An efficient diastereoselective multi‐step synthesis of bicyclic 1β‐methylcarbapenem antibiotic precursors has been developed, starting from the commercially available 4‐acetoxyazetidin‐2‐one 4. Chiral ruthenium catalysts are used in the hydrogenation step to control the β‐stereochemistry at the 1‐position, and a π‐allylpalladium ring‐closure strategy is used to form the functionalized carbapenem skeleton.
Practical synthesis of 2-ethoxycarbonylimidazole-4-phosphonate (1a) and diethyl imidazole-2,4-dicarboxylate (1b) are described.J. Heterocyclic Chem., 40, 159 (2003).Over the last twenty years, it has been well established that L-glutamate was the major excitatory neurotransmitter in the mammalian central nervous system (CNS) [1]. Glutamate plays an essential role in many physiological CNS functions through the activation of three major types of postsynaptic ionotropic receptors designated according to the non-natural substances that selectively activates them: NMDA (N-Methyl-D-Aspartate), AMPA 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid) and Kainate receptors. In addition, glutamate activates several types of metabotropic receptors signalling through a G-protein coupled [2]. In connection with our program aimed at the development of potent and selective AMPA antagonists as source of potential drugs for cerebral ischemia or epilepsy [3], we needed to develop easy and efficient methods leading to 2-ethoxycarbonylimidazole-4-phosphonate (1a, Scheme 1) and diethyl imidazole-2,4-dicarboxylate (1b, Scheme 2) [4].To our knowledge, few phosphorylated imidazoles were already described. Thus, the imidazol-2-ylphosphonic acids were prepared by direct action of the corresponding N-protected imidazoles with various phosphorus (V) acid chlorides following hydrolysis . Likewise, relatively few 1H-Imidazole-2,4-dicarboxylates have been synthesized to date. Thus, 1b was only prepared via the hydrogenation of diethyl 1-(p-methoxybenzyl)imidazole-2,4-dicarboxylate which was obtained in a two steps synthesis from 2-amino-2-cyano acetate and 1-ethoxycarbonylformimidate in a 25 % overall yield [6]. The corresponding dimethyl imidazole-2,4-dicarboxylate was synthesized by photolysis of methyl (E)-3-(5-methoxycarbonyltetrazol-1-yl) propenoate [7]. 2-Carboxy-4-carbomethoxyimidazole has been obtained by the condensation of ethyl amino-oximinoacetate with methylpropiolate followed by an in situ thermolysis reaction [8]. Finally, diethyl 4-amino-1-(H)imidazole-2,5-dicarboxylate has been prepared from carboxyethoxyformimidate [9].Preparation of 2-Ethoxycarbonylimidazole-4-phosphonate (1a).As outlined in Scheme 1 (Pathway A), our fist attempt was based on the simple 5-lithiation reaction [10]
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