Summary

세르코스포린-포토카탈루즈 [4+1]- 및 [4+2]-온화한 조건하에서 아졸케네스의 탄화

Published: July 17, 2020
doi:

Summary

금속이 없는 광촉매로서 자궁경부포린을 활용한 질소 함유 이종사이클의 합성을 위한 새로운 경로가 개발되었다.

Abstract

질소 함유 이종주기에 대한 관심은 신약에 대한 중요한 모티브이기 때문에 합성 커뮤니티에서 급속히 확대되었습니다. 전통적으로, 그들은 열 사이클로 추가 반응을 통해 합성되었다, 오늘날, 광촉매는 온화하고 효율적인 조건으로 인해 선호되는 반면. 이 초점으로, 질소 함유 이종사이클의 합성을 위한 새로운 광촉매 방법은 매우 원합니다. 여기서, 우리는 금속없는 광촉매로 작동 할 수있는 자궁 경내의 생합성을위한 프로토콜을보고합니다. 그런 다음 KSCN을 함유한 아조알켄의 탄화를 통해 질소 함유 이종사이클 1,2,3티아디아졸의 합성을 위한 자궁경수포린-포토카틸분해 프로토콜을 설명하고, 각각 1,4,5,6-테트라하이드로피리다진의 합성[4+2]을 각각 초종의 경골저경액을 통해 설명한다. 그 결과, 미생물 발효 방법과 유기 합성 사이에 는 온화하고 비용 효율적이며 환경 친화적이고 지속 가능한 방식으로 새로운 다리가 있습니다.

Introduction

질소 함유 이종사이클은 생체 활동이 있는 광범위한 천연 제품에 중요한 골격일 뿐만 아니라 농약 및 약물 분자1,,2에대한 합성 전구체이기 때문에 많은 관심을 끌고 있다. 다양한 N-이종사이클 N중, 1,2,3-티아디아졸3,,4, 1,4,5,6-테트라하이드로피리다진 5,,6은 합성 화학에서 다재다능한 중질체로 활용되는 가장 중요한 분자(도1)이다. 그들의 기능성 군의 수정은 항상 특유의 약리활동을 유도하기 때문에, 질소 함유 이질사이클의 합성을 위한 효과적인 전략을 개발하는 데 광범위한 노력이 투입되어 왔으며, 대부분 열 순환 투과 반응을 통해 합성되었다7,,8,,9,,10. 요즘, 지속 가능한 개발 및 녹색 화학의 요구 사항을 충족하기 위해, 포토카탈리시스는 큰 중요성과 장점을 발휘하고있다11,,12,,13,,14,이는 효과15를포함,16,,17,,18,,19 활성화에 대한 stoichiometric 시약의 회피20,,21., 강력하고 다재다능한 4유닛 중급자, 아졸케네스(1,2-디아자-1,3-디엔)3022,,23,,24,25,,26,,27,,,28,,29,금속계 루(bpy)3Cl 2-포토카탈리제 반응으로 사용되어 후광소 히라진과 케아칼레 의 제분에 대한 고효율의 반응.2 또한 금속이 없는 Eosin Y 포토카탈리제드 시스템에도 사용되었지만 원하는 제품을 7%의 수율로 만 제공했습니다. 금속이 없는 광촉매는 환경적 요인뿐만 아니라 저렴한가격(18,,19)에대해 전이 금속 기반 광촉매에 비해 큰 이점을 나타내기 때문에, N-이종사이클의합성을 위한 새로운 금속 없는 광촉매 시스템을 개발하는 것이 매우 중요하다.

세르코스포린31,,32,,33,,34, 35,,35저슈클레린36,,37,,38,,39,,40,엘시노크롬41 및 플리크롬,42,,43 (그림 2)본질적으로 perylenequinonoid 안료 (PQPs)에 속하며, 내시경 곰팡이에 의해 생산되고 있습니다. 이들의 광물리및 광생물학적 특성에 대해 널리 조사되어 왔으며, 자외선 부전에서의 강한 흡수와 광합성36,44,,45,,46, 47의,독특한 특성으로 인해 광역학 치료 및 광물리학적 진단에적용되었다. 조사 시, 이러한 PQPs는 흥분 된 상태로 자극된 다음 에너지 전송 (EnT) 및 전자 전달 (ET)35,38,,44,,48,,49,,,50,,51,,52,,53,,54를통해 활성 종을 생성할 수 있습니다. 따라서, 이러한 천연 PQPs는,,55,56,57,58,59에거의 조사되지 않은 유기 반응을 구동하기 위해 “금속이 없는” 광촉매로 활용될 수 있다고구상했다.,

본명, 액체 발효로부터 자궁경막포린의 생합성에 대한 프로토콜을 보고한 다음 아조알케인 및 KSCN의 [4+1] 무효화 반응에 대한 금속없는 광촉매로 적용하고, 뿐만 아니라 【4+2】아조알케인의 사이클로디머화는 1,2,3-티아디아졸과 1,4,5,6-테트라하이드로피리다진을 각각 온화한 조건하에서 고효율로 공급한다(그림3).

