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Abstract
Introduction
Protocol
Results
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Chemistry

神经素-光催化 [4]1]- 和 [4]2]- 在轻度条件下对阿佐尔克内斯的无效

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

开发了利用脑电图素作为无金属光催化剂合成含氮异循环的新途径。

Abstract

由于含氮杂物是新药的重要图案，人们对含氮杂物的兴趣在合成社区中迅速扩大。传统上，它们是通过热循环反应合成的，而今天，由于温和高效的条件，光催化是首选。以这种焦点，一种新的光催化方法合成含氮异循环是高度需要的。在这里，我们报告一个协议，即脑孢子素的生物合成，它可以作为无金属光催化器。然后，我们演示了通过用 KSCN 废除阿佐克酮合成含氮异循环 1，2，3-硫二氮的脑膜-光催化协议，以及通过温和条件下的亚生酮循环化合成 1，4，5，6-四氢化物 [4]2] 的合成。因此，微生物发酵法与有机合成之间以温和、经济、环保和可持续的方式架起一座桥梁。

Introduction

含氮杂物不仅成为生物活性植物中各种天然产品的重要骨架，而且是农用化学品和药物分子1、2的合成前体，因此备受关注。在各种N-异环中，1，2，3-硫化物,3，4和1，4，5，6-四3氢酶5，66是最重要的分子，在合成化学中用作5多功能中间体（图1）。由于其功能群的改性总是诱发独特的药理活性，因此，他们广泛致力于制定有效的氮气异循环合成策略，它们大多通过热细胞载反应,,7、8、9、108合成。79目前，为满足可持续发展和绿色化学的要求，光催化已发挥十一、十二、十,三、十四等十分重要和优势，包括,,,,有效15、16、17、18、19和避免活化15,16181720、21的化学试剂。19 21功能强大、多功能的四单元中间体， azoalkenes （1，2-diaza-1，3-dienes）22，,23，,24，,25，,26，,27，,28，,29，已被使用作为前体在金属为基础的Ru（bpy）3Cl2-光催化反应与高效率的卤素氢化物和酮碳素30的环烷。此外，它也用于无金属Eosin Y光催化系统，但只提供7%的产能所需的产品。由于无金属光催化剂比过渡金属基光催化剂具有很大的优势，在环境因素以及更便宜的价格18，19，,19这是非常重要的，开发新的无金属光催化系统合成N-异轮。

Cercosporin31，,,32，,33，,34，,35，低,氯林36，,37，,38，,39，,40，elsinochrome41和 phleichrome42，,43 （图 2）属于苯基诺酮类色素 （PQPs） 在自然界中， 由于其在紫外线区域的强烈吸收和光敏化36、44、45、46、47的独特特性，已广泛研究其光物理和光生物学特性，46并应用于光动力治疗和光物理诊断。,44辐照后，这些PQP可以提示兴奋状态，然后产生活性物种通过能量转移（EnT）和电子转移（ET）35，38，44，48，49，50，51，52，53，54。35,38,44,48,49,50,51,52,53,54因此，我们设想，这些天然PQPs可以用作”无金属”光催化剂，以推动有机反应，这很少被调查55，56，57，58，59。55,56,57,58,59

在这里，我们报告液体发酵中脑孢素的生物合成协议，然后将其作为无金属光催化剂应用于阿佐克内和 KSCN 的 [4]]1] 无效反应， 以及[4][2]环化阿佐克尼，分别提供1，2，3-硫化物和1，4，5，6-四氢化物，在温和条件下效率高（图3）。

Protocol

注：\-Halo-N-acyl-hydrazone）是按照公布的程序60编制的。 αN所有溶剂和其他化学试剂均从商业来源获得，无需进一步纯化。我们首先将α-Halo-N-acyl-hydrazone的合成和脑孔磷酸的生物合成描述为无金属光催化剂。 αN接下来，我们说明了用于合成1，2，3-硫化物和1，4，5，6-四氢化物的脑膜-光催化反应的协议。 注意：所有操作应佩戴手套、?…

Representative Results

合成+ -哈洛 -N- acyl – 海德拉酮：它们根据议定书1合成。 脑孢素合成：它根据议定书2进行合成和纯化。1H NMR （400 MHz， CDCl3）： μ ppm 14.82 （s， 2H， ArH）， 7.06 （s， 2H， ArH）， 5.57 （s， 2H， CH2）， 4.20 （s， 6H， 2OCH 3 ）， 3.62-3.57 （m， 2H， CH2）， 3.42-3…

Discussion

含氮的杂循环是许多新药的重要图案，传统上是通过热囊肿反应合成的。由于兴趣很大，一种新的光催化方法合成这些化合物是高度期望的。为了利用塞高素优异的光敏特性，我们应用脑电图素作为无金属光催化剂，在两类去功能化反应中合成含氮异循环。

首先，我们报告了在标准条件下用 KSCN 废除佐烷的酶协议 [4]1] 标准条件下： α-halo-N– acyl – hydrazone 1 ?…

Disclosures

The authors have nothing to disclose.

Acknowledgements

我们感谢中国国家重点研发项目（2018YFA0901700），江苏省自然科学基金（赠款第1号）。BK20160167）、”千人计划”（青年专业人才）、中央高校基础研究基金（51712B）、国家轻工技术与工程一级学科计划（LITE2018-14）和江苏省博士后资助基金会（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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