The Synthesis, Structural Analysis And Biological Activity Of Novel C-Disaccharides

C-Saccharides are class of important mimics of the naturally occurring O-saccharides in which the interglycosidic oxygen has been replaced by carbon. The C-saccharides commonly exhibited highly glycosidases inhibitory activity and could be used as the leads for R& D of new carbohydrate-based glycosidase inhibitors and related new drug due to their good resistance to the acidic and enzymatic hydrolysis. Especially, C-disaccharides, one of the simplest C-oligosaccharides, have been readily used in the design of developing new glycosidase inhibitors owning to their relatively simple structure and high biological activity. In recent years, great attention has been attracted on the design and synthesis of novel C-disaccharides for investigating their biological activity, the relationship of structure-activity, and for developing new carbohydrate-based glycosidase inhibitors and related new drugs.On the basis of the recent progress of the synthesis and biological activity of C-disaccharides, and considering the general biological activity of heterocyclic compounds, in this dissertation, series of novel C-disaccharides linked by a spiro-isoxazoline or by an isoxazoline have been designed and stereoselectively synthesized, and a series of new C-azadisaccharides and five-membered azasugars were conveniently prepared using the isoxazoline linked C-disaccharides and D-glucose as the starting materials, respectively. The biological activities of some of the synthesized new compounds against the glycosidases, antiviral and antitumor have been preliminarily evaluated.1. A series of novel spiro-isoxazoline C-disaccharides were efficiently synthesized by the stereospecific 1,3-dipolar cycloaddition reaction of benzyl protected exo-glycals to sugar nitrile oxides, followed by catalytic hydrogenation deprotection. The synthesis provided the a-isomer in high yields exclusively.2. A series of novel isoxazoline-linked C-disaccharides were conveniently prepared by the stereoselective 1,3-dipolar cycloaddition reaction of benzyl protected allyl-C-glycosides to sugar nitrile oxides, followed by catalytic deprotection with Pd(OH)2/C. The cycloaddition reaction underwent regiospectifically. 3. Furthermore, using the isoxazoline-linked C-disaccharides as the key intermediates, a series of new aza-C-disaccharides have been conveniently synthesized via the reductive cleavage of the isoxazoline ring, followed by condensation-recyclization of the aldehyde and the in situ generated amine groups, and then hydrogenation, providing a practically new access to aza-C-disaccharides.4. A practical and efficient synthesis of 1,4-dideoxy-1,4-imino-D-arabinol and its partially protected derivatives has been developed via the key intermediate with a norbornane-like structure using D-glucose as a starting material.5. The biological activities of the synthesized novel C-disaccharides against the glycosidases (a-amylase, a-glucosidase andβ-glucosidase) and HIV and BVDV have been preliminarily evaluated. Some of the compounds showed a certain biological activity, which would be helpful for the further design of such compounds.