Synthesis And SAR Studies Of Benzothiazole Derivatives & Transesterification Of Tabersonine Mediated By Cesium Carbonate

This thesis consists of two parts:(1) Design, Synthesis and SAR Studies of Benzothiazole Derivatives As the Hypoglycemic Action Research; (2) A HighlyEfficient Transesterification of Tabersonine Mediated by Cesium Carbonate.The morbidity and mortality of type 2 diabetes (T2D) has risen year after year due to the improvement of living standards and the change of lifestyle, which has brought great damage to the quality and expectancy of human life. The gluconeogenesis in liver is the main process of endogenous glucose production and plays an important role in the balance of blood glucose. Abnormal activation of gluconeogenesis is one reason of the hyperglycemia in people with type 2 diabetes. In recent years, novel drug development targeting the gluconeogenesis process has drawn great attention of scientists with the expounding of gluconeogenesis process.In this part, SD027 was found through high-throughput screening, which exhibited potent inhibitory activity of gluconeogenesis related mRNA levels in vitro. Three series of SD027 derivatives were designed and synthesized and their inhibitory activity of gluconeogenesis related mRNA levels in vitro were evaluated and their structure-activity relationships were summarized.Tabersonine, one of the largest groups of indole alkaloids, is isolated from the Aspidosperma family. It has an abundant biology origin, such as Amnosia tabemaemontana, Cantharanthus roseus and Voacango Africana Stepf, and displays bioactivity in hypotensive, antitumor, hypoglycemic and diuretic. Given its biological abundance and valuable bioactivity, tabersonine is worthy of further structural modification research.Then we explored the ester exchange reaction of tabersonine, discovering a simple and efficient method of ester exchange reaction mediated by cesium carbonate. And a series of C-16 taberosnine analogues were synthesized through ester exchange reaction.This newly developed method offers several notable advantages, such as short reaction time, simple operation, easy availability and nontoxic nature of the reagent. This method provides the possibility of broadening the carboxylic esters of tabersonine in order to improve the biological activity.