几种4-氨基吡啶衍生物的多级质谱裂解途径
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摘要
为获得高效的海洋生物毒素河豚毒素(TTX)解毒剂,合成了一系列4-氨基吡啶类衍生物N-二异丙基磷酰化氨基酸-N-4-氨基吡啶;研究了N-二异丙基磷酰化氨基酸-N-4-氨基吡啶的多级质谱(ESI-MS/MS)裂解方式;提出了碎片离子m/z=95的裂解途径,并推测了其重排机理.结果表明,该类化合物具有相同分子量的碎片离子c/c′,是由两种母离子a或b离子裂解得到的.通过在吡啶环上引入氯原子可证实该裂解途径;而碎片离子m/z=95源于离子重排.
A series of novel 4-aminopyridine derivatives containing N-diisopropyloxyphosphoryl amino acid unit were synthesized as highly efficient antidotes of tetradotoxin,a marine organism toxin.The fragmentation pathway of as-synthesized N-diisopropyloxyphosphoryl amino acid-N-4-aminopyridines was investigated by means of positive ion electrospray ionization mass spectrometry(ESI-MS)in conjunction with tandem mass spectrometry(MS/MS).Moreover,the fragmentation pathway of fragment ion m/z=95 was proposed,and its possible rearrangement mechanism was supposed.Results indicate that all the compounds under investigation have fragment ion c/c′with the same molecular weight,and fragment ion c/c′is derived from precursor ions a and b.Such a fragmentation pathway can be verified by introducing tracer element Cl onto the pyridine ring of the title derivatives,while the fragment ion m/z = 95 is generated by way of ion rearrangement.
A series of novel 4-aminopyridine derivatives containing N-diisopropyloxyphosphoryl amino acid unit were synthesized as highly efficient antidotes of tetradotoxin,a marine organism toxin.The fragmentation pathway of as-synthesized N-diisopropyloxyphosphoryl amino acid-N-4-aminopyridines was investigated by means of positive ion electrospray ionization mass spectrometry(ESI-MS)in conjunction with tandem mass spectrometry(MS/MS).Moreover,the fragmentation pathway of fragment ion m/z=95 was proposed,and its possible rearrangement mechanism was supposed.Results indicate that all the compounds under investigation have fragment ion c/c′with the same molecular weight,and fragment ion c/c′is derived from precursor ions a and b.Such a fragmentation pathway can be verified by introducing tracer element Cl onto the pyridine ring of the title derivatives,while the fragment ion m/z = 95 is generated by way of ion rearrangement.
引文
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[12]叶勇,马利波,梁颜红,等.3-(O-甲基-O-烷基磷酰基)丙酰胺的电喷雾质谱裂解方式研究[J].质谱学报,2008,29(3):143-146.
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[14]傅玉琴,范雪娥,黄华鸣,等.α-羟基-杂(芳)环取代甲基膦酸二乙酯的合成及晶体结构[J].化学试剂,2008,30(1):1-4.
[15]ISABELLE M L,SLAYTON A E J.Studies toward the asymmetric synthesis ofγ-amino phosphonic acids via the addition of phosphites to enantiopure sulfinimines[J].J Org Chem,1997,62:7532-7533.
[16]CHEN Jing,CHEN Yi,NIU Yan Lin,et al.A carbonyl oxygen migration in electrospray ionization mass spectrometry and its application in differentiatingαandβ-alanyl peptides[J].J Mass Spectrom,2002,37:934-939.
[17]EDYTA P,PAWELK,LEONARD M P,et al.Effect of an aliphatic spacer group on the adsorption mechanism on the colloidal silver surface of L-proline phosphonodipeptides[J].J Raman Spectroscopy,2008,39(12):1726-1739.
[18]MEEHIR P,MALLARD W G,IMSUK Y.Microsynthesis and mass spectral study of chemical weapons convention related 2-alkyl-1,3,6,2-dioxathiaphosphocane-2-oxides[J].Rapid Commun Mass Spectrom,2008,22:1971-1980.
[19]ALEXANDER B,ZHANG X M,KOEN A,et al.Structure-activity relationship of diaryl phosphonate esters as potentirreversible dipeptidyl peptidase IV inhibitors[J].J Med Chem,1999,42:1041-1052.
