蚓参生物活性成分研究
摘要
本文对采自我国海南三亚的海洋动物蚓参(Holothuria arenicola Semper),又名沙海参,在我国南海海域有广泛的分布,可供食用。其生物活性成分的研究国内外均未具有过报道。本研究以稻瘟霉模型作为活性监测手段,应用正相硅胶、反相硅胶、葡聚糖凝胶以及高效液相色谱法等多种色谱分离技术,对蚓参所含的抗肿瘤和抗真菌活性成分进行了系统的分离纯化和生物活性研究。共分离得到单体化合物18个,应用现代波谱技术和化学手段鉴定了其中12个化合物的结构,均为首次从该海参中分离获得,其中新化合物6个。
在化学结构测定中,特别采用~1HNMR、~(13)CNMR和二维核磁共振技术(DQCOSY、TOCSY、HMQC、HMBC和NOESY等)和电喷雾离子质谱以及化学方法(水解,化学鉴别),确定了这些化合物的化学结构。其中8个海参皂苷的化学结构为:3-O-[3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α,17α-三醇(HA-1, holothurin A),3-O-[3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-海参烷-9(11)-烯-22-羟基-3β,12α,17α-三醇(HA-2, holothurin A1),3-O-[3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α-二醇(HA-3, fuscoineroside C),3-O-[3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-海参烷-9(11)-烯-3β,12α,17α-三醇(HA-4, echinoside A),3-O-[3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸基-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α,17α-三醇(HA-5, arenicolaside A),3-O-[3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸基-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α-二醇(HA-6, arenicolaside B),3-O-[β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α,17α-三醇(HA-7, holothurin B),3-O-[β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-海参烷-9(11)-烯-3β,12α,17α-三醇(HA-8, echinoside B)。4个甾体化合物:3β-硫酸酯基-24-亚甲基-5α-7(8)-胆甾烯(HA-9,arenicolaside C),3β-硫酸酯基-24-亚甲基-5α-胆甾(HA-10,arenicolaside D),3β-硫酸酯基-24-乙基-5α-7,22E-胆甾二烯(HA-11,arenicolaside E),3β-硫酸酯基-24-乙基-5α-7(8)-胆甾烯(HA-12,arenicolaside F)。其中6个化合物(H A-5、HA-6和HA-9～HA-12)为新化合物。
初步的药理活性筛选表明,海参皂苷HA-1～HA-8,对稻瘟霉显示显著的生物活性,其中HA-1、2和4～6的MMDC值<8μg/ml;对BEL-7402人肝癌细胞、HL-60人白血病细胞、A-549人肺癌细胞和P388小鼠白血病细胞具有较强的细胞毒活性,其中HA-3对BEL-7402人肝癌细胞的抑制率为89.4%(10-6 mol/l),HA-1对A-549人肺癌细胞的抑制率为73.4%(10-8 mol/l);HA-1～HA-8对白色念珠菌、新生隐球菌、克柔式念珠菌、光滑念珠菌和近平滑念珠菌均具有不同强度的抑制生长作用,其中化合物HA-8对白色念珠菌和新生隐球菌的MIC80值达到2.1μg/ml和1.1μg/ml。
本课题首次对蚓参体内的化学成分及药理活性进行了系统的研究,研究结果为进一步研制开发新的抗肿瘤抗真菌药物提供了科学依据和有价值的先导化合物,也为海洋天然产物的研究积累了新的研究资料,对开发利用我国丰富的海参生物资源具有较重要的意义。
Holothuria arenicola Semper distributed abundantly in South China Sea. No chemical works have been performed on this sea cucumber up to date. Guided by Pyricularia oryzae bioassay model, the anti-cancer and anti-fungal constituents of Holothuria arenicola Semper have been investigated by various chromatography methods including LPLC, MPLC, HPLC on silica gel, ODS RP C18 and Zorbax SB C18 respectively. Eighteen compounds were isolated and structures of twelve compounds were elucidated by chemical and spectral analysis (IR, EI-MS, ESI-MS, HRESI-MS, ~1HNMR, ~(13)CNMR, ~1H-1H COSY, DQCOSY, TOCSY, HMQC, HMBC, NOESY, etc.).
