Synthesis of a New Trihydroxy Piperidine Derivative for Glycosidase Inhibitor from D-(-)-Quinic Acid

• Main Authors: Wei-Shen Kuo, 郭威伸
• Other Authors: Tzenge-Lien Shih
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/86579139954835053864

碩士 === 淡江大學 === 化學學系 === 92 === Recently, the syntheses of glycosidase inhibitors have attracted a great deal of attention in academies and industries. These glycosidase inhibitors possess potential in the treatment of cancers, HIV, diabetes and metabolic disorders.The polyhydroxylated piperidines (called “azasugars” or “iminosugars”) have been known as glycosidase inhibitors. They display the same stereochemical information as common hexoses, but a nitrogen atom replaced the ring oxygen of the corresponding pyranose. Among these azasugars, the representative morecu1es, such as 1-deoxynojirimycin (DNJ) and 1-deoxymannojirimycin (DMJ), are strong inhibitors of glucosidase and mannosidase, respectively. Furthermore, 1,4,5-trideoxy-1,5-imino- D-lyxohexitol was synthesized from 3-deoxy- D-hexose and showed good inhibitory activity against theα-D-glucosidase, β-D- glucosidase andβ-D-galactosidase. Our ongoing project is aiming at the synthesis of various glycosidase inhibitors. Thus we reported a new 2,3-epi trihydroxy piperidine, (2S,4R,5S)-2-hydroxymethyl-piperidine-4,5- diol, which was synthesized in eleven steps starting from D-(-)-quinic acid.In addition, the family of quercitols possessed 16 stereoisomers. Among these isomers, (+)-proto-quercitol was isolated first in 1849 but its synthesis was not complete until 1968 by McCasland. We employed (1R,4R,5R)-triacetoxy-cyclohex-2-ene which was derived from the proper transformation of D-(-)-quinic acid to synthesize (+)-proto-quercitol. With the accomplishment from the above, we synthesize a series of protected chiral (1,4,5)-cyclohex-2-ene triols, which can be used in the syntheses of a variety of quercitols in the future