10.3987/COM-07-S(U)36
The research focuses on the total synthesis of (±)-Komaroviquinone, a natural product with significant trypanocidal activity against Chagas' disease. The synthesis is achieved in 22 steps, starting from 3,4,5-trimethoxybenzoic acid. Key transformations include the construction of a cycloheptane ring via a Friedel–Crafts cyclialkylation, a regiospecific benzylic oxidation, a conformationally controlled introduction of the C(10) hydroxyl group, and intramolecular hemi-acetal formation. The study leverages various reagents and conditions, such as NBS for electrophilic bromination, m-CPBA for epoxidation, LAH for reduction, and PCC or CrO3 for oxidations. The research also explores the oxidation of benzylic positions in electron-rich arenes and the challenges in eliminating secondary alcohols to form trisubstituted double bonds. The final product's structure was confirmed through 1H and 13C NMR, IR, and MS spectra, which matched those of the natural compound.
10.1021/op400113a
The study details an enhanced method for synthesizing trimethobenzamide hydrochloride (Ia), an antiemetic agent used to treat nausea. The researchers aimed to develop a process that avoids common impurities formed during the coupling of 4-(2-dimethylaminoethoxy)benzyl amine (IV) with 3,4,5-trimethoxy benzoic acid (V). They experimented with various coupling reagents and found that N,N'-carbonyldiimidazole (CDI) provided the best results. By optimizing the mole equivalents of CDI, they achieved a high-purity product without the need for column chromatography or repeated crystallization. The final process involved reacting 3,4,5-trimethoxy benzoic acid with CDI to form an intermediate, which was then coupled with 4-(2-dimethylaminoethoxy)benzyl amine in the presence of potassium carbonate, yielding trimethobenzamide hydrochloride with a purity of =99.5% and a satisfactory yield.
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