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Chimica

セルコスポリン-フォトカタ分解[4+1]-および[4+2]-軽度の条件下でのアゾアルケンのアゾアルケンのアヌレーション

Published: July 17, 2020
doi:
10.3791/60786
, , , , , ,
1Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology,Jiangnan University, 2School of Pharmaceutical Science,Jiangnan University

Summary

セルコポリンを金属フリー光触媒として利用した窒素含有ヘテロサイクルの合成のための新しい経路が開発された。

Abstract

窒素含有ヘテロサイクルへの関心は、新薬の重要なモチーフであるため、合成界で急速に拡大しています。従来、これらは熱シクロ付加反応を介して合成されたが、今日では、軽度で効率的な条件のために光触媒が好ましい。この焦点により、窒素含有ヘテロサイクルの合成のための新しい光触媒法が非常に望まれている。ここでは、金属を含まない光触媒として機能するセルコポリンの生合成プロトコルを報告する。次に、KSCNによるアゾアルケンの環化による窒素含有ヘテロサイクル1,2,3-チアジアゾールの合成、および軽度の条件下でのアゾアルケンのシクロ二量体化を通じた1,4,5,6-テトラヒドロピリダジン[4+2]の合成に関するセルコポリン光触媒プロトコルを説明する。その結果、微生物発酵法と有機合成との間には、穏やかで費用対効果が高く、環境に優しく、持続可能な方法で新たな橋渡しが行われています。

Introduction

窒素含有ヘテロサイクルは、生物活動を有する天然物の広い範囲にとって重要な骨格であるだけでなく、農薬および薬物分子11,22の合成前駆体でもあるため、多くの注目を集めている。種々のN-ヘテロサイクルの中で、1,2,3-チアジアゾール33,44及び1,4,5,6-テトラヒドロピリダジン55,66は、合成化学において汎用性の高い中間体として利用される最も重要な分子である(図1)。それらの官能基の修飾は、常に独特の薬理活性を誘発するので、窒素含有ヘテロサイクルの合成に対する有効な戦略の開発に多大な努力が注がれ、それらは主に熱サイクロ付加反応77、8、9、108,9,10を介して合成された。今日では、持続可能な開発とグリーンケミストリーの要件を満たすために、光触媒は,、有効性15、16、17、18、19と活性化のための化学試薬15の回避を含,む,,11、12、13、14、および活性化のための化学試薬の回避を含む、非常に重要かつ利点を発揮しています11,18,1916,1712131420,,21.,強力で多目的な4ユニット中間体、 アゾアルケン(1,2-ジアジア-1,3-ジエネス)22,23,24,25,26,27,28,29,23,24,25は、ハロゲノヒドラジンおよびケトカーボン26,27,28,2930の分解のための高3効率の金属系Ru(bpy)3Cl2-光触媒反応の前駆体として採用されている。さらに、金属フリーのエオシンY光触媒システムにも使用されたが、所望の製品をわずか7%の収率で得た。金属フリー光触媒は遷移金属系光触媒に対して大きな利点を示すため、環境要因に関しては、さらに安価な価格18,19,19に関して、N-ヘテロサイクルの合成のための新しい金属フリー光触媒システムを開発することが非常に重要です。

セルコスポリン,,31、32、33、34、35、31,32,33,34,35低クレリン36、37、38、39、40、エルジノクロム36,37,38,39,4041およびフレイクロム42、43(,43図2)は、自然の中でペリイニヨン色素異色素(PQPs)に属し、内臓真菌によって産生され、 UV-vis領域での強い吸収と光化36、44、45、46、47のユニークな特性のために、光力学療法および光物理診断に適用され36,44、広く調査されている。46,4745照射時に、これらのPQPは励起状態に促され、エネルギー移動(EnT)および電子移動(ET)35、38、44、48、49、50、51、52、53、54を介して活性種53を54生成することができる。35,38,44,48,49,50,51,52,このように、我々は、これらの天然PQP,が,、55、56、57、58、59をほとんど調査されていない有機反応を駆動するために「金属55,56,フリー」光触媒として利用され得ることを想定した。575859

