The Total Synthesis Of Tubercidin And Its Analogues

Many pyrrolo[2,3-d]pyridine compounds have shown the very significant physiological and biological activity. And pyrrolo[2,3-d]pyridine nucleoside compounds are favored by many biologists, medicinal chemists and organic chemists, As a new type of potential drugs for antibacterial, antiviral, anticancer and immunosuppressive, etc. Tubercidin and Toyocamycin, as one of the representative pyrrolo[2,3-d]pyridine nucleoside compounds, have extensive and excellent biological activity but bad pharmaceutical selectivity and highly toxic effect, so it is very urgent and necessary to research develop its analogues with better selectivity and less toxicity.In order to reduce the side effects and encrease pharmaceutical selectivity, medicinal chemists usually use drug carrier to carry some effective drugs to the target cells or tissue. With development of carbohydrate chemistry, carbohydrates, one of the information molecular in organisms, plays an important role in many biological identification process. So carbohydrates are often cited as a very effective drug carrier.Given mechanism of targeting drugs, This dissertation is focusing on design and synthesis of two natural products with glucose transporter: Tubercidin-5’-O-a-D-glucose and Toyocamycin-5’-O-a-D-glucose. This two7-deazapurine nucleoside extracted from cultured cyanophytes have strong cytotoxicity and antimycotic activity.This dissertation aims to find the optimal reaction conditions of synthesis of nucleosides by developing Vorburggen glycosylation and investigate possible mechanism for the Vorburggen glycosylation and O-glycosylation reaction in the process of synthesis of Tubercidin, Tubercidin analogues, Tubercidin-5’-O-a-D-glucose, and Toyocamycin-5’-O-a-D-glucose and1’-deoxidize-D-ribose-2’-isonucleoside.