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: 6853735
• 负责人: Timothy F Jamison
• 金额: $ 20.53万
• 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/6853735
• 关键词: Diels Alder reaction; alkynes; biological products; biotherapeutic agent; chemical synthesis; cyclization; diene; diterpenes; epoxides; method development

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开发几种复杂分子合成的一般策略，使用具有改善人类健康潜力的天然产品来说明每种方法的特点。最近发现的催化环氧化物-炔烃还原偶联用于三种策略中的每一种，用于不同的目的：作为片段偶联，用于从共同的构建块快速组装一系列天然产物(特定目标1)，作为大环化(特定目标2)，以及用于合成用于组装几个二萜类化合物的三环核心的跨环Diels-Alder反应中的立体定义的1，3-二烯(特定目标3)。在具体目标1中，提出了两种互补的方法来合成四种天然产物，即两性内酯T2-T5和与它们结构相关的三个分子。在第一个实验中，由四个简单的构筑块组装而成，并通过三个可能参与这些天然产物生物发生的反应将其转化为本研究中的其他六个目标。另一种策略使用相同的构建块，并直接准备其中四个目标。具体目标2的目标是展示一种策略，在该策略中，催化大环化还安装了在许多有机分子家族中发现的关键官能团阵列。具体目标3描述了开发一种灵活的合成策略来合成胞烷型二萜类化合物，包括诱导神经生长因子合成的芥花碱，以及具有抗菌和抗真菌活性的胞苷、别青素和胞三醇。该策略首先针对两种氰二烯天然产物建立，然后扩展到几种高含氧量的淫羊藿碱、胞苷、别花青素和胞三醇。