Protocol

참고 : α-Halo-N-아실 히드라존은 공표된절차(60)에따라 제조하였다.N 모든 용매 및 기타 화학 시약은 추가 정화 없이 상업적 인 공급원으로부터 수득하였다. 우리는 먼저 α-Halo-N-아실-히드라존의 합성과 자궁 경부의 생합성을 금속이 없는 광촉매로 기술했습니다. αN 다음으로, 우리는 1,2,3 티아디아졸과 1,4,5,6-테트라 하이드로피리다진의 합성을 위한 자?…

Representative Results

α-헤일로-N-아실히드라존합성: 프로토콜 1에 따라 합성됩니다. 자궁 경부의 합성: 의정서 2에 따라 합성 및 정제되었다. 1 H NMR (400 MHz, CDCl3):δ ppm 14.82 (s, 2H, ArH), 7.06 (s, 2H, ArH), 5.57 (들), 2H, CH2),4.20 (s, 6H, 2OCH3),3.62-3.57 (m, 2H, CH2),3.42-3.37 (m, 2H, CH2),</s…

Discussion

질소 함유 이종주기는 많은 신약에 중요한 모티프로, 전통적으로 열 사이클로추가 반응을 통해 합성되었다. 큰 관심으로 인해, 이러한 화합물의 합성을위한 새로운 포토 촉매 방법은 매우 원한다. cercosporin의 우수한 광감특성을 활용하기 위해, 우리는 질소 함유 이질주기를 합성하기 위해 무광택 반응의 두 가지 범주에서 금속이 없는 광촉매로서 자궁 경막반응을 적용했습니다.

<p class="jove_conte…

Divulgazioni

The authors have nothing to disclose.

Acknowledgements

중국 국립 핵심 R&D 프로그램(2018YFA0901700), 장쑤성 자연과학 재단(보조금 번호)에 감사드립니다. BK20160167, 천인재계획(청년전문가), 중앙대학의 기초연구기금(JUSRP51712B), 경산업기술공학국가일등급학원학원학원(LITE2018-14), 장쑤성 박사후재단(2018K153C) 지원

