Generation of Stereochemically and Structurally Complex*

立体化学和结构复杂的生成*

• 批准号: 7125570
• 负责人: JOHN A PORCO
• 金额: $ 40.38万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-23 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125570
• 关键词: Internet; NIH Roadmap Initiative tag; chemical registry /resource; chemical structure; chemical synthesis; cheminformatics; combinatorial chemistry; stereochemistry

DESCRIPTION (provided by applicant): The rapid assembly of complex molecules continues to be of great interest in diversity-oriented synthesis (DOS) as a means to discover novel chemotypes and pharmacological tools. Synthesis of chemical libraries in this manner has employed both stereochemical and skeletal diversity. A distinct approach to obtain molecules with novel pharmacological properties involves library synthesis based on various core scaffolds derived from natural products. This proposal outlines specific plans for a Pilot Libraries (P41) initiative to generate a number of stereochemically and structurally complex chemical libraries for inclusion in the National Institutes of Health (NIH) Molecular Repository. Five library projects are planned reflecting the Principal Investigator's (PI's) and Co-Principal Investigators' (Co-PIs') continued interest in the design of natural product-like molecules using stereochemical and positional variation within the molecular framework. A total of 16 complex libraries are outlined which are distinct from ongoing and planned Center for Chemical Methodology and Library Development (CMLD-BU) library projects. Target pilot libraries include complex dihydropyrimidones, azaphilone-derived libraries, tetracyclic alkaloid-type libraries, exo-methylene scaffolds and derived spirocycles, and macrocyclic lactam frameworks. In addition, all planned libraries have been designed to include unique structures that do not overlap in chemical space with molecules currently in the PubChem database. In order to facilitate synthesis and timely delivery of libraries to the NIH repository, emphasis has been placed on utilization of chemistries previously established in the Pi's and co-PIs' laboratories. A central mechanism for data sharing for the Pilot Library initiative involves using an internet-based structure-searchable database of synthesis protocols. Inclusion of the target libraries that will be developed in this effort in the NIH repository is anticipated to facilitate discovery of new pharmacological tools for investigation of cellular processes.

描述（由申请人提供）：复杂分子的快速组装作为发现新化学型和药理学工具的一种手段，在多样性导向合成（DOS）中继续引起极大兴趣。以这种方式合成化学文库利用了立体化学和骨架多样性。获得具有新药理学性质的分子的独特方法涉及基于源自天然产物的各种核心支架的文库合成。该提案概述了试点图书馆（P41）倡议的具体计划，以产生一些立体化学和结构复杂的化学图书馆，纳入美国国立卫生研究院（NIH）分子库。五个图书馆项目的计划反映了主要研究者（PI）和共同主要研究者（Co-PI）的持续兴趣，在设计天然产物样分子使用立体化学和位置变化的分子框架内。总共有16个复杂的图书馆，这是从正在进行的和计划中的化学方法和图书馆发展中心（CMLD-BU）图书馆项目不同。靶先导文库包括复杂的二氢嘧啶酮、氮杂菲酮衍生的文库、四环类生物碱型文库、外亚甲基支架和衍生的螺环和大环内酰胺框架。此外，所有计划中的文库都被设计为包括在化学空间中与PubChem数据库中的分子不重叠的独特结构。为了便于综合和及时向NIH资料库提供文库，重点放在利用PI和共同PI实验室先前建立的化学品上。试点图书馆倡议的一个数据共享中心机制涉及使用一个基于互联网的合成协议结构搜索数据库。将在NIH储存库中开发的目标库包括在内，预计将有助于发现用于研究细胞过程的新药理学工具。