The Development of Novel Annelation Reactions with Indolidene Intermediates

宾夕法尼亚州立大学的肯·费尔德曼教授正在开发有效的方法来制备人类激素受体结合剂，作为潜在的候选药物。本项目由美国国家科学基金会化学部化学合成项目资助。这些方法是基于费尔德曼博士实验室的初步发现，这些发现涉及将小分子片段缝合在一起，以形成控制分子形状的较大化学结构的新方法。这些产物分子将有助于理解有助于与一种激素受体而不是另一种激素受体选择性结合的结构特征。资助的研究还包括关于海水修复技术的研究，后一项工作的更广泛影响可能包括提高海洋观赏植物的饲养质量。该化学以形成吲哚的新方法为特色，吲哚衍生的活性物种参与键的形成，将五元环或七元环附加到吲哚框架上。由于带附加环的吲哚是药物发现的重要目标，这种化学可能会影响制药科学的几个领域。更具体地说，初步报告将激活人孕激素受体的显著选择性归因于一种附加在吲哚上的五元环，称为Lecanindole D，这是一种自然产生的真菌衍生材料。对这种选择性的结构基础的调查是这项资助研究的主要目的。

Professor Ken Feldman of The Pennsylvania State University is developing efficient methods to prepare human hormone receptor binding agents to serve as potential drug candidates. This project is funded by the Chemical Synthesis program of the Chemistry Division at the National Science Foundation. These methods are based upon preliminary discoveries in Dr. Feldman's laboratory involving new approaches to stitch together small pieces of molecules in order to form larger chemical structures with control over molecular shape. These product molecules will aid in understanding the structural features that contribute to selective association with one hormone receptor over another. The funded research also includes studies on marine water remediation techniques, and the broader impacts of this latter work might include improvements in the quality of husbandry for marine ornamentals. The chemistry features a new approach to forming indolidenes, reactive indole-derived species that engage in bond formation to append either five-membered rings or seven-membered rings onto the indole framework. Since indoles with appended rings constitute important targets for drug discovery, this chemistry may impact several areas of pharmaceutical science. More specifically, preliminary reports ascribe a remarkable selectivity for activating the human progesterone receptor over other hormone receptors by a five-membered ring appended indole called lecanindole D, a naturally occurring fungal-derived material. The investigation of the structural basis for this selectivity is a major thrust of the funded research.