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

Riferimenti

  1. Majumdar, K. C., Chattopadhyay, S. K., ed, . Heterocycles in Natural Product Synthesis. , (2011).
  2. Taylor, R. D., MacCoss, M., Lawson, A. D. Rings in drugs. Journal of Medicinal Chemistry. 57 (14), 5845-5859 (2014).
  3. Bakulev, V. A., Dehaen, W. . The Chemistry of 1,2,3-Thiadiazoles. , (2004).
  4. Dong, W. L., Liu, Z. X., Liu, X. H., Li, Z. M., Zhao, W. G. Synthesis and antiviral activity of new acrylamide derivatives containing 1,2,3-thiadiazole as inhibitors of hepatitis B virus replication. European Journal of Medicinal Chemistry. 45 (5), 1919-1926 (2010).
  5. Combs, D. W., Reese, K., Phillips, A. Nonsteroidal Progesterone-Receptor Ligands. 1. 3-Aryl-1-Benzoyl-1,4,5,6-Tetrahydropyridazines. Journal of Medicinal Chemistry. 38 (25), 4878-4879 (1995).
  6. Combs, D. W., et al. Nonsteroidal Progesterone-Receptor Ligands. 2. High-Affinity Ligands with Selectivity for Bone Cell Progesterone Receptors. Journal of Medicinal Chemistry. 38 (25), 4880-4884 (1995).
  7. Xu, S. L., Chen, R. S., Qin, Z. F., Wu, G. P., He, Z. J. Divergent Amine-Catalyzed [4+2] Annulation of Morita-Baylis-Hillman Allylic Acetates with Electron-Deficient Alkenes. Organic Letters. 14 (4), 996-999 (2012).
  8. Ishikawa, T., Kimura, M., Kumoi, T., Iida, H. Coupled Flavin-Iodine Redox Organocatalysts: Aerobic Oxidative Transformation from N-Tosylhydrazones to 1,2,3-Thiadiazoles. ACS Catalysis. 7 (8), 4986-4989 (2017).
  9. Chen, J. F., Jiang, Y., Yu, J. T., Cheng, J. TBAI-Catalyzed Reaction between N-Tosylhydrazones and Sulfur: A Procedure toward 1,2,3-Thiadiazole. Journal of Organic Chemistry. 81 (1), 271-275 (2016).
  10. Liu, B. B., Bai, H. W., Liu, H., Wang, S. Y., Ji, S. J. Cascade Trisulfur Radical Anion (S3(*-)) Addition/Electron Detosylation Process for the Synthesis of 1,2,3-Thiadiazoles and Isothiazoles. Journal of Organic Chemistry. 83 (17), 10281-10288 (2018).
  11. Staveness, D., Bosque, I., Stephenson, C. R. J. Free Radical Chemistry Enabled by Visible Light-Induced Electron Transfer. Accounts of Chemical Research. 49 (10), 2295-2306 (2016).
  12. Corrigan, N., Shanmugam, S., Xu, J. T., Boyer, C. Photocatalysis in organic and polymer synthesis. Chemical Society Reviews. 45 (22), 6165-6212 (2016).
  13. Shaw, M. H., Twilton, J., MacMillan, D. W. C. Photoredox Catalysis in Organic Chemistry. Journal of Organic Chemistry. 81 (16), 6898-6926 (2016).
  14. Marzo, L., Pagire, S. K., Reiser, O., Konig, B. Visible-Light Photocatalysis: Does It Make a Difference in Organic Synthesis?. Angewandte Chemie-International Edition. 57 (32), 10034-10072 (2018).
  15. Prier, C. K., Rankic, D. A., MacMillan, D. W. C. Visible Light Photoredox Catalysis with Transition Metal Complexes: Applications in Organic Synthesis. Chemical Reviews. 113 (7), 5322-5363 (2013).
  16. Reckenthaler, M., Griesbeck, A. G. Photoredox Catalysis for Organic Syntheses. Advanced Synthesis & Catalysis. 355 (14-15), 2727-2744 (2013).
  17. Nicewicz, D. A., Nguyen, T. M. Recent Applications of Organic Dyes as Photoredox Catalysts in Organic Synthesis. ACS Catalysis. 4 (1), 355-360 (2014).
  18. Pitre, S. P., McTiernan, C. D., Scaiano, J. C. Understanding the Kinetics and Spectroscopy of Photoredox Catalysis and Transition-Metal-Free Alternatives. Accounts of Chemical Research. 49 (6), 1320-1330 (2016).
  19. Romero, N. A., Nicewicz, D. A. Organic Photoredox Catalysis. Chemical Reviews. 116 (17), 10075-10166 (2016).
  20. Albini, A., Fagnoni, M. . Photochemically-Generated Intermediates in Synthesis. , (2013).
  21. Chen, J. R., Hu, X. Q., Lu, L. Q., Xiao, W. J. Exploration of Visible-Light Photocatalysis in Heterocycle Synthesis and Functionalization: Reaction Design and Beyond. Accounts of Chemical Research. 49 (9), 1911-1923 (2016).
  22. Attanasi, O. A., et al. Cultivating the Passion to Build Heterocycles from 1,2-Diaza-1,3-dienes: the Force of Imagination. European Journal of Organic Chemistry. 19, 3109-3127 (2009).
  23. Attanasi, O. A., Filippone, P. Working twenty years on conjugated azo-alkenes (and environs) to find new entries in organic synthesis. Synlett. 10, 1128-1140 (1997).
