Studies On The Synthesis Of 7-Dimethyl-amino-6-demethyl-6-deoxytetracycline

This thesis focuses on the synthesis of 7-dimethylamino-6-demethyl-6-deoxy -tetracycline(Minocycline),which is divided into two parts.Part one studies on the synthesis of 7-Dimethyl-amino-6-demethyl-6-deoxytetracycline. 7-dimethylamino-6-demethyl-6-deoxy-tetracycline(Minocycline) is a semisynthetic second-generation tetracyclines and is greatest curative effect compound in the tetracyclines family.The key intermediate,6-demethyl-6-deoxytetracycline was obtained normally by catalytic hydrogenation of demeclocycline.under high pressure. Herein,a facile approach to 6-demethyl-6-deoxytetracycline is achieved by a two-step hydrogenation of demeclocycline,removing 7-chloride and 6-hydroxy with Palladium-on-carbon catalyst respectively.This approach is facile,economy way with high yield,and can be used for industrial purpose.After obtained the key intermediate 6-Demethyl-6-deoxytetracycline,we try to synthesize 7-dimethylamino-6-demethyl-6-deoxy-tetracycline.Studied some of the routes,we decide to react with dibenzyl azodiformate,and the product 7-[1, 2-bis-(carbobenzyloxy)hydrazine]-6-demethyl-6-deoxy-tetracycline thus obtained, then it in methanol,aqueous formaldehyde solution and Pdlladium-on-carbon catalyst was hydrogenated to form 7-dimethylamino-6-demethyl-6-deoxy- tetracycline.Part two reviews on the researching progress of tetracycline-type antibiotics which including 33 references.Since the extensive use of tetracyclines in animals and humans resulted in the emergence of widespread bacteria resistance,the development of tetracyclines is limited.Succeeded in synthesis third-generation tetracyclines,the old antibiotics has a new hope of development.In this paper,we will completely discuss the phylogeny of tetracyclines and some of the tetracyclines still be used now.We will also completely introduce the Tigecycline a new pharmaceutical approved by US FDA in 2005.The author also provides some advice on the structure modification.