From the ethanolic extracts of Holothuria arenicola Semper, twelve compounds were isolated and identified, including eight triterpene glycosides: 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3β,12α,17α-triol (HA-1, holothurin A), 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl- (1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-holosta-22-hydroxyholost-9(11)-ene-3β,12α,17α-triol (HA-2, holothurin A1), 3-O-[3-O-methyl-β-D- glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3β,12α-diol (HA-3, fuscoineroside C),3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-holosta-9(11)-ene-3β,12α,17α-triol (HA-4, echinoside A), 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4) -β-D-quinovopyranosyl-(1→2)-4-O-sulfato-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3 β,12α,17α-triol ( HA-5, arenicolaside A ), 3-O-[ 3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D- glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sulfato-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3β,12α-diol (HA-6, arenicolaside B), 3-O-[β-D- quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3β,12α,17α-triol (HA -7, holothurin B), 3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-- holosta-9(11)-ene- 3β,12α,17α-triol (HA-8, echinoside B); and four sterols: 3β- sulfato-24-methylenecholest- 5α- cholesta-7( 8 )-ene (HA-9, arenicolaside C), 3β-sulfato-24- methylenecholest-5α-cholesta ( HA-10, arenicolaside D), 3β-sulfato-24-methyl-5α- cholesta- 7,22E-diene (HA-11, arenicolaside E), 3β-sulfato-24-methyl-5α-cholesta-7(8)-ene (HA-12, arenicolaside F).
Eight triterpene glycosides HA-1～HA-8 showed activity against P.oryzae. The preliminary cytotoxic assay of these saponins indicated that BEL-740, HL-60, A-549 and P388. In the anti-fungus screen, eight triterpene glycosides were confirmed active against several fungus lines.
Our studies focused on bioactive constituents of Holothuria arenicola Semper have established a foundation for further research and development of the kind sea cucumber with abundant resources in South China Sea, and provided important leading compounds for the development of new anti-cancer and anti-fungus drugs.
在化学结构测定中,特别采用~1HNMR、~(13)CNMR和二维核磁共振技术(DQCOSY、TOCSY、HMQC、HMBC和NOESY等)和电喷雾离子质谱以及化学方法(水解,化学鉴别),确定了这些化合物的化学结构。其中8个海参皂苷的化学结构为:3-O-[3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α,17α-三醇(HA-1, holothurin A),3-O-[3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-海参烷-9(11)-烯-22-羟基-3β,12α,17α-三醇(HA-2, holothurin A1),3-O-[3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α-二醇(HA-3, fuscoineroside C),3-O-[3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-海参烷-9(11)-烯-3β,12α,17α-三醇(HA-4, echinoside A),3-O-[3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸基-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α,17α-三醇(HA-5, arenicolaside A),3-O-[3-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃奎诺糖-(1→2)-4-O-硫酸基-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α-二醇(HA-6, arenicolaside B),3-O-[β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-22,25-环氧-海参烷-9(11)-烯-3β,12α,17α-三醇(HA-7, holothurin B),3-O-[β-D-吡喃奎诺糖-(1→2)-4-O-硫酸钠-β-D-吡喃木糖]-海参烷-9(11)-烯-3β,12α,17α-三醇(HA-8, echinoside B)。4个甾体化合物:3β-硫酸酯基-24-亚甲基-5α-7(8)-胆甾烯(HA-9,arenicolaside C),3β-硫酸酯基-24-亚甲基-5α-胆甾(HA-10,arenicolaside D),3β-硫酸酯基-24-乙基-5α-7,22E-胆甾二烯(HA-11,arenicolaside E),3β-硫酸酯基-24-乙基-5α-7(8)-胆甾烯(HA-12,arenicolaside F)。其中6个化合物(H A-5、HA-6和HA-9～HA-12)为新化合物。
