Nomenclature The nomenclature of penicillins is somewhat complex and very cumbersome. Two numbering systems for the fused bicyclic heterocyclic system exist.

The Chemical Abstracts system initiates the numbering with the sulfur atom and assigns the ring nitrogen the 4-position. Thus, penicillins are named as 4-thia-l-azabicyclo[3.2.0]heptanes, according to this system. The numbering system adopted by the USP is the reverse of the Chemical Abstracts procedure, assigning number 1 to the nitrogen atom and number 4 to the sulfur atom. Three simplified forms of penicillin nomenclature have been adopted for general use. The first uses the name “penam” for the unsubstituted bicyclic system, including the amide carbonyl group, with one of the foregoing numbering systems as just described.

Thus, penicillins generally are designated according to the Chemical Abstracts system as 5-acylamino-2,2-dimethylpenam-3-carboxylic acids. The second,seen more frequently in the medical literature, uses the name “penicillanic acid” to describe the ring system with substituents that are generally present (i.e., 2,2-dimethyl and 3-carboxyl). A third form, followed in this chapter, uses trivial nomenclature to name the entire 6-carbonylaminopenicillanic acid portion of the molecule penicillin and then distinguishes compounds on the basis of the R group of the acyl portion of the molecule.

Thus, penicillin G is named benzylpenicillin, penicillin V is phenoxymethylpenicillin, methicillin is 2,6-dimethoxyphenylpenicillin, and so on. For the most part, the latter two systems serve well for naming and comparing closely similar penicillin structures, but they are too restrictive to be applied to compounds with unusual substituents or to ring-modified derivatives.

Synthesis Naturally occurring penicillin produce by formation ,there are 3 methods for syntheses .

1- Sheehan and Henery-Logan adapted techniques developed in peptide synthesis to the synthesis of penicillin V. This procedure is not likely to replace the established fermentation processes because the last step in the reaction series develops only 10% to 12% penicillin. It is of advantage in research because it provides a means of obtaining many new amide chains hitherto not possible to achieve by biosynthetic procedures.

2- A group of British scientists, Batchelor et al 2- A group of British scientists, Batchelor et al.16 reported the isolation of 6-APA(6-amio penicillanic acid) from a culture of P. chrysogenum. This compound can be converted to penicillins by acylation of the 6-amino group. 3- Sheehan and Ferris provided another route to synthetic penicillins by converting a natural penicillin, such as penicillin G potassium, to an intermediate (Fig. 8.1), from which the acyl side chain has been cleaved and which then can be treated to form biologically active penicillins with various new side chains.

Chemical Degradation The early commercial penicillin was a yellow-to-brown amorphous powder that was so unstable that refrigeration was required to maintain a reasonable level of activity for a short time. Improved purification procedures provided the white crystalline material in use today. Crystalline penicillin must be protected from moisture, but when kept dry, the salts will remain stable for years without refrigeration. Many penicillins have an unpleasant taste, which must be overcome in the formation of pediatric dosage forms.

All of the natural penicillins are strongly dextrorotatory All of the natural penicillins are strongly dextrorotatory. The solubility and other physicochemical properties of the penicillins are affected by the nature of the acyl side chain and by the cations used to make salts of the acid. Most penicillins are acids with pKa values in the range of 2.5 to 3.0, but some are amphoteric .The free acids are not suitable for oral or parenteral administration.

The sodium and potassium salts of most penicillins, however, are soluble in water and readily absorbed orally or parenterally. Salts of penicillins with organic bases, such as benzathine, procaine, and hydrabamine, have limited water solubility and are, therefore, useful as depot forms to provide effective blood levels over a long period in the treatment of chronic infections.

Some of the crystalline salts of the penicillins are hygroscopic and must be stored in sealed containers. The main cause of deterioration of penicillin is the reactivity of the strained lactam ring, particularly to hydrolysis. The course of the hydrolysis and the nature of the degradation products are influenced by the pH of the solution.