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Development of novel hypervalent iodine reagents and their applications to stereoselective synthesis of biologically active natural products

新型高价碘试剂的开发及其在生物活性天然产物立体选择性合成中的应用

基本信息

批准号：
08457584
负责人：
KITA Yasuyuki
金额：
$ 4.74万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

In this project, we focussed our attention on the development of novel reactions using hypervalent iodine (III) reagents activated by Lewis acids such as BF_3・Et_2O and TMSOTf, and their applications to the synthesis of biologically active natural products.We recently reported the nucleophilic substitution of phenol ethers using phenyliodine (III) bis (trifluoroacetate) (PIFA). The reaction is efficient for the introduction of nitrogen, oxygen, carbon, and sulfur nucleophiles to phenol ethers. In this project, the applications of activated hypervalent iodine reagents to intramolecular cyclization reactions have been developed, which are described below.i) The intramolecular cyclization of phenol ethers bearing an alkyl azide side chain directly gave quinone imine derivatives in good yields using PIFA-TMSOTf. This reaction was also found to be effective for the synthesis of indoloquinone-imines, key precursor to marine anti-tumor alkaloids.ii) The intramolecular phenolic coupling reaction using PIFA-BF_3・Et_2O enabled to synthesize the essential structure of amaryllidaceae alkaloids and multi-functionalized biaryl compounds in good yields.iii) A novel and efficient synthesis of sulfur-containing heterocyclic compounds using PIFA-BF_3・Et_2O from phenol ethers bearing benzylthioalkyl side chain was developed.Furthermore, we found a novel method for alpha-azidation of cyclic sulfides. The combination of Phl=O and TMSN_3 allowed alpha-azidation of dihydrobenzothiophen derivatives, which are easily aromatized and labile under oxidative conditions, in moderate yields. These findings will provide powerful tools for the total synthesis of sulfur-containing discorhabdins.

本项目主要研究了以BF_3·Et_2O和TMSOTf等刘易斯酸为活化剂的高价碘（III）试剂的新反应及其在天然产物合成中的应用，最近报道了苯基碘（III）双（三氟乙酸）（PIFA）与酚醚的亲核取代反应。该反应对于将氮、氧、碳和硫亲核试剂引入苯酚醚是有效的。在本项目中，已经开发了活化的高价碘试剂在分子内环化反应中的应用，其描述如下：i）使用PIFA-TMSOTf，具有烷基叠氮侧链的酚醚的分子内环化直接得到良好产率的醌亚胺衍生物。还发现该反应对于吲哚醌-亚胺的合成是有效的，本文报道了利用PIFA-BF_3·Et_2O分子内酚偶联反应合成石蒜科生物碱和多功能联芳基化合物的新方法，以及利用PIFA-BF_3·Et_2O合成含硫杂环化合物的新方法。2 O的反应，并发现了一种新的环硫醚的α-叠氮化反应方法。Phl=O和TMSN_3的组合允许二氢苯并噻吩衍生物的α-叠氮化，其在氧化条件下容易芳构化且不稳定，产率适中。这些发现将为含硫discorhabdins的全合成提供有力的工具。