Synthetic Studies On Iminosugar Alkaloids Via Cyclic Nitrone

This doctoral dissertation describes the synthetic studies on iminosugar alkaloids via cyclic nitrone, which consists of Radicamines, methyl 6, 7, 8, 11 tetradeoxy-8, 11-imino-D-β-galacto-D-αo?rβ-galacto-thirteenfuranose as a potential new antituber- culosis agent and 2,3-O-isopropylidene-4-O-benzyl-5-deoxy-5-hydroamino-aldehydo- D-mannose as a key intermediate for a potential anti-tumor agent.We choose fore-mentioned iminosugar alkaloids as target molecules. Based on monosaccharides as chiral starting materials, we carry out the preparation of cyclic nitrones as key intermediates by multistep reactions such as protection of hydroxyl group, introduction of nitrogen and intromolecular cyclization. These cyclic nitrones are comprised of pyrrolizidine-configurations such as L-arabinofuranose's analogue, D-galactofuranose's analogue and D-glucofuranose's analogue and piperidine -configurations such as D-mannopyranose's analogue.We accomplished the syntheses of enantiomers of Radicamine A and Radicamine B by building up anti-substitutive pyrrolizidine via the reaction of Aryl Grignard reagents addition to cyclic nitrone. Furthermore, we confirmed the absolute configurations of both to be (2R,3R,4R,5R) which is the same as ones reported recently.The potential new antituberculosis agent and the potential antitumor agent belong to aza-C-disaccharides, which contain monosaccharide linking with cyclic nitrone. We synthesized methyl 2,3-O-bisbenzyl-5-ethynyl-αo?rβ-L-arabinofurano -side and 1,2-O-isopropylidene-3-O-benzyl-6-deoxy-ethynyl-D-glucofuranose from natural sugars by multistep reactions such as protection of hydroxyl group, oxidation reaction and addition reaction of an ethynyl Grignard reagent to aldehyde.Based on the specific chemical structure (1, 6-β-linked-D-galactofuranose) in the cell wall of Mycobacterium tuberculosis, we built on methyl 6, 7, 8, 11-tetradeoxy-8, 11-imino-D-β-galacto-D-αorβ-galacto-thirteenfuranose as a potential new anti-tuber -culosis agent, which was synthesized via subtly linking methyl 2, 3-O-bisbenzyl- 5-ethynyl-αo?rβ-L-arabinofuranoside with cyclic nitrone.Based on the disaccharide unitα-D-Man-(1-6)-α-D-Man, we built on 6,7,8,12- tetradeoxy-8,12-amino-D-manno-α-D-manno-thirteenfuranose as a potential new anti-tumor agent and finished cyclic nitrone as its key intermediate starting from D-arabinose.All above lay a solid chemical foundation for further research in saccharides in our group.