Synthesis of Biologically Active Compounds via Novel Synthetic Reactions Using Lewis Acids

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Based on the investigation of novel synthetic reactions using Lewis acids, we examined the reactions between 2,2-dialkoxycyclopropanecarboxylic esters and carbonyl compounds. The reaction with aldehydes gave cis-3,4-substituted-gamma-lactones with high selectivities in the presence of titanium tetrabromide or tin tetrabromide as a Lewis acid.Furthermore, the reaction between s ymmetric ketones and 3-mono-substituted cyclopropanes gave cis-2,3-substituted-gamma-lactones in high yields with high stereoselectivities.Next, we tried to control tree continuous asymmetric centers in a lactonering. As a result, we found that 2,3-cis, 3,4-trans-tri-substituted gamma-lactones were synthesized with high selectivities by using zirconium tetrachloride as an activator.Using this methodology, the synthesis of dihydropertusaric acid, isolated from a lichen, was performed.However, the stereochemical assignment of the naturally occurring lactone was found to be incorrect. Namely the natural compound has 2,3-trans, 3,4-cis configuration, which is not a suitable stereoisomer for the present reaction. Then, we could not synthesize a natural product, but established a simple and stereoselective route to unnatural dihydropertusaric acid and a method for the optical resolution of its racemate. However, the lactones as well as its synthetic intermediates indicated less bioactivity, such as antifungal activity, than we anticipated.Furthermore, we tried the reactions mediated by divalent germanium species and found that it could be utilized in the Barbier type reaction.Namely, allylgermanium (IV) reagents, generated in situ from germanium (II) iodide and allylic halides, reacted with carbonyl compounds to give homoallylic alcohols.