Chemoenzymatic Synthesis of 7-Deaza Cyclic Adenosine 5'-Diphosphate Ribose Analogues, Membrane-Permeant Modulators of Intracellular Calcium Release

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• 作者：Bo Zhang ; Victoria C. Bailey ; Barry V. L. Potter
• 刊名：Journal of Organic Chemistry
• 出版年：2008
• 出版时间：March 7, 2008
• 年：2008
• 卷：73
• 期：5
• 页码：1693 - 1703
• 全文大小：209K
• 年卷期：v.73,no.5(March 7, 2008)
• ISSN：1520-6904

文摘

An optimized synthetic route to 7-deaza-8-bromo-cyclic adenosine 5'-diphosphate ribose (7-deaza-8-bromo-cADPR 3), an established cell-permeant, hydrolysis-resistant cyclic adenosine 5'-diphosphate ribose(cADPR) antagonist, is presented. Using NMR analysis, we found that 3 adopted a C-2' endo conformationin the N9-linked ribose and a syn conformation about the N9-glycosyl linkage, which are similar to thatof cADPR. The synthetic route was also employed to produce 7-deaza-2'-deoxy-cADPR 4, a potentialcell-permeant cADPR analogue. 3 and 4 were more stable to chemical hydrolysis, consistent with theobservation that 7-deaza-cADPR analogues are more stable than their parent adenosine derivatives. 3was also found to be stable to enzyme-mediated hydrolysis using CD38 ectoenzyme.