Tetracycline 7-chloro-,

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. 

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. 

A practical process had earlier been developed for the transformation of chlortetracycline (2) into tetracycline (1) by catalytic hydrogenolysis of the aromatic chloro group. Application of the reaction under suitable conditions to demethylchlortetra-... 

The contents of the tube were then acidified to pH 2 by the addition of sulfuric acid and centrifuged. Examination of the supernatant liquid by paper chromatography employing the methods of 8ohonos et al. Antibiotics Annual (1953-4, page 49), demonstrates the presence of 7-chloro-6-demethyltetracycline, 7-chlorotetracycline and tetracycline. 

Another group of compounds, the tetracyclines, are made by fermentation procedures or by chemical modifications of the natural product. The hydrochloride salts are used most commonly for oral administration and are usually encapsulated because of their bitter taste. Controlled catalytic hydrogenolysis of chlortetracycline, a natural product, selectively removes the 7-chloro atom and produces tetracycline. Doxycycline and minocycline are other important antibacterials. Tetracycline can be prescribed for people allergic to penicillin. Doxycycline prevents traveler s diarrhea. Tetracyclines help many infections including Rocky Mountain spotted fever, Lyme disease, urinary tract infections, bronchitis, amoebic dysentery, and acne. 

Demeclocycline Demeclocycline, 7-chloro-4-dimethylamino-l, 4,4a,5,5a,6,11,12a-octahy-dro-3,6,10,12,12a-pentahdroxy-l,ll-dioxo-2-napthacencarboxamide (32.3.4), is prodnced by a mntant strain of S. aureofaciens, in which the mechanism of transferring methyl gronps is disrapted, and thus demeclocycline or demethylchlorotetracycline differs from chlorotetracycline, oxytetracycline, and tetracycline in the absence of a methyl gronp at Cg of the hydronaphthacene system. As a result, an antibiotic is synthesized that is more resistant to acids and bases in comparison with the methyl homologs [215-221]. 

The tetracyclines are manufactured by fermentation procedures or by chemical modifications of the natural product. Controlled catalytic hydrogenolysis of chlortetracycline, a natural product, selectively removes the 7-chloro atom and produces tetracycline, the most important member of the group. 

Synonyms. Chlormethylencycline A -(Hydroxymethyl)chlor-tetracycline Methylolchlortetracycline. 7-Chloro-A -(hydroxymethyl)tetracycline C23H25C1N209 = 508.9 CAS—1181-54-0... 

TETRACOMPREN see TBX250 TETRACYANONICKELATE(2-) DIPOTASSIUM, HYDRATE see TBW250 TETRACYCLINE CHLORIDE see TBX250 TETRACYCUNE, 7-CHLORO-6-DEMETHYL- see MIJ500... 

Metronidazole (Flagyl), tetracycline, dehydroemetine, and chloro-quine (Aralen) are tissue-acting agents, whereas iodoquinol... 

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. 

Research efforts are currently underway to develop a Q fever vaccine that is safe to administer to anyone, including Q fever-immune individuals. The residue of C burnetii organisms following chloro-form-methanol extraction (CMR vaccine) has been tested for safety in nonimmune volunteers97 and is currently being tested for safety in Q fever-immune individuals. Antibiotic prophylaxis of Q fever has been tested with a tetracycline, as was discussed in the treatment section of this chapter. 

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. 

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