Synthesis Of 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose And Polyhydroxylated Piperidine Alkaloids

This dissertation is presented in two parts. The first part mainly deals with process improvement of the synthesis of 1-O-Acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose; and the second part involves the synthesis of polyhydroxylated piperidine alkaloids including preparation of the key intermediate-polyhydroxylated cyclic nitrone.Medicines of nucleoside and its derivatives are very important types of chemical drugs, and the quantity of this kind of medicines is increasing rapidly. To obtain this kind of drugs, synthetic process of 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose must be studied since it is a key intermediate for nucleosides and its derivatives. With D-ribose as the starting material, We synthesized 1-O-acetyl-2,3,5,-tri-O-benzoyl-β-D-ribofuranose by methylation, benzoylation and acetylization successively. Effects of the ratio of reactants, reaction time and reaction temperature on the yield of the product were studied in detail. The total yield could reach to 68% in three steps by optimizing experimental conditions, and the reactions are robust and of excellent repetition. After improvement, the synthetic process can be performed under milder conditions, and is more environment-friendly. This enables the process to be carried out with lower cost and facilitates industrial production.As an important class of glycosidase inhibitors, polyhydroxylated alkaloids display a range of potential biological activities and pharmaceutical value. Therefore, they have caught wide attention of many biologists and organic chemists. Polyhydroxylated piperidine alkaloids have been known as the most important class of polyhydroxylated alkaloids, and pursued as a hot spot for a long time. Employing D-xylose as the starting materials, we successfully synthesized the key intermediate polyhydroxylated cyclic nitrone 92 via a seven-step process with total yield of 16%, and can be prepared on a hundred-gram scale. Based on this key intermediate, we obtained polyhydroxylated piperidine alkaloids 94 in two steps, i.e., nucleophilic addition of various Grinard reagents with nitrone, followed by catalytic hydrogenation. The biological evaluation of these compounds is undergoing. The establishment of this methodology is of huge significance for the future work in this area. D-xylose...