Synthetic Strategies Based on Epoxide Coupling Reactions

基于环氧化物偶联反应的合成策略

• 批准号: 7338666
• 负责人: Timothy F Jamison
• 金额: $ 19.33万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-17 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7338666
• 关键词: Alder plant; Alkynes; Anti-Bacterial Agents; Antifungal Agents; Biogenesis; Biological Factors; Complex; Coupling; Development; Diels Alder reaction; Diterpenes; Epoxy Compounds; Facility Construction Funding Category; Family; Goals; Health; Human; Hydrogen; Nerve Growth Factors; Purpose; Reaction; Research Personnel; Side; Staging; base; catalyst; cyathins; cycloaddition; diene; epimerization; functional group; gloeosporone; improved; muscone; programs

DESCRIPTION (provided by applicant): The overall goal of this project is the development of several general strategies of complex molecule synthesis, using natural products that have the potential to improve human health to illustrate the features of each of these approaches. A recently discovered catalytic epoxide-alkyne reductive coupling is used in each of the three strategies for a different purpose: as a fragment coupling for rapid assembly of a family of natural products from common building blocks (Specific Aim 1), as a macrocyclization (Specific Aim 2), and for the synthesis of stereodefined 1,3-dienes used in transannular Diels-Alder reactions that assemble the tricyclic core of several diterpenoids (Specific Aim 3). In Specific Aim 1, two complementary approaches are presented for the synthesis of four natural products, amphidinolides T2-T5 and three molecules structurally related to them. In the first, amphidinolides T1 and "pseudo-T1" are assembled from four simple building blocks and converted to the other six targets in this study by way of three reactions that may be involved in the biogenesis of these natural products. An alternative strategy uses the same building blocks and prepares four of the targets directly. The goal of Specific Aim 2 is the demonstration of a strategy in which a catalytic macrocyclization also installs a critical functional group array found in many families of organic molecules. Specific Aim 3 describes the development of a flexible synthetic strategy for the cyatane-type diterpenes, including the erinacines, which induce the synthesis of nerve growth factor, and the cyathins, allocyathins, and cyathatriols, which possess antibacterial and antifungal activity. The strategy is first established for two cyathadiene natural products and then extended to several highly oxygenated erinacines, cyathins, allocyathins, and cyathatriols.

描述（由申请人提供）：该项目的总体目标是制定复杂分子合成的几种一般策略，使用具有改善人类健康的天然产品来说明每种方法的特征。 A recently discovered catalytic epoxide-alkyne reductive coupling is used in each of the three strategies for a different purpose: as a fragment coupling for rapid assembly of a family of natural products from common building blocks (Specific Aim 1), as a macrocyclization (Specific Aim 2), and for the synthesis of stereodefined 1,3-dienes used in transannular Diels-Alder reactions that assemble the tricyclic core在几种二萜（特定目标3）中。在特定的目标1中，提出了两种互补方法，用于合成四种天然产物，即两栖类T2-T5和与它们结构相关的三个分子。首先，在这项研究中，通过四个简单的构建块组装了两栖类T1和“伪-T1”，并通过三种反应转换为其他六个靶标，这些反应可能与这些天然产物的生物发生有关。另一种策略使用相同的构件，并直接准备四个目标。特定目标2的目的是演示策略，在这种策略中，催化大环化还安装了许多有机分子家族中发现的关键功能组阵列。具体目的3描述了为蛋白烷类二萜的柔性合成策略的发展，其中包括诱导神经生长因子的合成以及具有抗体和抗真菌活性的cyathins，cyathins，cyatothin和cyathatriols。该策略首先是针对两种cyathadiene天然产物建立的，然后扩展到几种高度氧化的erinacines，cyathins，andocyathins和cyathatriols。