Pulverolide是源自云南野生黄粉末牛肝菌（Pulveroboletus Ravenelii）的活性成分之一，其结构新颖，对α-氨基-3-羟基-5-甲基-异恶唑丙酸受体（AMPAR）有较好的激动作用，具有潜在药物的特性，但目前尚未对其进行过系统的研究。本项目拟在前期全合成和活性研究工作的基础上开展：（1）空间位阻与电子效应对aldol反应的作用机制和酸碱同时催化微波辅助酚醚化脱水关环反应的反应机理研究，解决前期全合成收率偏低的问题，进而建立有效、稳定的构建该类骨架化合物的方法；（2）利用药物先导化合物优化原理对其进行结构修饰，通过体外（脑片膜片钳记录）、体内（Mirros水迷宫实验结合开野实验）活性筛选实验，深入探讨构效关系，为发现新型AMPAR调节剂或激动剂先导化合物提供理论支持。

Pulverolide, a new macrofungi bioactive compound with a rare skeleton isolated from Pulveroboltus ravenelii in Yunnan province, poses potentiating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activity and reveals the properties as potential drugs, which had not been systematically studied yet. On the basis of previous research，which accomplished the total synthesis and bioactivity testing，this programme is focus on two aspects. First, to clarify the aldol reaction mechanisms via investigating the infulence of steric hindrance and electronic effect and the role of acid-base catalyst in dehydration-cyclization reaction though microwave-assisted, is approach to improve the yield in total synthesis and to construct the methodology for effective synthesis of pulverolide analogue. Second, the analogues of pulverolide have been screened for positive modulation of AMPAR by in vitro (using brain piece of patch clamp record technology) and in vivo (using Morris water maze to combine open field test) methods, after chemical structural modification of pulverolide applied to hit-to-lead optimization. On the basis of bioactivity results, the structure-activity relationship can be discussed. This research will provide theoretical support for finding a new class of potentiating AMPAR agents.