Chemoenzymatic preparation of novel cyclic imine sugars and rapid biological activity evaluation using electrospray mass spectrometry and kinetic analysis
Chemoenzymatic preparation of novel cyclic imine sugars and rapid biological activity evaluation using electrospray mass spectrometry and kinetic analysis
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DOI：
10.1021/ja971695f
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发表时间：
1997-09-03
影响因子：
15
通讯作者：
Wong, CH
中科院分区：
文献类型：
--
作者：
Takayama, S;Martin, R;Wong, CH
环亚胺糖是通过一种新的化学酶策略制备的，其中叠氮基糖，通过酶促羟醛缩合反应构建，在酸性条件下氢化。发现这些环状亚胺糖是糖加工酶的有效抑制剂，其对于多种糖苷酶具有纳摩尔和微摩尔范围的Ki。与其完全氢化的对应物相比，环状亚胺糖通常显示出对所测试的糖苷酶相当或更好的抑制。由于这些环状亚胺是如此容易获得的，并且由于亚胺是各种环加成、缩合和亲核加成中的关键中间体，因此它们作为用于制备新型亚氨基环醇和衍生物的通用合成中间体是有价值的。这种合成效用的一个实例通过经由三中心、双组分Strecker反应合成氨基-亚氨基环醇24来证明。还描述了一种使用电喷雾质谱法快速筛选糖苷酶抑制剂的新方法，并显示出能够鉴定有效的岩藻糖苷酶抑制剂用于详细的动力学分析。此外，在叠氮基糖的还原胺化以制备五元环亚氨基环醇8中，发现铑与钯或铂催化剂相比显示出上级面选择性。
Cyclic imine sugars were prepared by a novel chemoenzymatic strategy in which azido-sugars, constructed by enzymatic aldol reactions, were hydrogenated under acidic conditions. These cyclic imine sugars were found to be potent inhibitors of glycoprocessing enzymes having K-i's in the nanomolar and micromolar range for a variety of glycosidases. In comparison with their fully hydrogenated counterparts the cyclic imine sugars generally showed comparable or better inhibition against the glycosidases tested. Because these cyclic imines are so readily available and since imines are key intermediates in a variety of cycloadditions, condensations, and nucleophilic additions, they are valuable as versatile synthetic intermediates for the preparation of novel iminocyclitols and derivatives. An example of such synthetic utility is demonstrated by the synthesis of amino-iminocyclitol 24 via a three-center, two-component Strecker reaction. A novel method for rapidly screening glycosidase inhibitors using electrospray mass spectrometry is also described and shown to be capable of identifying potent fucosidase inhibitors for detailed kinetic analysis. Also, in the reductive amination of azido-sugars for the preparation of the five-membered ring iminocyclitol 8, rhodium was found to exhibit superior face selectivity when compared to palladium or platinum catalysts.