小黄皮枝叶中化学成分研究
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摘要
综合运用硅胶柱色谱、ODS柱色谱、Sephadex LH-20凝胶柱色谱以及制备型高效液相色谱等现代色谱分离技术对芸香科黄皮属植物小黄皮Clausena emarginata枝叶中的化学成分进行系统研究。根据化合物的理化性质和波谱数据,并通过与文献对照,鉴定了从小黄皮枝叶的90%乙醇提取物中分离得到的16个化合物,分别鉴定为:siamenol (1),murrastanine A(2),3-formyl-1,6-dimethoxycarbazole (3),3-methoxymethylcarbazole (4),3-methylcarbazole (5),murrayafoline A (6),3-formylcarbazole (7),3-formyl-1-hydroxycarbazole (8),3-formyl-6-methoxycarbazole (9),murrayanine (10),murrayacine (11),girinimbine (12),nordentatin (13),chalepin (14),8-hydroxy-6-methoxy-3-pentylisocoumarin (15)和ethyl orsellinate (16),其中化合物1～12为咔唑生物碱类化合物,化合物13和14为香豆素类化合物,化合物15和16为酚酸类化合物。化合物1～4,14～16为首次从小黄皮中分离得到,其中化合物1,2,15和16为首次从黄皮属植物中分离得到。对分离得到的所有化合物的细胞毒活性进行了评价,评价结果表明化合物12和14对5株人肿瘤细胞株(HL-60,A549,SMMC-7721,MCF-7和SW480)均显示出了较为显著的生长抑制活性,其细胞毒活性与抗肿瘤阳性对照药阿霉素的活性相当。
The chemical constituents from the stems and leaves of Clausena emarginata were separated and purified by column chromatographies on silica gel,ODS,Sephadex LH-20,and PR-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis,as well as comparisons with the data reported in the literature. Sixteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. emarginata,which were identified as siamenol( 1),murrastanine A( 2),3-formyl-1,6-dimethoxycarbazole( 3),3-methoxymethylcarbazole( 4),3-methylcarbazole( 5),murrayafoline A( 6),3-formylcarbazole( 7),3-formyl-1-hydroxycarbazole( 8),3-formyl-6-methoxycarbazole( 9),murrayanine( 10),murrayacine( 11),girinimbine( 12),nordentatin( 13),chalepin( 14),8-hydroxy-6-methoxy-3-pentylisocoumarin( 15) and ethyl orsellinate( 16). Compounds 1-4,14-16 were isolated from C. emarginata for the first time. Among them,compounds 1,2,15 and 16 were isolated from the genus Clausena for the first time. All isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines: HL-60,SMMC-7721,A-549,MCF-7 and SW480 in vitro. Compounds 12 and 14 showed significant inhibitory effects against various human cancer cell lines with IC_(50) values comparable to those of doxorubicin.
The chemical constituents from the stems and leaves of Clausena emarginata were separated and purified by column chromatographies on silica gel,ODS,Sephadex LH-20,and PR-HPLC. The structures of the isolated compounds were identified on the basis of physicochemical properties and spectroscopic analysis,as well as comparisons with the data reported in the literature. Sixteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. emarginata,which were identified as siamenol( 1),murrastanine A( 2),3-formyl-1,6-dimethoxycarbazole( 3),3-methoxymethylcarbazole( 4),3-methylcarbazole( 5),murrayafoline A( 6),3-formylcarbazole( 7),3-formyl-1-hydroxycarbazole( 8),3-formyl-6-methoxycarbazole( 9),murrayanine( 10),murrayacine( 11),girinimbine( 12),nordentatin( 13),chalepin( 14),8-hydroxy-6-methoxy-3-pentylisocoumarin( 15) and ethyl orsellinate( 16). Compounds 1-4,14-16 were isolated from C. emarginata for the first time. Among them,compounds 1,2,15 and 16 were isolated from the genus Clausena for the first time. All isolated compounds were evaluated for their cytotoxic activities against five human cancer cell lines: HL-60,SMMC-7721,A-549,MCF-7 and SW480 in vitro. Compounds 12 and 14 showed significant inhibitory effects against various human cancer cell lines with IC_(50) values comparable to those of doxorubicin.
引文
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[16] Cui C B,Yan S Y,Cai B,et al. Carbazole alkaloids as new cell cycle inhibitor and apoptosis inducers from Clausena dunniana levl[J]. J Asian Nat Prod Res,2002,4(4):233.
[17] Oliveria F M,Sant'Ana A E G,Conserva L M,et al. Alkaloids and coumarins from Esenbeckia species[J]. Phytochemistry,1996,41(2):647.
