Synthetic studies on fatty acid derived natural products with biologically activities

本研究为脂肪酸衍生的具有生物活性的天然产物的合成开发了新的合成方法，实现了以下天然产物的全合成.抗肿瘤番荔枝内酯类化合物的全合成为了构建番荔枝内酯类化合物特有的四氢吡喃（THP）环结构，本文采用SmI_2介导的β-烷氧基丙烯酸酯自由基环化反应，合成了一系列番荔枝内酯类化合物。首先，通过Sm法合成的高度官能化的THP衍生物与γ-内酯之间的Wittig反应完成了麦角碱的全合成。此外，我们还探索了一种构建番荔枝内酯类化合物碳骨架的新方法，发现分子间烯烃复分解反应适合于这种目的。将该方法应用于从阿氏旋毛虫中提取的天然内酯的制备和阿氏旋毛虫素的第二代合成.抗病毒大环内酯的合成研究Macroviracin A具有一个42元的大环内酯核心，核心由一个含有D-葡萄糖残基的C_2脂肪酸二聚体和一个连接在核心上的长侧链组成。<22>组成型脂肪酸衍生物通过由烯烃醇和烯烃羧酸制备的末端烯烃酯的分子内复分解来合成。另一方面，通过末端烯烃酯的分子间复分解反应，一步合成了抗病毒药物的C_2对称大分子二聚体。

We have developed new synthetic methods for the synthesis of fatty-acid derived natural products with biological activities, and achieved total syntheses of natural products as follows.1. Total synthesis of antitumor annonaceous acetogenins.In order to construct a tetrahydropyran (THP) ring that is regard as a characteristic structural feature of several annonaceous acetogenins, a SmI_2 mediated radical cyclization reaction of β-alkoxy acrylate was developed. First total synthesis of pyragonicin was accomplished by the Wittig reaction between a highly functionalized THP derivative synthesized by the Sm method and a γ-lactone. Furthermore a new method for construction of the carbon-backbone of annonaceous acetogenins was searched, and we found that an intermolecular olefin metathesis was suitable for such a purpose. This methodology was applied to preparation of a natural lactone obtained from Trichilia alaussenii and a second-generation synthesis of pyragonicin.2. Synthetic studies on an antiviral macrodiolide, macroviracin A.Macroviracin A bears a 42-membered macrodiolide core consisting of a C_<22> fatty acid dimer possessing D-glucose residues, and a long side chain attached to the core. The constitutive fatty acid derivative was synthesized by an intramolecular metathesis of a terminal olefin ester that was prepared from an olefin alcohol and an olefin carboxylic acid. On the other hand, an intermolecular metathesis of the terminal olefin ester provided the C_2-symmetric macrodiolide core of the antiviral agent in a single step.