Tetracycline semisynthetic

The isolation of the 6-deoxytetracyclines (44) led to other chemical modifications of (1). 6P-Deoxytetracycline [5614-03-9] (13), prepared by catalytic hydrogenolysis of tetracycline (1), resulting ia an iaversion (45) of the configuration at the C-6 position, but retention of antibacterial activity. Catalytic reduction (7,8) of the 6-methylene derivative (14) yields both the 6a-methyl (15) and 6P-methyl compound (13). The 6a-isomer (15) is reported (7,45) to be more active than the 6P isomer (13). The a-isomer, doxycycline (6), is an example of a semisynthetic tetracycline that has become commercially useful. 

In the United States, the manufacturers of fermentation-derived tetracyclines (1), (2), and (3) are the Ledede Laboratories, a division of American Cyanamid Co., Charles Pfizer Inc., Bristol Laboratories, and RacheUe Laboratories. There are also several manufacturers abroad. Tetracycline is now sold genetically by many companies. Pfizer s doxycycline (6) and Ledede s minocycline (7), both semisynthetic tetracyclines, are the only members of the group that have increasing sales. Table 1 fists the commercial tetracyclines and the corresponding trade names. 

Doxycycline is a semisynthetic, tetracycline, antibiotic drug. Doxycycline hyclate (doxycycline hydrochloride hemiethanolate hemihydrate) injection solutions (100mg/5mL) may be administered by slow IV injection or by IV infusion (maximum four hours). Reconstituted solutions, in either 0.9% sodium chloride injection or 5% dextrose injection, are stable for 48 hours under fluorescent lamps (Product Information Sheet, Vibramycin , 1995). 

The stereochemistry uf the tetracyclines is very complex. Carbon atoms 4. 4a.. S.. Na. 6. and 12a arc potentially chiral, depending on substitution. Oxytctracyclinc and doxycyclinc. each with a Sa-hydroxyl substituent, have six asymmetric centers the others, lacking chirality at C-. >. have only five. Determination of the complete, absolute stcreochemi.stry of the tetracyclines w.as a difficult problem. Detailed x-ray diffraction analysis c.siablished the stereochemical formula shown in Table 10-6 as the orientations found in the natural and semisynthetic tetracyclines. Tlic.se studies also confirmed that conjugated systems exist in the structure from C-10 through C-12 and from C-1 through C-.T and that the formula represents only one uf. several canonical forms exi.st-ing in those portions of the molecule. 

Clomipramine hydrochloride clomipramine, clomocycline [ban, inn] is a semisynthetic (tetracycline) ANTIBIOTIC. It can be used clinically as a broad-spectrum ANTIBACTERIAL. 

Without doubt, the most exciting development in the chemotherapeutics of tetracyclines over the last decade has been the synthesis of the class of semisynthetic tetracycline... 

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