海洋生物碱Pityriacitrin及其衍生物的合成与生物活性研究.doc

文档介绍：海洋生物碱Pityriacitrin及其衍生物的合成与生物活性研究
张朴永,孙小飞,万升标,任素梅,江涛*
中国海洋大学医药学院,教育部海洋药物重点实验室,青岛,中国
摘要:目的本文对源自海洋细菌的β-咔啉生物碱Pityriacitrin的全合成与体外细胞毒性进行了描述,其衍生物的合成也是首次报道。方法使用色氨酸或五位被取代的色氨酸与5-取代吲哚作为起始原料,通过改进的Pictet–Spengler反应合成了Pityriacitrin及其衍生物。结果所有化合物均通过红外、核磁共振氢谱、核磁共振碳谱和质谱进行了结构表征。对肿瘤细胞MDA-231进行了体外的细胞毒性测试,其中化合物5显示对MDA-231具有高活性(IC50 = uM)。结论β-咔啉生物碱Pityriacitrin是一个结构新颖的具有抗肿瘤活性的先导化合物,所使用的全合成的反应路线为以后类似物的合成提供了良好的借鉴。
关键词:Pityriacitrin;β-咔啉;抗肿瘤;全合成;海洋生物碱;Pictet–Spengler反应
Synthesis and Bioactivity of the Marine Alkaloid Pityriacitrin and Its Derivatives
Puyong Zhang, Xiaofei Sun, Sumei Ren, Shengbiao Wan, Tao Jiang*,
College of Medicine and Pharmacy, Key Laboratory of Marine Drugs,Ministry of Education, Ocean University of China, Qingdao, China
ABSTRACT:OBJECTIVE Total chemical synthesis and in vitro cytotoxic evaluation of β-carboline alkaloid pityriacitrin, originally isolated from a marine bacterium, and its derivatives is reported for the first time. METHODS Using tryptophan or 5-hydroxyl tryptophan and 5-substituted indole as starting materials, via the modified Pictet–Spengler reaction, pityriacitrin and its derivatives were synthesized. RESULTS pounds have been characterized by IR, NMR and mass spectrometry. All pounds were tested for in vitro cytotoxicity against MDA-231. Compound 5 exhibited high cytotoxicity (IC50 = uM) against MDA-231 cell line. CONCLUSION β-carboline alkaloi