25 Martinellaアルカロイドの不斉全合成(口頭発表の部)

概要

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Due to the novel hexahydropyrrolo[3,2-c]quinoline nucleus as well as their potential use in medicinal chemistry, martinelline (1) and martinellic acid (2), isolated from the root bark of the tropical plant Martinella iquitosensis, have spurred intense efforts to synthesize them. Although there have been reported several total syntheses, the issue on the elucidation of the absolute configurations of 1 and 2 is still the subject of serious arguments. In addition, there have been reported few methodologies that allow facile construction of the tricyclic core in an enantiocontrolled manner. Herein, we describe the first asymmetric total synthesis of (-)-martinelline (1) and the second total synthesis of (-)-martinellic acid (2) based on the highly efficient Lewis base-promoted intramolecular Mukaiyama-Mannich/hemiaminalization reaction using imine 18. Unexpectedly, a comparison of their specific rotations suggested that the reported natural Martinella alkaloids are nearly racemic or mixtures of two enantiomers. To determine which of the two enantiomers confers biological activities, both enantiomers were also synthesized. Evaluation of the GPCR antagonist activity toward H_1-hiatamine receptors on human astrocytoma 1321N1 cells revealed that only (-)-(3aS,4S,9bS)-martinelline (1) exhibits GPCR antagonist activity.
天然有機化合物討論会の論文
2007-08-24