Study On Synthesis And Application Of Organosilyl Protective Agents

Organosilyl Protective Agents(OSPA) are widely used in organic synthesis especially in syntheses of drugs for most of them can be get easily , have a steady property , easy to use and can be get rid off in very mild conditions. And in most of these cases, OSPA can protect/ deprotect functional groups selectively. It is fair to say that, to-date, in any synthesis of reasonable complexity, the use of one kind or another OSPA is unavoidable.It is has become a novel method for improving the process and enhancing the quality of the products in syntheses of drugs. For examples, OSPA are widely used in the syntheses including Semi- synthesis and total synthesis of prostaglandins, 7-ADCA which is a inter- mediate of cephalosporin, Taxol which is a new anticancer drug and Acyclovir-a novel antivirus drug.Three sterically hindered OSPA namely tert-butyldimethchlorosilane(â… ), phenyldimeth- chlorosilane(â…¡) , tert-butyldiphenlychlorosilane(â…¢) are synthesized through Grignard reactions. And the factors which can affect the reactions such as the time of the reaction, the temperature of the reaction, the catalyst and the solvents used in this reaction are studied by the numbers. And than find out the best conditions of these reactions. We also discussed the catalytic mechanism of the reaction for the first time. Furthermore, through the study we find out that:(1)Using CuCN as a catalyst also can get a good yield in such a reaction. CuCN is not dissolve in water, so it is less toxic than NaCN which is traditionally used as one of the catalysts in this kind of reactions. Using CuCN as a catalyst also will not get a offensive odor otherwise it will do when using a SCN group-containing compound as a catalyst . Of course a SCN group-containing compound is also toxic. Therefore CuCN is a comparatively better catalyst than others.(2)In some certain cases it is also can get a good yield by using aether as a solvent. Though the yield is not as high as using THF as a solvent, but it will also can gain a great economic benefit when this carried out in industrialized producing.In the last part of this thesis, in order to recognize the effect of these OSPA as protective agents, we synthesized Simvastatin from Lavastatin by using OSPA as the protective agents of hydroxy. The study indicates that the three OSPA all can protect hydroxy efficiently.