Polyhydroxylated aminocyclitols和 indolizidines的衍生物，因其具備和醣類相似的結構，所以和醣水解酵素之間擁有奇特和有趣的作用，因此有潛力可以發展成為醣水解酵素抑制劑。我們以便宜且具對掌性質之D-(-)-quinic acid為起始物，成功的合成出不對稱的tetrahydroxy aminocyclitols。使用trans-4-hydroxy-L-proline作為起始物再搭配RCM(ring-closing metathesis)的合成策略成功的合成dihydroxylated indolizidines。我們希望合成出來的polyhydroxylated aminocyclitols和indolizidines的衍生物，能有好的生物活性。 Naturally occurring polyhydroxylated aminosugars are considered to be potential glycosidase inhibitors. These glycosidase inhibitors possess potential in the treatment of cancers, HIV, diabetes and metabolic disorders. Especially in diabetes, it is estimated that the number of diabetes patients is expectd to rise from the current estimated of 150 million to 220 million in 2010.
Polyhydroxylated aminosugars have been known as glycosidase inhibitors. They display the same stereochemistry as the corresponding hexoses, exceptor nitrogen atom replacing the original oxygen. Herein we report a stereoselective synthesis of tetrahydroxylated aminocyclitols starting from D-(-)-quinic acid. Subsequent ring-closing metathesis (RCM) was employed to synthesize dihydroxylated indolizidines from trans-4-hydroxy-L-proline.
The resulting tetra-hydroxylated aminocyclitols and di-hydroxylated indolizidines are glycosidase inhibitors.
