Five-membered ring analogues of shikimic acid.
Five-membered ring analogues of shikimic acid.
复制标题
莽草酸的五元环类似物。
DOI：
10.1021/jo001121k
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Bartlett,PA
中科院分区：
文献类型：
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作者：
An,M;Toochinda,T;Bartlett,PA
莽草酸和莽草酸-分支酸途径的其他中间体是密集功能化的结构，似乎为骨骼修饰提供了有限的选择。我们设计并合成了环戊烯1和2，以及环戊烯3和4，作为新的缩环莽草酸类似物。酶学研究表明类似物1 − 3确实被莽草酸激酶加工成磷酸1-P、2-P和3-Pas莽草酸-3-磷酸的五元环类似物。特别地，类似物1被酶转化的速率仅比天然底物慢3.5倍，而类似物3与莽草酸激酶结合的表观Km为1.7 mM，而莽草酸为0.14 mM。
Shikimate and other intermediates of the shikimate−chorismate pathway are densely functionalized structures that seem to offer limited options for skeletal modification. We designed and synthesized cyclopentylidenes1and2, as well as cyclopentenes3and4, as novel ring-contracted analogues of shikimic acid. Enzymatic studies showed that analogues1−3are indeed processed by shikimate kinase to give phosphates1-P,2-P, and3-Pas five-membered ring analogues of shikimate-3-phosphate. In particular, analogue1is converted by the enzyme at a rate only 3.5-fold slower than that of the native substrate, while analogue3binds to shikimate kinase with an apparentKmof 1.7 mM, compared to 0.14 mM for shikimate.