本明細書において、液体発酵からのセルコポリンの生合成プロトコルを報告し、それをアゾアルケンスとKSCNの[4+1]環化反応に対する金属フリー光触媒として適用し、 また[4+2]アゾアルケンのサイクロジメ化と同様に、それぞれ穏やかな条件下で高効率の1,2,3-チアジアゾールおよび1,4,5,6-テトラヒドロピリダジンを供給する(図3)。

Protocol

注: α-Halo-N-アシルヒドラゾンは公開された手順60に従って調製した。全ての溶媒及び他の化学試薬は、更なる精製を行うことなく、市販の供給源から得られた。まず、α-Halo-N-アシルNヒドラゾンの合成とセルコポリンの生合成を金属フリー光触媒として説明しました。 α次に、1,2,3-チアジアゾールおよび1,4,5,6-テトラヒドロピリダジンの合成に対す?…

Representative Results

α-Halo-N-Nアシルヒドラゾンの合成: αこれらはプロトコル 1 に従って合成されます。 セルコスポリンの合成:プロトコル2に従って合成精製した。1H NMR (400 MHz、 CDCl3): δ ppm 14.82 (s, 2H, ArH), 7.06 (s, 2H, ArH), 5.57 (s, 2H, CH2),4.20 (s, 6H, 2OCH3),3.62-3.57 (m, 2H, CH2),</sub…

Discussion

窒素含有ヘテロサイクルは、多くの新薬にとって重要なモチーフであり、伝統的にサーマルシクロ付加反応によって合成されました。大きな関心のために、これらの化合物の合成のための新しい光触媒法が非常に望まれている。セルコスポリンの優れた光化特性を利用するために、2つのカテゴリーの環化反応で、セルコスポリンを金属フリー光触媒として適用し、窒素含有ヘテロサイクルを…

Divulgazioni

The authors have nothing to disclose.

Acknowledgements

中国国家キーR&Dプログラム(2018YFA0901700)、江蘇省自然科学財団(助成金No.BK20160167)、千人の才能計画(若い専門家)、中央大学のための基礎研究資金(JUSRP51712B)、光産業技術工学の国家一流規律プログラム(LITE2018-14)、江蘇省のポスドク財団(2018K153C)。

Materials

2,4'-Dibromoacetophenone ENERGY D0500850050
2'-bromo-4-chloroacetophenone ENERGY A0500400050
2-Bromo-4'-fluoroacetophenone ENERGY A050037-5g
2-Bromoacetophenone ENERGY A0500870050
4-Bromobenzhydrazide ENERGY B0103390010
4-Chlorobenzhydrazide ENERGY D0511130050
4-Fluorobenzhydrazide ENERGY B010461-5g
5 W blue LED PHILIPS 29237328756
Benzoyl hydrazine ENERGY D0500610250
CH2Cl2 SINOPHARM 80047360
CH3CN SINOPHARM S3485101
CH3OH SINOPHARM 100141190
Cs2CO3 ENERGY E060058-25g
Ethyl acetate SINOPHARM 40065986
freeze dryer LABCONCO 7934074
HPLC Agilent 1260 Infinity II
KSCN ENERGY E0104021000
Na2SO4 SINOPHARM 51024461
organic microfiltration membrane SINOPHARM 92412511
S-7 medium Gluose 1g; Fructose 3g; Sucrose 6g; Sodium acetate 1g; Soytone 1g; Phenylalanine 5mg; Sodium benzoate 100mg; 1M KH2P04 buffer ph6.8; Biotin 1mg; Ca(NO3)2 6.5mg; Pyridoxal 1mg; Calcium pantothenate 1mg; Thiamine 1mg; MnCl2 5mg; FeCl3 2mg; Cu(NO3)2 1mg; MgSO4 3.6mg; ZnSO4 2.5mg
Schlenk tub Synthware F891910
sephadex LH-20 column GE 17009001
shaker Lab Tools BSH00847
silica gel ENERGY E011242-1kg
tBuOK ENERGY E0610551000
vacuum bump Greatwall SHB-III
vacuum evaporator
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Tags

CercosporinPhotocatalysis[4+1]-annulation[4+2]-annulationNitrogen-containing HeterocyclesAlpha-Halo-N-acyl-hydrazoneMicrobial Fermentation123-thiadiazole

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Icyishaka, P., Li, C., Lu, L., Bao, W., Li, J., Zhang, Y., Rao, Y. Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions. J. Vis. Exp. (161), e60786, doi:10.3791/60786 (2020).
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