[18] Kihampa C,Nkunya M H H,Joseph C C,et al. Mosquitocidal and antimicrobial nor-halimane diterpenes from Tessmannia densiflora[J]. Phytochemistry,2009,70:1233.
[19]邱澄,丁怡.石耳化学成分的研究[J].中国中药杂志,2001,26(9):608.
[20] Fu Y H,Di Y T,He H P,et al. Angustifonines A and B,cytotoxic bisindole alkaloids from Bousigonia angustifolia[J]. J Nat Prod,2012,77(1):57.
[21]高启龙,朱亚楠,石变,等.青龙衣含药血清抑制胃癌SGC-7901细胞生长和诱导凋亡[J].中国实验方剂学杂志,2017,23(13):111.
[2] Xia H M,Li C J,Yang J Z,et al. A,D-seco-limonoids from the stems of Clausena emarginata[J]. J Nat Prod,2014,77(4):784.
[3] Xia H M,Li C J,Yang J Z,et al. Anti-inflammatory amide alkaloids from the stems of Clausena emarginata[J]. J Asian Nat Prod Res,2014,16(10):971.
[4] Xia H M,Ou Yang G Q,Li C J,et al. Clauemarazoles A-G,seven carbazole alkaloids from the stems of Clausena emarginata[J]. Fitoterapia,2015,103:83.
[5] Xia H M,Li C J,Yang J Z,et al. Hepatoprotective pyranocoumarins from the stems of Clausena emarginata[J]. Phytochemistry,2016,130:238.
[6] Wei R R,Ma Q G,Li,T,et al. Carbazole alkaloids with antiangiogenic activities from Clausena sanki[J]. Bioorg Chem,2018,77:387.
[7] Meragelman K M,Mc Kee T C,Boyd M R. Siamenol,a new carbazole alkaloid from Murraya siamensis[J]. J Nat Prod,2000,63(3):427.
[8] Tan S P,Ali A M,Nafiah M A,et al. Isolation and cytotoxic investigation of new carbazole alkaloids from Murraya koenigii(Linn.)Spreng[J]. Tetrahedron,2015,71(23):3946.
[9] Li W S,Mc Chesney J D,El-Feraly F S. Carbazole alkaloids from Clausena lansium[J]. Phytochemistry,1991,30(1):343.
[10] Yan S Y,Cui C B,Cai B,et al. New carbazole alkaloid from Clausena dunniana Levl[J]. Chin J Med Chem,2001,11(6):345.
[11] Ahmad K,Tan S P,Sukari M A,et al. Cytotoxic and antitumour promoting activities of carbazole alkaloids from Malayan Murraya koenigii(L.)Spreng[J]. Am J Plant Sci,2014,5(19):2869.
[12] Ackermann L,Althammer A,Mayer P. Palladium-catalyzed direct arylation-based domino synthesis of annulated N-heterocycles using alkenyl or(hetero)aryl 1,2-dihalides[J]. Synthesis,2009,2009(20):3493.
[13]柳航,沈纪中,张海霞.假黄皮茎枝化学成分研究[J].中药材,2014,37(11):2012.
[14]彭文文,刘欣媛,曾广智,等.小叶臭黄皮咔唑生物碱化学成分及其抗肿瘤活性研究[J].中草药,2016,47(6):886.
[15] Dai J X,Ma D K,Fu C L,et al. Gram scale total synthesis of 2-hydroxy-3-methylcarbazole,pyrano[3,2-a] carbazole and prenylcarbazole alkaloids[J]. Eur J Org Chem,2015,2015(25):5655.
[16] Cui C B,Yan S Y,Cai B,et al. Carbazole alkaloids as new cell cycle inhibitor and apoptosis inducers from Clausena dunniana levl[J]. J Asian Nat Prod Res,2002,4(4):233.
[17] Oliveria F M,Sant'Ana A E G,Conserva L M,et al. Alkaloids and coumarins from Esenbeckia species[J]. Phytochemistry,1996,41(2):647.
[18] Kihampa C,Nkunya M H H,Joseph C C,et al. Mosquitocidal and antimicrobial nor-halimane diterpenes from Tessmannia densiflora[J]. Phytochemistry,2009,70:1233.
[19]邱澄,丁怡.石耳化学成分的研究[J].中国中药杂志,2001,26(9):608.
[20] Fu Y H,Di Y T,He H P,et al. Angustifonines A and B,cytotoxic bisindole alkaloids from Bousigonia angustifolia[J]. J Nat Prod,2012,77(1):57.
[21]高启龙,朱亚楠,石变,等.青龙衣含药血清抑制胃癌SGC-7901细胞生长和诱导凋亡[J].中国实验方剂学杂志,2017,23(13):111.