Chlortetracycline chemical structure

The tetracyclines are a group of drugs with a common basic chemical structure and pharmacological activity. The first tetracycline, chlortetracycline was isolated from... 

The tetracyclines are a group of antibiotics with the same basic chemical structure they are derivatives of the naphthacene ring system. Compounds of the series differ in the composition of the side chains (Fig. 1). These antibiotics derived from different Streptomyces species show closely related spectra of bacteriostatic properties, with the exception of minocycline, which is very effective against most Staphylococcus strains resistant to other tetracyclines. Absorption, metabolism, and excretion of the different tetracyclines vary, however. After oral application, tetracycline, oxytetracycline, and chlortetracycline are absorbed to a much lesser degree than demethylchlortetracycline, methacycline, or the almost entirely absorbed minocycline. Maximum blood levels are found 2-6 h after oral intake and immediately in the case of intravenous infusion. Half-lives between 8 and 15 h were reported. The tetracyclines diffuse readily across the vascular barrier and are found in various tissues such as the liver, spleen, bone marrow, kidney, skin, and lungs as well as the peritoneal and pericardiac cavities. The tetracyclines are also able to... 

Fig. 1 a-h. Chemical structures of the tetracyclines, a tetracycline b oxytetracycline c chlortetracycline d methacycline e demethylchlortetracycline f 6-deoxytetracycline (doxycycline) g minocycline h roli(A -pyrrolidinomethyl)tetracycline... 

During the course of experiments for the elucidation of the structure of the two earlier discovered compounds chlortetracycline (CTC) and oxytetracycline (OTC) it was found that hydrogenation of chlortetracycline resulted in halogenolysis and the product tetracycline (TC) retained the useful activity spectrum of the first two members of the family. TC appears to represent the first clinically successful antibiotic produced by shere chemical manipulation of preexisting antibiotic. TC was found to be present in fermentations of both cultures streptomyces aureofaciens and streptomyces rimosus as well as in streptomyces viridofaciens (1). 

Oxytetracydine Hydrochloride, USP. Early in I9.W, Finlay et al. " reported the isolation of oxytetracycline (Tei-ramycin) from S. rimosus. This compound was swai idemi-fied as a chemical analogue of chlortetracycline that showed similar antibiotic properties. The structure of oxytetracydine was elucidated by Hochstein et al.. "- and this work provided the basis fur the conllmiation of the structure of the other tetracyclines. 

One year later, the American pharmaceutical company Pfizer discovered a related structure - christened oxytetracycline (Terramycin) - from Streptomyces rimosus. Interestingly, this was found in a soil sample located near their factory in Terre Haute, Indiana. The parent structure - tetracycline - was then obtained by chemical removal of the chlorine atom (an element only rarely found in terrestrial organisms but common in natural products from marine organisms) from chlortetracycline. This third antibacterial agent was subequently found naturally as a constituent of both Streptomyces aureofaciens and Streptomyces viridifaciens. The structures of chlortetracycline were established by R.B. Woodward in 1952 and that of oxytetracycline by Pfizer scientists (in collaboration with RBW) in 1952. 

---