初步的药理活性筛选表明,海参皂苷HA-1～HA-8,对稻瘟霉显示显著的生物活性,其中HA-1、2和4～6的MMDC值<8μg/ml;对BEL-7402人肝癌细胞、HL-60人白血病细胞、A-549人肺癌细胞和P388小鼠白血病细胞具有较强的细胞毒活性,其中HA-3对BEL-7402人肝癌细胞的抑制率为89.4%(10-6 mol/l),HA-1对A-549人肺癌细胞的抑制率为73.4%(10-8 mol/l);HA-1～HA-8对白色念珠菌、新生隐球菌、克柔式念珠菌、光滑念珠菌和近平滑念珠菌均具有不同强度的抑制生长作用,其中化合物HA-8对白色念珠菌和新生隐球菌的MIC80值达到2.1μg/ml和1.1μg/ml。
本课题首次对蚓参体内的化学成分及药理活性进行了系统的研究,研究结果为进一步研制开发新的抗肿瘤抗真菌药物提供了科学依据和有价值的先导化合物,也为海洋天然产物的研究积累了新的研究资料,对开发利用我国丰富的海参生物资源具有较重要的意义。
Holothuria arenicola Semper distributed abundantly in South China Sea. No chemical works have been performed on this sea cucumber up to date. Guided by Pyricularia oryzae bioassay model, the anti-cancer and anti-fungal constituents of Holothuria arenicola Semper have been investigated by various chromatography methods including LPLC, MPLC, HPLC on silica gel, ODS RP C18 and Zorbax SB C18 respectively. Eighteen compounds were isolated and structures of twelve compounds were elucidated by chemical and spectral analysis (IR, EI-MS, ESI-MS, HRESI-MS, ~1HNMR, ~(13)CNMR, ~1H-1H COSY, DQCOSY, TOCSY, HMQC, HMBC, NOESY, etc.).
From the ethanolic extracts of Holothuria arenicola Semper, twelve compounds were isolated and identified, including eight triterpene glycosides: 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3β,12α,17α-triol (HA-1, holothurin A), 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl- (1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-holosta-22-hydroxyholost-9(11)-ene-3β,12α,17α-triol (HA-2, holothurin A1), 3-O-[3-O-methyl-β-D- glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3β,12α-diol (HA-3, fuscoineroside C),3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-holosta-9(11)-ene-3β,12α,17α-triol (HA-4, echinoside A), 3-O-[3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl-(1→4) -β-D-quinovopyranosyl-(1→2)-4-O-sulfato-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3 β,12α,17α-triol ( HA-5, arenicolaside A ), 3-O-[ 3-O-methyl-β-D-glucopyranosyl-(1→3)-β-D- glucopyranosyl-(1→4)-β-D-quinovopyranosyl-(1→2)-4-O-sulfato-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3β,12α-diol (HA-6, arenicolaside B), 3-O-[β-D- quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-22,25-epoxy-holosta-9(11)-ene-3β,12α,17α-triol (HA -7, holothurin B), 3-O-[β-D-quinovopyranosyl-(1→2)-4-O-sodiumsulfate-β-D-xylopyranosyl]-- holosta-9(11)-ene- 3β,12α,17α-triol (HA-8, echinoside B); and four sterols: 3β- sulfato-24-methylenecholest- 5α- cholesta-7( 8 )-ene (HA-9, arenicolaside C), 3β-sulfato-24- methylenecholest-5α-cholesta ( HA-10, arenicolaside D), 3β-sulfato-24-methyl-5α- cholesta- 7,22E-diene (HA-11, arenicolaside E), 3β-sulfato-24-methyl-5α-cholesta-7(8)-ene (HA-12, arenicolaside F).
