Synthesis, receptor binding and activity of iso and azakainoids

被引：12

作者：

Wang, Wentian ^{[1
]}

Simovic, Dragan D. ^{[1
]}

Di, Mingping ^{[1
]}

Fieber, Lynne ^{[2
]}

Rein, Kathleen S. ^{[1
]}

机构：

[1] Florida Int Univ, Dept Chem & Biochem, Miami, FL 33199 USA

[2] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, Miami, FL 33149 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 07期

关键词：

Kainoids; Synthesis; Glutamate receptor; Receptor binding; 1,3-DIPOLAR CYCLOADDITIONS; ENANTIOSELECTIVE SYNTHESIS; DIPOLAR CYCLOADDITION; ASYMMETRIC-SYNTHESIS; GLUTAMATE RECEPTORS; KAINATE; APLYSIA; ACIDS; MECHANISMS; CPAA;

D O I：

10.1016/j.bmcl.2013.02.046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two syntheses for the production of an unsubstituted azakainoid are described. The 1,3-dipolar cycloaddition of diazomethane with trans-dibenzyl glutaconate yields a 1-pyrazoline, which may be reduced directly to the pyrazolidine. An unexpected trans-cis isomerization is observed during Hg/Al reduction of the 1-pyrazoline N=N bond. Alternatively, when TMS diazomethane is used as the dipole, the resulting 2-pyrazoline obtained after desilylation may be reduced with NaCNBH3 to provide the trans azakainate analog exclusively. The synthesis of an unsubstituted isokainoid via Michael addition is also described. Glutamate receptor binding assays revealed that the azakaniod has a moderate affinity for unspecified glutamate receptors. Membrane depolarization of Aplysia neurons upon application of the azakainoid demonstrates that it is an ionotropic glutamate receptor agonist.. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：1949 / 1952

页数：4

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