Chemistry and Synthesis of Tetracyclines

The tetracyclines are all structurally related by their having a naphthacene ring system and they differ only in the pattern of substituent groups. 

The structure of seven important tetracyclines, namely tetracycline (1), chlorotetracycline(7-chlorotetracycline)(2), oxytetracycline (3) [5- 

The usual ring numbering is shown and the parent compound tetracycline (1) is 4a-dimethylamino-1,4,4aa,5,5aa,6,11,12a-octahydro-3,6p,10,12,12aa-pentahydroxy-6a-methyl-1,11-dioxonaphthacene-2-carboxamide, although the trivial or generic name tetracycline is clearly preferable. A wide variety of trade names abound. 

The determination of the structure of oxytetracycline involving at that time only degradative evidence, uv and ir spectroscopy was achieved in 1953 (ref. 244). Fermentation methods are employed as with most antibioics and selected strains of Streptomyces are cultivated to secure optimum growth and maximum formation of the product in a bioreactor at constant temperature in a sterile nutrient medium containing a carbon and a nitrogen source together with 

In this complex system of functional groups, once termed a diabolical concatenation (ref. 248), structure/activity relationships indicate firstly that functional groups at positions 5,6 and 7 may be dispensed with without drastically affecting antibacterial properties, secondly the natural configurations at C-4 and C-5a are necessary and thirdly, loss of hydrogen from C-5a and C-11a causes loss of activity. The Cl 1, C12 diketone system is thought to be vital (ref. 249) and the presenration of the BCD chromphores important, o-Substitution of the phenolic group is deleterious. 

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