Eight triterpene glycosides HA-1～HA-8 showed activity against P.oryzae. The preliminary cytotoxic assay of these saponins indicated that BEL-740, HL-60, A-549 and P388. In the anti-fungus screen, eight triterpene glycosides were confirmed active against several fungus lines.
Our studies focused on bioactive constituents of Holothuria arenicola Semper have established a foundation for further research and development of the kind sea cucumber with abundant resources in South China Sea, and provided important leading compounds for the development of new anti-cancer and anti-fungus drugs.
引文
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[1] For an overview of total syntheses involving the aldol bond formation, see: (a) Mukaiyama, T. Tetrahedron 1999, 55, 8609. 8 (b) Nicolaou, K. C.; Vourloumis, D.; Winssinger, N.; Baran, P. S. Angew. Chem., Int. Ed. 2000, 39, 44. 9
[2] Duthaler, R. O. Angew. Chem. Int. ed. 2003, 42, 975.
[3] (a) Hajos, Z. G.; Parrish, D. R. J. Org. Chem. 1974, 39, 1615. (b) Eder, U.; Sauer, G.; wiechert, R. Angew. Chem., Int. Ed. Engl. 1971, 10, 496.
[4] Cohen, N. Acc. Chem. Res. 1976, 9, 412.
[5] (a) Danishefsky, S.; Cain, P. J. Am. Chem. Soc. 1976, 98, 4975. (b) Kwiatkowski, S.; Syed, A.; Brock, C. P.; Watt, D. S. Synthesis 1989, 818. (c) Ramamurthi, N.; Swaminathan, S. Indian J. Chem., Sect. B 1990, 29, 401. (d) Przezdziecka, A.; Stepanenko, W.; Wicha, J. Tetrahedron: Asymmetry 1999, 10, 1589
[6] (a) List, B.; Lerner, R. A.; Barbas, III, C. F. J. Am. Chem. Soc. 2000, 122, 2395. (b) List, B.; Notz, W. J. Am. Chem. Soc. 2000, 122, 7386. (c) Sakthivel, K.; Notz, W.; Bui, T.; Barbas, III, C. F. J. Am. Chem. Soc. 2001, 123, 5260.
[7] (a) Bahmanyar, S.; Houk, K. N. J. Am. Chem. Soc. 2001, 123, 12911. (b) Rankin, K. N.; Gauld, J. W.; Boyd, R. J. J. Phys. Chem. A 2002, 106, 5155. (c) Domingo, M. A. R. Theor. Chem. Acc. 2002, 108, 232. (d) Hoang, L.; Bahmanyar, S.; Houk, K. N.; List, B. J. Am. Chem. Soc. 2003, 125, 16. (e) Bahmanyar, S.; Houk, K. N.; Martin, H. J.; List, B. J. Am. Chem. Soc. 2003, 125, 2475.
[8] Teck, P. L.; Li, C. F.; Hai, Y. Y.; Jiang, Y. Y.; Tetrahedron Lett. 2002, 43, 8741.
[9] Chandrasekhar, S.; Narsihmulu, C. H.; Reddy, N. R.; Sultana, S. S. Tetrahedron Lett. 2004, 45.
[10] Hayashi, Y.; Tsubo, I. W.; Shoji, M.; Suzuki, N. Tetrahedron Lett. 2004, 45, 4353.
[11] Gruttadauria, M.; Riela, S. R.; Meo, P. L.; Danna, F. R. Tetrahedron Lett. 2004, 45, 6113.
[12] Notz, W.; List, B. J Am Chem Soc. 2000, 122, 7386.
[13] Kitazume, T.; Jiang, Z. J.; Kasai, K.; Miharay.; Suzuki, M. J Fluorine Chem. 2003, 121, 205
[14] Peng, Y. Y.; Ding, Q. P.; Li, Z. C.; Wang, P. G.; Cheng, J. P. Tetrahedron Lett. 2003, 44, 3871.