  24. Deng, Y., Pei, C., Arman, H., Dong, K., Xu, X., Doyle, M. P. Syntheses of Tetrahydropyridazine and Tetrahydro-1,2-diazepine Scaffolds through Cycloaddition Reactions of Azoalkenes with Enol Diazoacetates. Organic Letters. 18 (22), 5884-5887 (2016).
  25. Guo, C., Sahoo, B., Daniliuc, C. G., Glorius, F. N-heterocyclic carbene catalyzed switchable reactions of enals with azoalkenes: formal [4+3] and [4+1] annulations for the synthesis of 1,2-diazepines and pyrazoles. Journal of American Chemistry Society. 136 (50), 17402-17405 (2014).
  26. Attanasi, O. A., et al. Interceptive [4+1] annulation of in situ generated 1,2-diaza-1,3-dienes with diazo esters: direct access to substituted mono-, bi-, and tricyclic 4,5-dihydropyrazoles. Journal of Organic Chemistry. 79 (17), 8331-8338 (2014).
  27. Li, J., Huang, R., Xing, Y. K., Qiu, G., Tao, H. Y., Wang, C. J. Catalytic Asymmetric Cascade Vinylogous Mukaiyama 1,6-Michael/Michael Addition of 2-Silyloxyfurans with Azoalkenes: Direct Approach to Fused Butyrolactones. Journal of the American Chemical Society. 137 (32), 10124-10127 (2015).
  28. Huang, R., Chang, X., Li, J., Wang, C. J. Cu(I)-Catalyzed Asymmetric Multicomponent Cascade Inverse Electron-Demand Aza-Diels-Alder/Nucleophilic Addition/Ring-Opening Reaction Involving 2-Methoxyfurans as Efficient Dienophiles. Journal of the American Chemical Society. 138 (12), 3998-4001 (2016).
  29. Tong, M. C., et al. Catalytic asymmetric synthesis of [2,3]-fused indoline heterocycles through inverse-electron-demand aza-Diels-Alder reaction of indoles with azoalkenes. Angew Chemistry International Edition English. 53 (18), 4680-4684 (2014).
  30. Yu, J. M., Lu, G. P., Cai, C. Photocatalytic radical cyclization of alpha-halo hydrazones with beta-ketocarbonyls: facile access to substituted dihydropyrazoles. Chemistry Communication (Camb.). 53 (38), 5342-5345 (2017).
  31. Kuyama, S., Tamura, T. Cercosporin. A pigment of Cercosporina kikuchii Matsumoto et Tomoyasu. I. Cultivation of fungus, isolation and purification of pigment. Journal of the American Chemical Society. 79 (21), 5725-5726 (1957).
  32. Kuyama, S., Tamura, T. Cercosporin. A pigment of Cercosporina kikuchii Matsumoto et Tomoyasu. II. Physical and chemical properties of cercosporin and its derivatives. Journal of the American Chemical Society. 79 (21), 5726-5729 (1957).
  33. Daub, M. E. Resistance of fungi to the photosensitizing toxin, cercosporin. Phytopathology. 77 (11), 1515-1520 (1987).
  34. Jalal, M. A. F., Hossain, M. B., Robeson, D. J., Vanderhelm, D. Cercospora-Beticola Phytotoxins – Cebetins That Are Photoactive, Mg2+-Binding, Chlorinated Anthraquinone Xanthone Conjugates. Journal of the American Chemical Society. 114 (15), 5967-5971 (1992).
  35. Daub, M. E., Ehrenshaft, M. The photoactivated Cercospora toxin cercosporin: Contributions to plant disease and fundamental biology. Annual Review of Phytopathology. 38 (1), 461-490 (2000).
  36. Diwu, Z. J., Lown, J. W. Photosensitization with Anticancer Agents. 14. Perylenequinonoid Pigments as New Potential Photodynamic Therapeutic Agents – Formation of Tautomeric Semiquinone Radicals. Journal of Photochemistry and Photobiology A-Chemistry. 69 (2), 191-199 (1992).
  37. Hu, Y. Z., An, J. Y., Jiang, L. J., Chen, D. W. Spectroscopic Study on the Photoreduction of Hypocrellin-a – Generation of Semiquinone Radical-Anion and Hydroquinone. Journal of Photochemistry and Photobiology A-Chemistry. 89 (1), 45-51 (1995).
  38. Hu, Y. Z., Jiang, L. J., Chiang, L. C. Characteristics of the reaction between semiquinone radical anion of hypocrellin A and oxygen in aprotic media. Journal of Photochemistry and Photobiology A-Chemistry. 94 (1), 37-41 (1996).
  39. Zhang, M. H., et al. Study of electron transfer interaction between hypocrellin and N,N-diethylaniline by UV-visible, fluorescence, electron spin resonance spectra and time-resolved transient absorption spectra. Journal of Photochemistry and Photobiology A-Chemistry. 96 (1-3), 57-63 (1996).
  40. He, Y. Y., An, J. Y., Jiang, L. J. pH Effect on the spectroscopic behavior and photoinduced generation of semiquinone anion radical of hypocrellin B. Dyes and Pigments. 41 (1-2), 79-87 (1999).
  41. Li, C., et al. Photophysical and photosensitive properties of Elsinochrome A. Chinese Science Bulletin. 51 (9), 1050-1054 (2006).
