Synthesis of 7-dimethylamino-6-demethyl-6-deoxytetracycline (minocycline) via 9-nitro-6-demethyl-6-deoxytetracycline

Abstract

remove thiophenol and then extracted with Claisen'a alkali (three 100-ml portions). The latter extracts were diluted with water, neutralized with carbon dioxide, and then extracted with hexane. The combined hexane extracts were dried and concentrated to give 2.68 g (91%) of a 43:57 mixture of 8(11)and 8-.An analytically pure sample was obtained by elution from silver nitrate-silica gel: nmr (CDC13) 9.12 (t,

Targeting Antibiotic Resistance

“…Chlortetracycline ( 20 ), the oldest member of this class, was discovered in 1945 and first used clinically in 1948 (Figure 16). 89 Since then, only three other naturally occurring tetracyclines have been discovered (tetracycline ( 21 ),90 oxytetracycline ( 22 )91 and demethylchlortetracycline ( 23 )92), while countless others have been derived semisynthetically, including doxycycline ( 24 )93 and minocycline ( 25 ) 94. Tetracyclines are easily recognizable by their four highly oxygenated fused rings and they show favorable antimicrobial properties along with an absence of major side effects, which has led to their extensive use in both human and animal infections.…”

Tumor Necrosis Factor-Induced Cerebral Insulin Resistance in Alzheimer's Disease Links Numerous Treatment Rationales

“…Minocycline. Minocycline is a particularly broadspectrum oral tetracycline that was synthesized from a naturally occurring antibiotic decades ago (Church et al, 1971). Being the most lipid-soluble of this class of drug, it enters the brain more readily than the rest.…”

Chemical Modification of the Tetracyclines

“…Exploitation of the 9-nitro group for minocycline synthesis thus gave a superior total yield of this compound (CHURCH et al 1971). Considerably improved minocycline yields can be attained, however, by a different reaction sequence.…”

“…Considerably improved minocycline yields can be attained, however, by a different reaction sequence. If 6-demethyl-6-deoxytetracycline (98) is treated with tert-butanol in methanesulfonic acid, then almost exclusively the 9-tert-butyl-substituted compound is obtained (CHURCH et al 1971;BERNARDI et al 1975b). The tert-butyl group in the 9 position is an excellent protecting group which can be easily removed in anhy-drous HF.…”