論文

触媒的不斉Payne型酸化による光学活性N-スルホニルオキサジリジン合成法を開発した。適切な反応条件を設定することで、種々のN-スルホニルアルジミンを基質として、酸化反応が効率的かつ高エナンチオ選択的に進行する。

渦鞭毛藻Karenia brevisが生産するポリエーテル天然物ブレビシンの初の全合成を達成した。

A polycyclic ether bravisn (1) was isolated from the red tide dinoflagellate Karenia brevis, which produces a variety of policyclic ethers such as bervetoxins, brevenal, and a mono cyclic ether amide brevisamide. Its unique structure consists of two fused tricyclic ether ring assemblies bridged by a methylene carbon and a conjugated aldehyde side chain, which is similar to brevenal and breviasmide. Its separated polycyclic ether skeleton in the center of the molecule is unusual in the marine polycyclic ethers. Interestingly, even though its skeletal structure is divided into two tricyclic ether units by the methylene, brevisin inhibits the binding of tritiated 42-dihydrobrevetoxin B (PbTx-3) to the voltage sensitive sodium channels (VSSC). In order to confirm its aberrant chemical structure, elucidate its interation was essential. Here the total synthesis of brevisin based on highly convergent strategy using Suzuki-Miyaura cross coupling and aldol reaction as the key reactions was achieved in 29 steps (the longest linear sequence), and the datails will be reported in this presentation.

渦鞭毛藻Karenia brevisより単離された単環性エーテルアミド天然物ブレビサミドの合成を行い、合成標品の生物活性を評価した。

光学活性トリアミノイミノホスホランを塩基触媒とし、過酸化水素を酸化剤として用いたN-スルホニルイミンの不斉酸化反応を報告した。本反応は量論量のトリクロロアセトニトリルを添加することで円滑に進行する。

The studies on the development of a highly enantioselective oxidation of N-sulfonyl imines with hydrogen peroxide-trichloroacetonitrile system utilizing P-spiro chiral triaminoiminophosphoranes as an organic base catalyst are detailed. This method is general and scalable, and exhibits unique chemo-selectivity, providing a practical stereoselective route to structurally diverse N-sulfonyl oxaziridines. The mechanistic investigations reveal that the reaction proceeds through the Payne-type oxidation pathway. The synthetic utility of the optically active N-sulfonyl oxaziridines as versatile organic oxidants and chiral building blocks is also demonstrated. (C) 2014 Elsevier Ltd. All rights reserved.

The first examples of diastereo- and enantioselective carbonyl α-(cyclopropyl)allylation are reported. Under the conditions of iridium catalyzed transfer hydrogenation using the chiral precatalyst (R)-Ir-I modified by SEGPHOS, carbonyl α-(cyclopropyl)allylation may be achieved with equal facility from alcohol or aldehyde oxidation levels. This methodology provides a conduit to hitherto inaccessible inaccessible enantiomerically enriched cyclopropane-containing architectures. Alcohol solves problems: Chiral iridium catalysts modified by (R)-SEGPHOS catalyze the transfer hydrogenative coupling of racemic α-cyclopropyl allyl acetate with diverse primary alcohols with good anti-diastereo- and exceptional enantioselectivity. These processes represent the first diastereo- and enantioselective carbonyl (α-cyclopropyl)allylations.

A red tide dinoflagellate Karenia brevis is known to produce polycyclic ethers such as the bravetoxins and brevenal. During isolation of these toxins, a new cyclic ether alkaloid named brevisamide (1) was isolated from laboratory cultured of K. brevis. The molecular formula of 1 was deduced to be C_<18>H_<29>NO_4 by HRMS and NMR spectral data. Based on 2D NMR analyses, brevisamide was found to possess a 3,4-dimethyl-2,4-heptadienal side-chain and an acetylated terminal amine. 1 is the first nitrogen-containing mono-cyclic ether from K. brevis and may provide important biogenetic clues to the origin and biosynthetic assembly of polyethers. Here we report the synthesis of 1 and its plausible biosynthetic precursors 2 and 3 supplying additional biological testing material for elucidation of biosynthetic mechanism of marine ladder-shaped polyethers.