Protection And Deprotection Of Reactions Of Sugars And Synthesis Of Bioactive Compounds From Sugars, Design And Synthesis Of Sialyltransferase Inhibitors

This thesis consists of three sections as below:I. Efficient Formation and Cleavage of Benzylidene Acetals by NaHSO₄.SiO₂Protecting-group manipulation is still an essential element in preparative carbohydrate and oligosaccharide synthesis. Therefore, the development of mild and efficient conversion conditions both for the formation and for the cleavage of protive groups is still in demand. In this section, we have developed an efficient and facile method for both the formation and the cleavage of benzylidene acetals using NaHSO₄·SiO₂ as a heterogeneous catalyst. The advantage is good chemoselectity with high yield.II. Improved Synthesis of Phytosphingosine and Dihydrosphingosine from galactalCarbohydrates constitute the most abundant group of natural products, and play important roles in a variety of biological process. Furthermore, monosaccharides are chiral polyhydroxyl carbonyl compounds, and can serve as a chiral synthon for synthesis of other chiral compounds with different functions. In this work, we synthesized phytosphingosine and dihydrosphingosine derivatives via four or five steps in 66-72% yield, respectively.III. Design and synthesis of sialyltransferase inhibitors based on transition stateSialylation at the non-reducing end of glycoconjugates is an important biological event in a variety of cellular recognitions, virus infection, tumor metastasis and immune responses, which is mediated by a family of enzymes known as sialyltransferases. Since the inhibitors with sialyltransferases specificity could regulate sialyltranferase activities in cells, subsequently affect the structure of sialyl-containing oligosaccharide, they could therefore be useful in further elucidating the biological functions of sialyl residues as well as future therapeutic agents as new potent antiflammatory immunosuppressive and antitumor metastasis. Sialyltransferases and CMP-Neu5Ac as research targets, combining with the proposed mechanism of sialyltransferase-catalyzed reaction, this section is focused on design and synthesis of sialyltransferase inhibitors based on transition state.For the cyclopentane ring, the more stable conformer is the half-chair. So the highly substituted cyclopentane with a phosphonate group was chosen as framework and then coupled with CMP, which is our target molecule. Under guide of SAR (structure and activity relation), seven target molecules was designed and synthesized. Ribose as starting material, through several key reactions including ozonylsis, Wittig reaction, Dieckmann reaction, and elimation, we synthesized several cylcopentanes with highly substituted groups. Then these key intermediates were transformed toα-hydroxylphosphonate compounds. The target molecules were furnished by couplingα-hydroxylphosphonate with phosphite followed by oxidation and deprotection.We will estimate activity of these compounds and futher study SAR of these compounds. We wish we can find new, good inhibitors of sialyltransferase and serve as prodrug.4. Synthesis of thiosugar and its applicationThiosugars are carbohydrate analogues in which one or more oxygen atoms are substituted by a sulfur atom both in the pyranoside and furanoside structures. In recent years, these compounds have attracted considerable interest from chemists because of their biological activity. In this section, we synthesized thiosugars from diol through "one-pot and two steps" with good yields. Furthermore, one of thiosugars was transformed to polyoxgenated cyclopentene by Ramberg- Bl(a|¨)cklund reaction.