Design, Synthesis Of Phthalimide Derivatives And Improved Synthesis Of R Or S-Thalidomide

Recent medical studies indicated that tumor genesis, growing and metastasis were depended on angiogenesis, in addition, the rate that angiogenesis formed in tumor was faster than that of the normal tissues by 50-200 times. Meanshile, the angiogenesis in adult people has been ceased. So inhibition angiogenesis became an effective therapy which was called the fifth therapies of cancer. It became a new research hotspot to design and synthesize novel drugs target to the antiangiogenesis. The synthesis of thalidomide and it's derivatives are the important issues all along because thalidomide shows strong biological activities to antiangiogenesis. This paper presents the advances of thalidomide and it's derivatives. The author improved the synthetic process of thalidomide ultilizing the latest advances and kept the same optical rotation with materials in high yields under mild conditions. We compared all kinds of synthetic routes then chose the Nefken's reagent without using the acute base to insure fixing the optical rotation of intermediates and target compounds. So it is possible to design and synthesis chiral compounds in good yields and optimize process of thalidomide preparation without racemization which made it reality to produce the R-or S-thalidomide in scale.Latest achivements showed that bad solubility and phannacokinetic mostly resulted in the low absorption and bioavailability. So based on the synthetic studies of thalidomide, author further researched the synthesis of derivatives, effective groups of RGD, salifying to enhance solubility, more pharmacophores, then prepared a novel series of phthalimide derivatives with excellent solubility and phannacokinetic according to the structure of thalidomide, aim to afford the candidates screening of prodrugs. The derivatives were expected to possess stronger bioavailability. Through this research a new decorative strategy of thalidomide was eager to carry out that the phthalimide derivatives were synthesized base on the auxiliary of cyclic anhydride without racemization.