荒井 秀

Cyano (CN) groups are equivalent to carbonyl as well as amino- and hydroxymethyl groups. Therefore, their catalytic introduction under metal catalysis is an important issue in synthetic organic chemistry. Ni-catalyzed hydrocyanation is one of the most well-investigated, powerful tools for installing a CN group. However, it is still difficult to control chemo- and regioselectivity. In this review, the author uses allenes to enable regio-, stereo-, and face-selective transformations to natural product synthesis and axial chirality transfer.

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.

We have already successeded the formal total synthesis of (±)-manzamine A (1) via key intermediate (3). For asymmetric total synthesis of (+)-manzamine A, we established effective asymmetric synthesis to key intermediate (+)-3 (Scheme 6). Catalytic allylation of 20 using only 0.15mol% [PdCl(allyl)]_2 and 0.36mol% ligand 23 gave 21 in 83% yield with 81% ee. Intramolecular Michael reaction of 28 which has β-TIPS ether proceeded with high diastereoselectivity. Therefore, optically pure (+)-3 was synthesized from ethyl 4-oxopiperidine-3-carboxylate in 12 steps and in 38% over all yield. Further investigation toward the asymmetric total synthesis of (+) manzamine A (1) from (+)-3 will be discussed.

The development of the catalytic asymmetric epoxidation of enones promoted by aqueous H2O2 with chiral quaternary ammonium salts is described. The reaction smoothly proceeded to give α,β-epoxyketones with satisfactory enantioselectivities in both the trans and cis enone systems (up to 92% ee) by use of cinchonine or quinidine derivatives (5 mol%) as phase transfer catalysts. © 2002 Elsevier Science Ltd. All rights reserved.

The development of the catalytic asymmetric Darzens reaction utilizing chloromethyl phenyl sulfone is described. The reaction smoothly proceeded to give α,β-epoxysulfones with satisfactory enantioselectivity (up to 83% ee) using chiral quaternary ammonium salts as the phase transfer catalyst. © 2002 Elsevier Science Ltd. All rights reserved.

The development of the catalytic asymmetric epoxidation of enones promoted by aqueous H2O2 with chiral quaternary ammonium salts is described. The reaction smoothly proceeded to give alpha,beta-epoxyketones with satisfactory enantioselectivities in both the trans and cis enone systems (up to 92% ee) by use of cinchonine or quinidine derivatives (5 mol%) as phase transfer catalysts. (C) 2002 Elsevier Science Ltd. All tights reserved.

The development of the catalytic asymmetric Darzens reaction utilizing chloromethyl phenyl sulfone is described. The reaction smoothly proceeded to give alpha,beta-epoxysulfones with satisfactory enantio selectivity (up to 83% ee) using chiral quaternary ammonium salts as the phase transfer catalyst. (C) 2002 Elsevier Science Ltd. All rights reserved.