10.1039/b207936d
The research focuses on the extension of the "ring switch" approach to the synthesis of glutamate antagonists, specifically utilizing δ-lactam urethanes. The study successfully employed three different types of δ-lactam urethane aldehydes (17, 26, and 59) in the synthesis process, manipulating diastereoisomeric ratios through the use of a hindered proton source to obtain homochiral products with two chiral centers. Although the δ-lactam urethane system was less versatile compared to pyroglutamate or β-lactam urethanes, the research managed to prepare a variety of glutamate antagonist homologues. The experiments involved the synthesis of compounds that mimic glutamate, the fast excitatory receptor in the brain, and are potentially useful in treating illnesses such as persistent pain, Alzheimer’s disease, epilepsy, and ischaemia. The methodology, referred to as a "ring switching" reaction, allows for the economical preparation of a large variety of homochiral compounds. The analyses used in the study included various spectroscopic techniques and chromatography to confirm the structures and purities of the synthesized compounds.
10.1016/S0040-4039(03)00563-X
The study details the enantiospecific total synthesis of the indolizidine alkaloid (+)-ipalbidine, a nonaddictive analgesic with additional biological activities. The synthesis starts from (?)-pyroglutamic acid and involves several key steps. Initially, the alcohol derived from pyroglutamic acid methyl ester is converted to a tosylate, which is then reacted with a higher-order cuprate reagent to form an olefinic amide. This amide is condensed with a bromide, prepared from an ester through reduction and bromination steps, to yield a diene. The diene undergoes ozonolysis to form a diketone, which is then subjected to an intramolecular McMurry coupling reaction using low-valent titanium to construct the desired carbon-carbon double bond, yielding the core structure of ipalbidine. The final steps include reduction of the amide function and debenzylation to obtain the natural product. The study also explores an alternative synthetic path involving the elimination of a vic-diol function from a major byproduct of the McMurry coupling. The developed synthetic strategy is noted for its potential applicability to the synthesis of other biologically active alkaloids.
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