while acetone solutions of the propionyl erythromycin lauryl sulfate preparation are not. Powders and dry formulations are stable for at least five years. Liquid preparations become unacceptable after 2 years due to undesirable taste. 

In some cases enzymes can increase the rate of reaction by up to lO times. Carnell and Roberts (1997) have briefly discussed the scope of biotransformations that are used to make pharmaceuticals like penicillins, cephalosporines, erythromycin, lovastatin, cyclosporin, etc., and for food additives like citric acid, L-glutamate, and L-lysine. A very successful transformation by Zeneca has been that of benzene reduction, with Pseudomonase Putida, to dihydrocatechol and catechol the dihydro derivative is used to produce (+/-) pinitol. Fluorobenzene has been converted to fluorodihydrocatechol, an intermediate for pharmaceuticals. The highly stereo selective Bayer-Villeger reaction has been carried out with genetically engineered S-cerevisvae. Hydrolases have allowed enantioselective, and in some cases regioselective, hydrolysis of racemic esters. 

Modification of Chemical Structure of Drug The use of a Hammett linear free-energy relationship to investigate the effects of substituents on the rates of aromatic side-chain reactions such as hydrolysis of esters has been alluded to earlier vis-a-vis attainment of optimum stability [9,10]. Degradation of erythromycin under acidic pH conditions is inhibited by substituting a methoxy group for the C-6 hydroxyl as found for the acid stability of clathromycin, which is 340 times greater than that of erythromycin [70]. 

Lazarevski, T., Radobolja, G., and Djoklc, S. (1978). Erythromycin VI Kinetics of acid-catalyzed hydrolysis of erythromycin oxime and erythromycylamine. J. Pham. Sci. 67, 1031-1033. 

The structure of desosamine was elucidated independently in three laboratories. Clark examined the hydrolysis of erythromycin with 6 N hydrochloric acid. In addition to a tar soluble in organic solvents, a water-soluble, reducing base was isolated as a crystalline hydrochloride having the formula CsHitNOs-HCI. This product was found to consume 2 moles of periodate per mole with the formation of 1 mole of dimethylamine, 2 moles of formic acid, and 1 mole of aldol, but no formaldehyde. The aldol was isolated as the (2,4-dinitrophenyl)hydrazone of crotonaldehyde, the dehydration product of aldol. A C-methyl group was detected by the iodoform reaction. The dimethylamino group was readily eliminated under alkaline conditions, suggesting that it was present in a position /3 to the... 

Esters of the 3-carboxylic acid group of ampicillin (Section 13.1) are used as pro-drugs, e.g. bacampicillin, talampicillin, and pivampicillin. Their more lipophilic properties ensure better oral absorption. The active drug is liberated by the non-specific esterases of the bloodstream. Esters of erythromycin 4.47)., such as the stearate or ethyl succinate, survive the stomach s acidity, which erythromycin does not, but are hydrolysed back to the true drug in the duodenum. Children, who intensely dislike the bitter taste of chloramphenicol, are given the succinate ester. In both cases, hydrolysis liberates the true drug. 

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