天然药物化学第十一章天然药物的开发课件

1、第十一章 天然药物的研究开发芳香性：醌、苯丙素、黄酮非芳香性：糖、萜、甾体不含氮含氮: 生物碱天然药物主要来源：生物碱，萜，皂苷一. 内容总论各论提取分离结构测定生物合成天然药物R&D绪论THE CONTINUING NEED FOR DRUG DISCOVERYExpanding global populationBiodiversity is decreasingDrug Resistance is increasingNew diseases are emerging (e.g. SARS)BUT - the cost to market a new drug is increasing

2、 now at least $700 millionAND - the role of natural products as pharmaceuticals is well-establishedPharmaceutical companies are looking for enhanced chemical (structural) diversityNATURAL PRODUCTS AS PHARMACEUTICALSONeill and Lewis (1993) - over 50% of leading Compounds were nat. prod. based.Newman

3、et al. (2003) - between 1981 2002: 340 (39%) of the 868 New Chemical Entities (NCEs) were nat. prod. or nat. prod. based-J. Nat. Prod. 2003, 66, 1022. Over 80% of worlds population use plants as a primary health care source$4.2 Billion on phytotherapeuticals in U.S. in 1999中药现代化基础：文献资料，民间用药经验 手段：生物活

4、性测试（高通量筛选），提取分离技术对象：天然产物：陆地，海洋；动植物（中药），微 生物，矿物内容：分离，结构测定（波谱技术结合化学方法）, 理化性质，半合成，全合成，结构改造（组合化学）目的：发现新的先导化合物或药物 利用和改善药物来源 创制新的药物二. 学科 定义：基础 手段 对象 内容 目的 涉及学科治疗的目标 寻找先导化合物 优化先导化合物 研制侯选药物 新药1. “当归芦荟丸”(11味) 青黛 靛玉红 合成 靛玉红 (Indirubin)靛兰 (Indigotin)治疗慢性粒细胞白血病青蒿素氢化青蒿素还原青蒿素蒿甲醚还原青蒿素琥珀酸钠Anticancer agentsR = H 喜树碱(camptothecine)R = OH 10-羟基喜树碱(hydroxycamptothecine)珙桐科植物喜树(Camptotheca acuminata)治疗多种恶性肿瘤:骨癌、肝癌、膀胱癌和白血病副作用: 骨髓抑制、呕吐和腹泻 水溶性差伊立替康(irinotecan)R1 =R3 = EtR2 = H拓扑替康(topotecan)R1 =