[15] Storer, R. I.; Macmillan, C. Tetrahedron. 2004, 60, 7705.
[2] 廖玉麟,编著. 中国动物志,棘皮动物门,海参纲 [M]. 北京:科学出版社,1997:108-110.
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[8] 邹峥嵘, 易杨华,李玲等. 海参皂苷的研究进展. 中国海洋药物,2004,23(1): 46-53.
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[1] For an overview of total syntheses involving the aldol bond formation, see: (a) Mukaiyama, T. Tetrahedron 1999, 55, 8609. 8 (b) Nicolaou, K. C.; Vourloumis, D.; Winssinger, N.; Baran, P. S. Angew. Chem., Int. Ed. 2000, 39, 44. 9
[2] Duthaler, R. O. Angew. Chem. Int. ed. 2003, 42, 975.
[3] (a) Hajos, Z. G.; Parrish, D. R. J. Org. Chem. 1974, 39, 1615. (b) Eder, U.; Sauer, G.; wiechert, R. Angew. Chem., Int. Ed. Engl. 1971, 10, 496.
[4] Cohen, N. Acc. Chem. Res. 1976, 9, 412.
[5] (a) Danishefsky, S.; Cain, P. J. Am. Chem. Soc. 1976, 98, 4975. (b) Kwiatkowski, S.; Syed, A.; Brock, C. P.; Watt, D. S. Synthesis 1989, 818. (c) Ramamurthi, N.; Swaminathan, S. Indian J. Chem., Sect. B 1990, 29, 401. (d) Przezdziecka, A.; Stepanenko, W.; Wicha, J. Tetrahedron: Asymmetry 1999, 10, 1589
[6] (a) List, B.; Lerner, R. A.; Barbas, III, C. F. J. Am. Chem. Soc. 2000, 122, 2395. (b) List, B.; Notz, W. J. Am. Chem. Soc. 2000, 122, 7386. (c) Sakthivel, K.; Notz, W.; Bui, T.; Barbas, III, C. F. J. Am. Chem. Soc. 2001, 123, 5260.
[7] (a) Bahmanyar, S.; Houk, K. N. J. Am. Chem. Soc. 2001, 123, 12911. (b) Rankin, K. N.; Gauld, J. W.; Boyd, R. J. J. Phys. Chem. A 2002, 106, 5155. (c) Domingo, M. A. R. Theor. Chem. Acc. 2002, 108, 232. (d) Hoang, L.; Bahmanyar, S.; Houk, K. N.; List, B. J. Am. Chem. Soc. 2003, 125, 16. (e) Bahmanyar, S.; Houk, K. N.; Martin, H. J.; List, B. J. Am. Chem. Soc. 2003, 125, 2475.
[8] Teck, P. L.; Li, C. F.; Hai, Y. Y.; Jiang, Y. Y.; Tetrahedron Lett. 2002, 43, 8741.
[9] Chandrasekhar, S.; Narsihmulu, C. H.; Reddy, N. R.; Sultana, S. S. Tetrahedron Lett. 2004, 45.
[10] Hayashi, Y.; Tsubo, I. W.; Shoji, M.; Suzuki, N. Tetrahedron Lett. 2004, 45, 4353.
[11] Gruttadauria, M.; Riela, S. R.; Meo, P. L.; Danna, F. R. Tetrahedron Lett. 2004, 45, 6113.
[12] Notz, W.; List, B. J Am Chem Soc. 2000, 122, 7386.
[13] Kitazume, T.; Jiang, Z. J.; Kasai, K.; Miharay.; Suzuki, M. J Fluorine Chem. 2003, 121, 205
[14] Peng, Y. Y.; Ding, Q. P.; Li, Z. C.; Wang, P. G.; Cheng, J. P. Tetrahedron Lett. 2003, 44, 3871.
[15] Storer, R. I.; Macmillan, C. Tetrahedron. 2004, 60, 7705.