Erythromycin ethyl carbonate

Semisynthetic Derivatives. Erythromycin has been the principal subject of modification of 14-membered macrolides some of the derivatives are being commercially launched. Derivatives of erythromycin and oleandomycin include 2-U-nee ly I erythromycin (C331129NO t. 2 -O-propionylerythromycin (QoHtiNOm), erythromycin ethyl carbonate (C/0H71NO15), erytliromydn ethyl succinate (C 3H75NOi2), tn-O-acetyloleandomycin (C4iHc7NOi5), erythromycin-11,12-carbonate... 

Ester derivatives of erythromycin, shown in Table 4, were synthesized soon after its discovery (124—126). They are readily prepared by acylation of the 2-hydroxyl group the neighboring 3r-dimethylamino group directs acylation to this site. Commonly used esters of erythromycin are propionate, acetate, ethyl succinate, and ethyl carbonate (30). 2r-Esters do not bind bacterial ribosomes, however, and consequently must be hydrolyzed back to the parent to exert antibacterial activity (127). Ester derivatives are still being prepared (128,129). 2,-0-Acetylerythromycin stearate, also known as erythromycin acistrate, is an example undergoing clinical trial (11,130,131). Two salts of 2,-0-propionyl-erythromycin, N-acetylcysteinate (erythromycin stinoprate) and mercaptosuccinate, were prepared to combine antibiotic and mucolytic properties in a single agent (132—134). 

Typical procedure. 2 -Acetyl-4"-O-benzyloxycarbonyl-G-O-methyl-erythromycin A 11,12-carbonate 920 [660] A solution of diol 919 (0.51 g, 0.55 mmol) in THF (10 mL) at —35 °C was treated with sodium bis(trimethylsilyl)amide in THF (0.7 mL of a 0.84 M solution 0.6 mmol). After 10 min, a solution of CDI (0.33 g, 2.0 mmol) in THF (5 mL) was added. The reaction mixture was allowed to warm to room temperature and kept at this temperature for 15 min. It was then cooled to 0-5 °C (ice/ water bath) and 0.5 m NaH2P04 solution was added. The aqueous layer was extracted twice with ethyl acetate. The combined organic layers were dried (magnesium sulfate) and concentrated to a yellow oil. The residue was purified by flash chromatography eluting with acetonitrile/dichloromethane/concentrated ammonium hydroxide (1 1 0.01) to afford 370 mg (70%) of carbonate 920 mp 248-250 °C IR (CDCI3) Vmax = 1800 cm (cyclic carbonate C=0). 

For the quantitative determination of erythromycin and oleandomycin in animal tissues, milk, and eggs, a TLC method has been described (44) in which 25 g of sample are homogenized with 90 ml of acetonitrile and 2 ml of saturated sodium carbonate solution and centrifuged. Then 3 g of sodium chloride are added to the supemate and the extraction is done with 50 ml of dichloromethane. The organic layer is dried with 5 g of anhydrous sodium sulfate, filtered through cotton wool, evaporated to dryness, and dissolved in ethyl acetate, followed by different washing steps. 

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