[20]JU Zhi Yu,YE Yong,ZHONG Shang Bin,et al.A novel rearrangement in ESI-MSn of spirocyclic pentaerythritol di(phosphate monoamides)[J].Inter J Mass Spectrom,2008,273:31-34.
[2]CHANG F T C,SPRIGGS D L,BENTON B J,et al.4-Aminopyridine reverses saxitoxin(STX)-and tetrodotoxin(TTX)-induced cardiorespiratory depression in chronically instrumented guinea pigs[J].Fund Appl Toxico,1997,38(1):75-88.
[3]BERG T.The vascular response to the K+channel inhibitor 4-aminopyridine in hypertensive rats[J].Eur J Pharmacol,2003,466(2):301-310.
[4]方华,陈伟珠,洪碧红,等.N-二异丙基磷酰化氨基酸-N-4-氨基吡啶衍生物的合成及对TTX解毒生物活性的研究[J].有机化学,2012,32(1):178-182.
[5]郭洪声,何锡文,景莹,等.4-氨基吡啶分子模板聚合物选择性识别及结合性质的研究[J].高等学校化学学报,2001,22(5):739-743.
[6]宋绍丽,魏春玲,古华光,等.4-氨基吡啶敏感钾通道对神经自发放电节律转迁历程的调节作用[J].生理学报,2010,62(1):35-41.
[7]MICHAEL M,PAUL W D,WOLF-RUDIGER S.Ionic mechanism of 4-aminopyridine action on leech neuropile glial cells[J].Brain Research,1999,826(1):63-73.
[8]刘先胜,徐永健,张珍祥,等.钾通道阻滞剂对大鼠支气管平滑肌细胞增殖的影响[J].药学学报,2003,38(5):333-336.
[9]CHEN Jing,JIANG Yang,FU Hua,et al.Rearrangement with formamide extrusion in the electrospray mass spectra of aminoacylbenzylamines[J].Rapid Commun Mass Spectrom,2001,15:1489-1493.
[10]叶勇,曹立峰,牛明玉,等.三聚吡咯丝组缀合物的电喷雾电离质谱裂解规律研究[J].质谱学报,2006,27(4):203-208.
[11]董宇,仇峰,张玉峰,等.氨基甲酸酯类化合物电喷雾多级质谱分析中一种特殊的中性丢失CO2的重排反应[J].质谱学报,2005,26(1):6-9.
[12]叶勇,马利波,梁颜红,等.3-(O-甲基-O-烷基磷酰基)丙酰胺的电喷雾质谱裂解方式研究[J].质谱学报,2008,29(3):143-146.
[13]李光毅.三苯基膦和六氯乙烷肽偶联试剂的中间体研究[J].三明学院学报,2010,27(2):169-172.
[14]傅玉琴,范雪娥,黄华鸣,等.α-羟基-杂(芳)环取代甲基膦酸二乙酯的合成及晶体结构[J].化学试剂,2008,30(1):1-4.
[15]ISABELLE M L,SLAYTON A E J.Studies toward the asymmetric synthesis ofγ-amino phosphonic acids via the addition of phosphites to enantiopure sulfinimines[J].J Org Chem,1997,62:7532-7533.
[16]CHEN Jing,CHEN Yi,NIU Yan Lin,et al.A carbonyl oxygen migration in electrospray ionization mass spectrometry and its application in differentiatingαandβ-alanyl peptides[J].J Mass Spectrom,2002,37:934-939.
[17]EDYTA P,PAWELK,LEONARD M P,et al.Effect of an aliphatic spacer group on the adsorption mechanism on the colloidal silver surface of L-proline phosphonodipeptides[J].J Raman Spectroscopy,2008,39(12):1726-1739.
[18]MEEHIR P,MALLARD W G,IMSUK Y.Microsynthesis and mass spectral study of chemical weapons convention related 2-alkyl-1,3,6,2-dioxathiaphosphocane-2-oxides[J].Rapid Commun Mass Spectrom,2008,22:1971-1980.
[19]ALEXANDER B,ZHANG X M,KOEN A,et al.Structure-activity relationship of diaryl phosphonate esters as potentirreversible dipeptidyl peptidase IV inhibitors[J].J Med Chem,1999,42:1041-1052.
[20]JU Zhi Yu,YE Yong,ZHONG Shang Bin,et al.A novel rearrangement in ESI-MSn of spirocyclic pentaerythritol di(phosphate monoamides)[J].Inter J Mass Spectrom,2008,273:31-34.