2018年度研究成果

7) Total synthesis of (-)-agelastatin A: an SH2’ radical azidation strategy

Izuru Tsuchimochi, Yuta Kitamura, Hiroshi Aoyama, Shuji Akai, Keiyo Nakai, Takehiko Yoshimitsu*, Chem. Commun., 54, 9893-9896. DOI: 10.1039/c8cc05697h Cited as a cover picture

Abstract: A reagent generated from TMSN3/KMnO4/BnEt3NCl was found to promote an SH2’ radical azidation of a bromo silyl enol ether to furnish an azido silyl enol ether via olefin transposition. With the present azidation protocol, a new synthetic approach to agelastatin A, a potent antitumor marine alkaloid, has been established.

 

6) Flow Synthesis of (3R)- and (3S)-(E)-1-Iodohexa-1,5-dien-3-ol: Chiral Building Blocks for Natural Product Synthesis

Sota Katayama, Tomoyuki Koge, Satoko Katsuragi, Shuji Akai, and Tohru Oishi* Chem. Lett. 47, in press (2018). DOI:10.1246/cl.180475

Abstract: A concise procedure to prepare optically active (3R)- and (3S)-(E)-1-iodohexa-1,5-dien-3-ol was developed. The racemic alcohol was prepared under flow and batch conditions via successive half reduction of the ester followed by Grignard reaction. Lipase catalyzed kinetic resolution under flow conditions afforded (3S)- alcohol and corresponding (3R)-acetate. The acetyl group was removed under flow conditions by using ion exchange resin.

 

5)  Lipase-Catalyzed Dynamic Kinetic Resolution of C1- and C2- Symmetric Racemic Axially Chiral 2,2'-Dihydroxy-1,1'-biaryls

Gamal A. I. Moustafa, Yasuhiro Oki, Shuji Akai, Angew. Chem. Int. Ed., 57,10278-10282 (2018), DOI:10.1002/anie.201804161

Abstract: We have discovered that the racemization of configurationally stable, axially chiral 2,2’-dihydroxy-1,1’-biaryls proceeds with a catalytic amount of a cyclopentadienylruthenium(II) complex at 35–50 °C. Combining this racemization procedure with lipase-catalyzed kinetic resolution led to the first lipase/metal-combo-catalyzed dynamic kinetic resolution of racemic axially chiral biaryls. The method was applied to the synthesis of various enantio-enriched C1- and C2-symmetric biaryl diols in yields of up to 98% and enantiomeric excesses of up to 98%, which paves the way for new developments in the field of asymmetric synthesis.

 

4)  Lipase-catalyzed asymmetric synthesis of naphtho[2,3-c]furan-1(3H)-one derivatives by a one-pot dynamic kinetic resolution/intramolecular Diels–Alder reaction: Total synthesis of (–)-himbacine

Koji Sugiyama, Shinji Kawanishi, Yasuhiro Oki, Marin Kamiya, Ryosuke Hanada, Masahiro Egi, Shuji Akai, Bioorg. Med. Chem., 26, 1378-1386 (2018), DOI:10.1016/j.bmc.2017.08.019

Abstract: One-pot sequential reactions using the acyl moieties installed by enzymatic dynamic kinetic resolution of alcohols have been little investigated. In this work, the acryloyl moiety installed via the lipase/oxovanadium combo-catalyzed dynamic kinetic resolution of a racemic dienol [4-(cyclohex-1-en-1-yl)but-3-en-2-ol or 1-(cyclohex-1-en-1-yl)but-2-en-1-ol] with a (Z)-3-(phenylsulfonyl)acrylate underwent an intramolecular Diels–Alder reaction in a one-pot procedure to produce an optically active naphtho[2,3-c]furan-1(3H)-one derivative (98% ee). This method was successfully applied to the asymmetric total synthesis of (–)-himbacine.

 

3)  オキソバナジウム/加水分解酵素混合触媒による第二級アルコールの動的光学分割:メソポーラスシリカの細孔の活用
Dynamic Kinetic Resolution of Secondary Alcohols by Oxovanadium/Hydrolase Combo-Catalysis: Effective Use of Mesoporous Silicas

赤井周司, ゼオライト, 35, 23-29 (2018); Shuji Akai, Zeolite, 35, 23-29 (2018)

Abstract: The dynamic kinetic resolution (DKR) has gained increasing attention because it is a simple method to obtain optically pure compounds from racemic substrates in quantitative yields. DKR is typically performed by a combination of kinetic resolution of racemates and in situ, continuous, and rapid interconversion between two enantiomers of the substrates, namely, racemization. We recently reported a new DKR method based on the combination of lipase-catalyzed kinetic resolution of racemic secondary alcohols and the V-MPS-catalyzed in situ racemization. In V-MPS, oxovanadium moieties were covalently bound to the inner surface of mesoporous silica (MPS) with a pore size of 2–4 nm. In this article, we introduce the background of why we used MPS, reaction characteristics of V-MPS, advantages of our DKR method, and its synthetic applications.

 

2)  3-(Triflyloxy)benzynes Enable the Regiocontrolled Cycloaddition of Cyclic Ureas to Synthesize 1,4-Benzodiazepine Derivatives

Hideki Kaneko, Takashi Ikawa, Yuta Yamamoto, Sundaram Arulmozhiraja, Hiroaki Tokiwa, Shuji Akai, Synlett, 29, 943-948 (2018), DOI:10.1055/s-0036-1591924

Abstract: A versatile synthesis of 1,4-benzodiazepine derivatives through the reaction of various 3-(trifluoromethanesulfonyloxy)benzynes with N-(p-toluenesulfonyl)imidazolidin-2-ones is reported. This reaction system provides a 1,4-benzodiazepine bearing a trifluoromethanesulfonyloxy group as a single regioisomer among the four possible regioisomers.

 

1)  Synthesis of Optically Active 2,3-Disubstituted Indoline Derivatives through Cycloaddition Reactions between Benzynes and α,β-Unsaturated γ-Aminobutyronitriles

Takashi Ikawa, Yuta Sumii, Shigeaki Masuda, Ding Wang, Yuto Emi, Akira Takagi, Shuji Akai, Synlett, 29, 530–536 (2018), DOI:10.1055/s-0036-1591722

Abstract: We report a method for synthesizing optically active 2,3-disubstituted indolines by the cycloaddition reaction of benzynes with various 4-[(4-toluenesulfonyl)amino]-(E)-but-2-enenitriles, which are readily prepared from the corresponding ʟ-amino acid derivatives.