6-Deoxytetracycline

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. 

The iacreased chemical stabiUty of the 6-deoxytetracyclines allows chemical modification with retention of biological activity electrophilic substitutions have been carried out at C-7 and C-9 under strongly acidic conditions (46—53). Reactions of 6-deoxy-6-demethyltetracycline [808-26-4] (16), C21H22N2O7, with electrophiles, such as nitrate ion (49), bromomium ion (46,47) (from N-bromosuccinimide), or N-hydroxymethylphthalimide (53), yielded 7-substituted tetracyclines. In the case of the nitration reaction, both the 7- and 9-nitro isomers (17, X = NO2, Y = H) and (17, X = H, Y = NO2) were obtained. 

In a synthesis of minocycline, interesting use was made of a reductive alkylation of a nitro function, accompanied by loss of a diazonium group. The sequence provides a clever way of utilizing the unwanted 9-nitro isomer that arises from nitration of 6-demethyl-6-deoxytetracycline (//). When di-azotization was complete, urea and 40% aqueous formaldehyde were added, and the entire solution was mixed with 10% palladium-on-carbon and reduced under hydrogen. No further use of this combined reaction seems to have been made. 

Reductive Methyiation of 7-IN,N -Dicarbobenzyloxyhydrazino)-6-Demethyl-6-Deoxytetra-cycline to 7-Dimetbylamino-6-Demetbyl-6-Deoxytetracycline A solution of 100 mg of 7-(N,N -dicarbobenzyloxyhydrazino)-6-demethyl-6-deoxytetracycline in 2.6 ml of methanol,... 

Fig. 5.8 Structures of two tetracycline analogues, which are members of the new glycylcycline group of antibiotics A, yV,A -dimethylglycylamido-6-demethyl-6-deoxytetracycline B, N,N-dimethylglycylamidominocycline.

Demethyl-6-deoxytetracycline, 24 600 6-Demethylchlortetracycline, 24 592 Demigras coal grade (France), 6 713t Deminerahzation water softening method, 26 122, 123... 

Deoxytetracyclines, 24 595, 596 Deoxythymidylic acid (dTMP), folic acid and, 25 801... 

Interesting photolyses have been reported in the tetracycline series.112 Irradiation of the hydrochloride of 6-demethyl-6-deoxytetracycline-7-diazonium sulfate in acetic acid gives 6-demethyl-6-deoxytetracycline (A). The reaction also gives 7-bromo-, 7-fluoro, and 7-acetoxy-6-de-... 

For almost half a century, tetracycline (68) has been well-known as a major antibiotic from the viewpoint of its unique structural features as well as antibacterial activities 24). The total synthesis of tetracycline families was initiated by Woodward s 6-demethyl-6-deoxytetracycline synthesis in 1962 (25), followed by Muxfeldt s terramycin synthesis in 1968 (26), and culminated by Stork s 12a-deoxytetracycline synthesis in 1996 (27). However, all these syntheses have been accomplished only in racemic forms. The total synthesis of... 

S. B., Inhibition of the tetracycline efflux antiport protein by 13-thio-substituted 5-hy-droxy-6-deoxytetracycline, J. Med. Chem... 36,. 370, 199.3. 

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... 

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