A versatile access to calystegine analogues as potential glycosidases inhibitors.
A versatile access to calystegine analogues as potential glycosidases inhibitors.
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作为潜在的糖苷酶抑制剂的一种多功能途径。
DOI：
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发表时间：
2009
影响因子：
3.6
通讯作者：
S. Sabharwal
中科院分区：
文献类型：
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作者：
K. Kaliappan;P. Das;Sanjay T. Chavan;S. Sabharwal
8-氮杂双环[3.2.1]辛烷是一种有效的歧化反应策略和硝酮化学相结合的方法，可作为合成多种催化甜菊碱类化合物的前体。这一合成策略依赖于甘露糖衍生的硝酮通过各种格氏试剂的高度立体选择性的亲核加成来获得烯烃的同步取向，然后顺利地进行闭环歧化(RCM)来提供这一框架。这些RCM产物18和20已经成功地作为高级前体，通过合成二羟基化或氢化，然后全局去保护，合成了许多催化甜氨酸类似物(27，36，38，40，43和44)。有趣的是，化合物36和40对α-甘露糖苷酶和N-乙酰-β-D-氨基葡萄糖苷酶均表现出显著的非竞争性抑制作用。
An efficient metathetic strategy and nitrone chemistry have been suitably tethered to construct 8-azabicyclo[3.2.1]octanes as versatile precursors for the synthesis of several calystegine analogues. This synthetic strategy relies on the ability of mannose-derived nitrone to undergo a highly stereoselective nucleophilic addition of various Grignard reagents to access syn orientation of alkenes, which then smoothly undergo ring-closing metathesis (RCM) to provide this framework. These RCM products 18 and 20 have been successfully used as advance precursors to synthesize many calystegine analogues (27, 36, 38, 40, 43, and 44) either by syn-dihydroxylation or by hydrogenation and followed by global deprotection. Interestingly, both compounds 36 and 40 exhibited significant noncompetitive inhibition against alpha-mannosidase and N-acetyl-beta-D-glucosaminidase.