Tetracyclines chloro derivative

The 7-chloro-derivative, the first of the group to be isolated (1948) is known as chlortetracy-cline. The 5-hydroxy-derivative is oxytetracy-dine. More recently introduced tetracyclines are 6-demethyl-7-chlorotetracycline and 5-hydroxy-6-deoxy-6-methyienetetracycline. 

Tetracycline 4.46) and its derivatives are the most used of all broad-spectrum antibiotics . Their selectivity depends on their preferential accumulation by bacteria, as was outlined in Section 3.0. Chelation of magnesium also plays an important part in their action, and this is discussed in Section 11.8. Tetracycline was prepared by the dechlorination of its 7-chloro-derivative ( Aureomycin ), the first medicinal tetracycline, isolated in 1947 from Streptomyces aureofadens. It is a dimethylaminopentahydroxydioxo-octahydromi/>/Aac carboxamide. 

The unexpected biological activities of tetracyclines, such as 5a-epi-6-epitetracychne [19543-88-5] C22H24N20g, and 7-chloro-5a,lla-dehydro-6-epitetracycline [22688-60-4] C22H22ClN20g, make predicting stmcture-activity relationships difficult (64). Aside from the C-2 amide Mannich-base derivatives, variation at other centers in the molecule, ie, C-4, 4a, 5a, 12a, decreases the biological activity. 

Structural susceptibilities and structure/activity studies have both inspired a large amount of semi-synthetic vrork to find more stable compounds without loss of antibacterial activity. The less active 6p methyl isomer of doxycycline (6) has been derived from oxytetracycline (3 R = OH) by catalytic reduction.. Treatment of (3) with N-chlorosuccinimide followed by hydrofluoric acid gave the chloro compound (X) which upon catalytic reduction afforded doxycycline (6), the 6a compound together with the less active 6p isomer (refs.250, 251) by saturation of the methylene group and removal of chlorine from (X). Reductive treatment of (X) with sodium hydrosulphite produced methacycline (5). The corresponding 5-deoxy analogues have likewise been derived by using tetracycline (3 R = H) in the same reaction sequences. 

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