氯化异黄连碱季铵盐的全合成
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摘要
目的探讨天然产物氯化异黄连碱季铵盐的全合成方法。方法以邻苯二酚为起始原料,经环合、氧化、缩合、还原和闭环5步反应合成天然产物氯化异黄连碱季铵盐。结果路线总收率为20.03%(以邻苯二酚计),其结构经~1H-NMR、~(13)C-NMR和MS谱确证。结论本合成方法原料易得、操作简单、成本较低,适合氯化异黄连碱季铵盐的批量合成,具有潜在的应用价值。
Pseudocoptisine chloride,a quaternary alkaloid with benzylisoquinoline skeleton,was isolated from the tubers of Corydalis turtschaninovii,which is one of the important medicinal plants in traditional medicine.Pseudocoptisine chloride has a variety of biological activity such as anti-inflammatory,anti-amnestic,neuraminidase inhibition and so on. Because of its natural inadequacy, this paper reports the synthetic method of a natural alkaloid quaternary pseudocoptisine chloride in overall yield of 20. 03%. The target molecule was synthesized from pyrocatechin by a five-step reaction of cyclization,o xidation,condensation, reduction,and ring-closing reaction. The structure of target compound was characterized by ~1 H-NMR,~(13) C-NMR and MS spectra. The synthesis of pseudocoptisine chloride is in few reaction steps, simple and quick operation and low cost, that is in favor of large quantities synthesis and has potential of application in the future.
Pseudocoptisine chloride,a quaternary alkaloid with benzylisoquinoline skeleton,was isolated from the tubers of Corydalis turtschaninovii,which is one of the important medicinal plants in traditional medicine.Pseudocoptisine chloride has a variety of biological activity such as anti-inflammatory,anti-amnestic,neuraminidase inhibition and so on. Because of its natural inadequacy, this paper reports the synthetic method of a natural alkaloid quaternary pseudocoptisine chloride in overall yield of 20. 03%. The target molecule was synthesized from pyrocatechin by a five-step reaction of cyclization,o xidation,condensation, reduction,and ring-closing reaction. The structure of target compound was characterized by ~1 H-NMR,~(13) C-NMR and MS spectra. The synthesis of pseudocoptisine chloride is in few reaction steps, simple and quick operation and low cost, that is in favor of large quantities synthesis and has potential of application in the future.
引文
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[8]QIN H L,WANG W J,ZHANG Z Z,et al.Derivatives of protoberberine biological alkaloids and use of same inhibiting ulcerative colitis:2789612[P].2014-10-15.
[9]MARIA G C,ENZO C,STEFANIA D M,et al.A reexamination of the methylenation reaction[J].Tetrahedron,2003,59(24):4383-4387
[10]原田胜正,白井昌志,斯波晃司,等.胡椒醛的制备方法:1400972[P].2003-03-05.
[11]王辉.洋茉莉醛的化学合成制备方法:101899033[P].2010-12-01.
[12]王国洪,黄京波.一种全合成制备洋茉莉的方法:102329297[P].2012-01-25.
[2]YUN K J,SHIN J H,CHIO J H,et al.Quaternary alkaloid,pseudocoptisine isolated from tubers of Corydalis turtschaninovii inhibits LPS-induced nitric oxide,PGE 2,and pro-inflammatory cytokines production via the dow n-regulation of NF-κB in RAW264.7 murine macrophage cells[J].Int J Immunopharmacol,2009,9(11):1323-1331.
[3]HUNG T M,NGOC T M,YOUN U J,et al.Antiamnestic activity of pseudocoptisine from Corydalis tuber[J].Biol Pharm Bull,2008,31(1):159-162.
[4]KIM J H,RYU Y B,LEE W S,et al.Neuraminidase inhibitory activities of quaternary isoquinoline alkaloids from Corydalis turtschaninovii rhizome[J].Bioorg M ed Chem,2014,22(21):6047-6052.
[5]冀娜,花尔并,高英豪.一种胡椒基乙醇及其衍生物的合成方法:102617543[P].2012-08-01.
[6]OLENA B,RONNY N.Synthesis of aromatic aldehydes by oxidative hydroxymethylation[J].Synlett,2004,35(47):1575-1576.
[7]HISASHI M,KIYOFUMI N,TOSHIO M,et al.Hepatoprotective amide constituents from the fruit Piper chaba:structural requirements,mode of action,and new amides[J].Bioorg M ed Chem,2009,17(20):7313-7323.
[8]QIN H L,WANG W J,ZHANG Z Z,et al.Derivatives of protoberberine biological alkaloids and use of same inhibiting ulcerative colitis:2789612[P].2014-10-15.
[9]MARIA G C,ENZO C,STEFANIA D M,et al.A reexamination of the methylenation reaction[J].Tetrahedron,2003,59(24):4383-4387
[10]原田胜正,白井昌志,斯波晃司,等.胡椒醛的制备方法:1400972[P].2003-03-05.
[11]王辉.洋茉莉醛的化学合成制备方法:101899033[P].2010-12-01.
[12]王国洪,黄京波.一种全合成制备洋茉莉的方法:102329297[P].2012-01-25.