82(P-83) D-及びL-1-デオキシアザシュガー類の合成とグリコシダーゼ阻害活性(ポスター発表の部)

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Azasugars (or iminosugars) are an important class of glycosidase inhibitors and are arousing great interest as potential therapeutic agents such as antidiabetics, antiobesities, antivirals, and therapeutic agents for some genetic disorders. Miglitol has been approved as the second-generation α-glucosidase inhibitor to treat type 2 diabetes and N-butyl-1-deoxynojirimycin has also been approved for use in patients with type 1 Gaucher disease in 2002 in the European Union and in 2003 in the U.S.A. Recently, it has been demonstrated that competitive inhibitors of lysosomal glycosidases have therapeutic potential for lysosomal storage diseases caused by genetic defects in lysosomal enzymes. 1-Deoxygalactonojirimycin, a powerful inhibitor of lysosomal α-galactosidase, was found to serve as an enhancer of mutant enzyme activity in cells derived from Fabry patients at subinhibitory intracellular concentrations and is currently in preclinical trials for practical use. Newly promising chiral building blocks 3 and 4 in the synthesis of 1-deoxyazasugars were prepared in only four steps from the D-Garner aldehyde 5. In practice, a straightforward synthesis of 1-deoxynojirimycin (DNJ) (1), altro-DNJ (13), manno-DNJ (18), and allo-DNJ (19) using trans-4,5-disubstituted dioxanylpiperidene 3 and a highly stereocontrolled synthesis of galacto-DNJ (2), idono-DNJ (25), and gulo-DNJ (27) using cis-4,5-disubstituted dioxanylpiperidene 4 have been demonstrated. In a similar manner, their L-1-deoxyazasugars were also prepared starting from L-Garner aldehyde. Several abilities of both enantiomers of the prepared seven 1-deoxyazasugars as glycosidase inhibitors were demonstrated.
天然有機化合物討論会の論文
2004-10-01

82(P-83) D-及びL-1-デオキシアザシュガー類の合成とグリコシダーゼ阻害活性(ポスター発表の部)

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