西田 篤司

© 2019 Society of Synthetic Organic Chemistry. All rights reserved. Since a cyano group can be transformed to carboxylic acids, amino- and hydroxymethyl groups as well as aldehydes, its installation, particularly catalytic protocol, has been one of the challenging issues in synthetic chemistry. Hydrocyanation of non-activated C-C multiple bonds has been one of the most powerful methods to install a CN group although selectivity control in products has been major challenge because simple olefin such as styrene derivatives is the only substrate to give higher regioselectivity in HCN addition process. In this review, the authors summarize.

© 2018 Society of Synthetic Organic Chemistry. Lundurines A-D were isolated in 1995 from the Malayan plant Kopsia tenuis, which has been used in folk medicine and is a rich source of biologically active alkaloids. Their intriguing hexacyclic framework includes an unprecedented cyclopropa [b] indole that has only ever been identified in lundurines. While these structural features have been attractive as synthetic targets, the first total synthesis was not reported until 2014. While lundurine B and D exhibit appreciable toxicity toward B16 melanoma cells and also reverse multidrug resistance in vincristine-resistant KB cells, their limited availability has prevented further studies for drug development. Therefore, the synthetic studies for these alkaloids and clarify the mechanism of their biological activity should contribute to medicinal chemistry. This review summarizes recent synthetic efforts in the total synthesis of lundurines and related alkaloids.

© 2017 Elsevier Inc. This review focuses on the total synthesis of lundurines A–C. Their main structural feature is a unique cyclopropa[b]indole core that has been found only in these alkaloids. In addition to this characteristic structure, the biological activity makes them as attractive synthetic targets. However, almost two decades passed from their isolation and structural determination in 1995 to their first total synthesis. The first part of this review summarizes the synthetic approaches to the tri- and tetracyclic ring systems of lundurine as well as an inter- and intramolecular cyclopropanation strategy that gives the cyclopropa[b]indole core. The second part presents a detailed description of four total syntheses that were reported from 2014 to 2016. In addition, the asymmetric total synthesis of the related alkaloids grandilodine C and lapidilectine B is described.

We have established aromatic enamide-ene metathesis to give highly substituted indole derivatives. This is a new method for the preparation of chiral 2-trans-cyclopropyl indoles, which successfully led to our H 4 antagonist candidates. Based on this findings, we also designed and synthesized conformationally restricted analogues and regioisomers of the nonsteroidal anti-inflammatory drug indomethacin. Evaluation of the inhibitory effects of these compounds on COX, P-glycoprotein, and multidrug-resistance indicated that NSAIDS modulation of multidrug resistant P-glycoprotein and multidrug-resistant protein-1 is not associated with COX-1 and COX-2 inhibitory activities.