The Total Synthesis of Thapsigargin

毒胡萝卜素的全合成

• 批准号: 5449385
• 负责人: Dr. Frank Georg Wierschem
• 金额: --
• 依托单位: Yusuf Hamied Department of Chemistry
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2005
• 资助国家: 德国
• 起止时间: 2004-12-31 至 无数据
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/5449385?language=en
• 关键词: Total; Synthesis; Thapsigargin

The focus of our investigation is the first total syntheses of Annomuricin C and E, members of the Annonaceous acetogenin family. The Annonaceous acetogenins, which were only isolated from the plant family Annonaceae, are promising new antitumor and pesticidal agents. These natural products of diverse, but still closely related compounds exhibit a broad range of potent biological activities in a widespread area of interests, such as in vivo antitumor activity and cytotoxic, antibacterial, antimalarial, antiparasitic, immunosuppressive and pesticidal effects. The Annonaceous acetogenins have emerged as promising new leads against the resistance of multidrug resistant tumors and of pesticide resistant insects. Our specific interest in Annomuricin C and E is based on the fact, that these natural products show cytotoxicities against sic types of human tumors, with selectivities to the pancreatic carcinoma (PACA-2) and colon adenocarcinoma (HT-29) cell lines. Annomuricin C as well as Annomuricin E with their characteristic central 2,5-disubstituted, a, a'-dihydroxylated mono-THF moiety are representatives of the most important subclass of the mono-THF acetogenins. The intended synthetic strategy utilizes and develops innovative and efficient synthetic methodologies as well as reagents established by the Ley group to achieve a general synthetic and above all modular approach towards this important subgroup of the Annonaceous acetogenin family. As the use of the BDA protecting group renders for example the enantiopure synthesis of the central 2,5-disubstituted THF moiety, the application of a variety of polymer supported reagents, e.g. PSP, PS-triphenylphosphine, etc. will reduce the number of purification procedures to guarantee straight forward and efficient enantioselective total syntheses of Annomuricin C and E based on a modular synthetic strategy.

我们的研究重点是番荔枝内酯家族成员番荔枝素C和E的首次全合成。番荔枝内酯类化合物是从番荔枝科植物中分离得到的一类新型抗肿瘤和杀虫活性物质。这些不同但仍然密切相关的化合物的天然产物在广泛的感兴趣领域中表现出广泛的有效生物活性，例如体内抗肿瘤活性和细胞毒性、抗菌、抗疟疾、抗寄生虫、免疫抑制和杀虫作用。番荔枝内酯类化合物已成为对抗多药耐药肿瘤和杀虫剂耐药昆虫的有希望的新先导化合物。我们对安诺霉素C和E的特殊兴趣是基于这样的事实，即这些天然产物显示出对人类肿瘤的细胞毒性，对胰腺癌（PACA-2）和结肠腺癌（HT-29）细胞系具有选择性。具有其特征性中心2，5-二取代的，α，α ′-二羟基化的单-THF部分的安诺霉素C以及安诺霉素E是单-THF乙酸配基的最重要亚类的代表。预期的合成策略利用和开发创新和有效的合成方法以及由Ley组建立的试剂，以实现对番荔枝内酯家族的这一重要亚组的一般合成和最重要的模块化方法。由于BDA保护基的使用使得例如中心2，5-二取代的THF部分的对映体纯合成，因此各种聚合物负载的试剂例如PSP、PS-三苯基膦等的应用将减少纯化程序的数量，以保证基于模块化合成策略的安诺霉素C和E的直接和有效的对映体选择性全合成。