Benzylpenicillin protection

An alternate route to ampicillin not only circumvents the need for 6-APA but also has the advantage of providing a prodrug form of ampicillin as well as the parent compound. Reaction of benzylpenicillin (4) with the acid protecting group, 29, gives the formol ester, 30. Reaction of the product with phosphorus pentachloride leads to the corresponding imino chloride (31). 

The complex outer layers beyond the peptidoglycan in the Gram-negative species, the outer membrane, protect the organism to a certain extent from the action of toxic chemicals (see Chapter 13). Thus, disinfectants are often effective only at concentrations higher than those affecting Gram-positive cells and these layers provide unique protection to the cells from the action of benzylpenicillin and lysozyme. 

Procedure Weigh accurately about 0.1 g of benzylpenicillin in DW and dilute to 100 ml in a volumetric flask. Transfer 10.0 ml to an iodine flask, add 5 ml of N sodium hydroxide and allow to stand for 20 minutes. Now, add 20 ml of freshly prepared buffer solution, 5 ml of N HC1 and 25.0 ml of 0.02 N iodine solution. Close the flask with a wet glass-stopper and allow to stand for 20 minutes in a dark place (i.e., protected from light). Titrate the excess of iodine with 0.02 N sodium thiosulphate, employing freshly prepared starch solution as an indicator added towards the end-point. 

Aminophylline Aminophylline should not be mixed with acidic drugs, as it becomes precipitated if the pH of the final solution falls below pH 8. Mixture with glucose may increase the pH above 10 where proteins, such as insulin and erythromycin, are unstable. Some drugs that are incompatible with aminophylline include amiodarone, benzylpenicillin potassium, cisatracurium, ceftazidime, ceftriaxone, dobutamine, tetracycline hydrochloride, verapamil hydrochloride, warfarin sodium, and vitamin B and C injection. Alcohol-free theophylline should be stored in amber-colored containers maximum care must be taken to protect it against exposure to light.92-94... 

Clavulanic acid was discovered in 1976 and is a P-lactam antibiotic with low antibiotic activity, but does protect p-lactamase-sensitive compounds of high intrinsic activity such as benzylpenicillin, ampicilhn, and amoxicillin from p-lactamase destruction. Subsequently other p-lactamase inhibitors such as sulbactam and tazobactam were developed [4]. 

I wrote about these findings to Howard Florey, who was then in Australia helping to set up the National University at Canberra. His interest was at once aroused. On his return to Oxford he showed that cephalosporin C had an even lower acute toxicity to mice than benzyl-penicillin and that it could protect mice from infections with penicillinase-producing staphylococci against which benzylpenicillin was ineffective. 

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