  42. So, K. K., et al. Improved production of phleichrome from the phytopathogenic fungus Cladosporium phlei using synthetic inducers and photodynamic ROS production by phleichrome. Journal of Bioscience and Bioengineering. 119 (3), 289-296 (2015).
  43. Hudson, J. B., Imperial, V., Haugland, R. P., Diwu, Z. Antiviral activities of photoactive perylenequinones. Photochemistry and Photobiology. 65 (2), 352-354 (1997).
  44. Diwu, Z. J., Lown, J. W. Photosensitization by Anticancer Agents. 12. Perylene Quinonoid Pigments, a Novel Type of Singlet Oxygen Sensitizer. Journal of Photochemistry and Photobiology A-Chemistry. 64 (3), 273-287 (1992).
  45. Diwu, Z. J., Zimmermann, J., Meyer, T., Lown, J. W. Design, Synthesis and Investigation of Mechanisms of Action of Novel Protein-Kinase-C Inhibitors – Perylenequinonoid Pigments. Biochemical Pharmacology. 47 (2), 373-385 (1994).
  46. Guedes, R. C., Eriksson, L. A. Photophysics, photochemistry, and reactivity: Molecular aspects of perylenequinone reactions. Photochemical & Photobiological Sciences. 6 (10), 1089-1096 (2007).
  47. Mulrooney, C. A., O’Brien, E. M., Morgan, B. J., Kozlowski, M. C. Perylenequinones: Isolation, Synthesis, and Biological Activity. European Journal of Organic Chemistry. (21), 3887-3904 (2012).
  48. Daub, M. E., Hangarter, R. P. Light-induced production of singlet oxygen and superoxide by the fungal toxin, cercosporin. Plant Physiololgy. 73 (3), 855-857 (1983).
  49. Daub, M. E., Leisman, G. B., Clark, R. A., Bowden, E. F. Reductive Detoxification as a Mechanism of Fungal Resistance to Singlet Oxygen-Generating Photosensitizers. Proceedings of the National Academy of Sciences of the United States of America. 89 (20), 9588-9592 (1992).
  50. Leisman, G. B., Daub, M. E. Singlet Oxygen Yields, Optical-Properties, and Phototoxicity of Reduced Derivatives of the Photosensitizer Cercosporin. Photochemistry Photobiology. 55 (3), 373-379 (1992).
  51. Bilski, P., Li, M. Y., Ehrenshaft, M., Daub, M. E., Chignell, C. F. Vitamin B6 (pyridoxine) and its derivatives are efficient singlet oxygen quenchers and potential fungal antioxidants. Photochemistry Photobiology. 71 (2), 129-134 (2000).
  52. Xing, M. Z., Zhang, X. Z., Sun, Z. L., Zhang, H. Y. Perylenequinones act as broad-spectrum fungicides by generating reactive oxygen species both in the dark and in the light. Journal of Agricultural and Food Chemistry. 51 (26), 7722-7724 (2003).
  53. Weng, M., Zhang, M. H., Shen, T. Electron transfer interaction between hypocrellin A and biological substrates and quantitative analysis of superoxide anion radicals. Journal of the Chemical Society-Perkin Transactions. 2 (11), 2393-2397 (1997).
  54. Daub, M. E., Li, M., Bilski, P., Chignell, C. F. Dihydrocercosporin singlet oxygen production and subcellular localization: A possible defense against cercosporin phototoxicity in Cercospora. Photochemistry and Photobiology. 71 (2), 135-140 (2000).
  55. Zhang, S. W., et al. Perylenequinonoid-catalyzed photoredox activation for the direct arylation of (het)arenes with sunlight. Organic & Biomolecular Chemistry. 17 (17), 4364-4369 (2019).
  56. Zhang, Y., et al. Perylenequinonoid-Catalyzed [4+1]-and [4+2]-Annulations of Azoalkenes: Photocatalytic Access to 1, 2, 3-Thiadiazole/1, 4, 5, 6-Tetrahydropyridazine Derivatives. Journal of Organic Chemistry. 84 (12), 7711-7721 (2019).
  57. Li, J., et al. Cercosporin-Bioinspired Selective Photooxidation Reactions under Mild Conditions. Green Chemistry. 21 (22), 6073-6081 (2019).
  58. Tang, Z., et al. Cercosporin-bioinspired photoreductive activation of aryl halides under mild conditions. Journal of Catalysis. 380, 1-8 (2019).
  59. Li, J., Bao, W., Zhang, Y., Rao, Y. Cercosporin-photocatalyzed sp3 (C-H) Activation for the Synthesis of Pyrrolo[3,4-c]quinolones. Organic & Biomolecular Chemistry. 17 (40), 8958-8962 (2019).
  60. Wang, F., Chen, C., Deng, G., Xi, C. J. Concise Approach to Benzisothiazol-3(2H)-one via Copper-Catalyzed Tandem Reaction of o-Bromobenzamide and Potassium Thiocyanate in Water. Journal of Organic Chemistry. 77 (8), 4148-4151 (2012).

Play Video

Citazione di questo articolo
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).

View Video