Studies On Green Synthesis Of Taxol AB Ring Skelton, Quinolones And Some Other Drugs

Green chemistry is the design, development, and implementation of chemical products and processes to reduce or eliminate the use and generation of substances hazardous to human health and the environment. In this dissertation, several pharmaceutical compounds were investigated under green organic synthesis guidance.Firstly, an effective methodology has been developed leading to the successful synthesis of 8,ll-dimethylene-bicyclo[5.3.1]undecan-2-one. Cationic-alkyne cyclization and base induced fragmentation produced the desired molecule as the sole product. The near quantitative yields in this synthesis suggests that this methodology will be useful in additional synthetic efforts planned in this area.Secondly, the research put forward a new synthetic method of the main ring of quinolones. The key reaction is applying Ethyl N,N-dimethylaminoacrylate, with one pot strategy to accomplish the ring system. (S)-(-)-Ofloxacin and Gatifloxacin were prepared by acylating reaction, followed by coupling with Ethyl N,N-dimethylaminoacrylate, displacement with different amine, cyclization and hydrolysis, finally condesation. The materials were easily obtained, the operation was easily controlled and the final product has high optical purity. Further investigation gave a new synthesis of β -substituted aminoacrylate, and more straight forward synthetic route to the main ring of quinolones.Thirdly, an efficient synthesis of Atovaquone is developed via intensive studies on the radical-based conjugate addition of 2-chloronaphthoquinone through a Hunsdiecker decarboxylation of 4-(4-chlorophenyl)cyclohexane-l-carboxylic acid. The absolute structure of the trans-, cis-isomers of Atovaquone has been confirmed by X-ray diffraction study. The stereoselectivity of the reaction has been further improved from the study of reaction mechanism.Fourthly, an effective methodology has been developed leading to the successsful synthesis of L-Theanine. Protection of commercial available and cheap L-Glutamic acid followed by dehydration produced the key intermediate N-Phthaloyl-l-glutamicanhydride. Ethylamine addition and deprotection of the imteremediate gave the final product L-Theanine. The simplicity and efficiency of this synthesis suggests that this methodology will be useful in additional efforts planned in the application and medicinal usage of L-Theanine.Fifthly, Fexofenadine has been synthesized successfully from the green synthesis of three intermediates 3-butyn-l-ol, ethyl 4-bromo- (a, a -dimethyl)phenylacetate and diphenyl-piperidin-4-methanol with improved coupling and hydrolysis reactions. And a novel synthetic route of Fexofenadine has been further issued, the whole route utilized non-toxic, harmless raw material, catalyst and solvents, complied with the spirit of Green Chemistry.