New Fluorous Tags for Combinatorial Synthesis

用于组合合成的新型含氟标签

• 批准号: 6549582
• 负责人: Marvin S Yu
• 金额: $ 10万
• 依托单位: FLUOROUS TECHNOLOGIES, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-05 至 2003-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6549582
• 关键词: biotechnology; carbamates; chemical synthesis; combinatorial chemistry; fluorescent dye /probe; technology /technique development

DESCRIPTION (provided by applicant): Modem drug development relies on the rapid synthesis of small organic molecules (drug candidates) by using combinatorial chemistry methods. Solution phase combinatorial chemistry methods are increasingly important, and the fluorous technology platform is a new and powerful addition that both expedites and leverages solution phase synthesis. However, the utility of new techniques like fluorous synthesis and fluorous mixture synthesis is currently limited by the dearth of commercially available fluorous tags (protecting groups), so new fluorous tags are urgently needed. This SBIR proposal addresses this need through a stepwise process of research (discovery) and development (validation and scale up) of new fluorous tags. The specific aims are: 1) To synthesize fluorous variants of Fmoc (9-fluorenylmethylcarbamate), Cbz (benzyl carbamate) and Bn (benzyl) protecting groups. The new fluorous tags are designed such that the perfluoroalkyl chains will control the separation properties of tagged molecules on fluorous silica. One of more methylene groups may be incroporated to offset the electronic effect of the periluoroalkyl groups. 2) To validate the use of these new fluorous tags in a synthetic sequence involving protection, reaction and deprotection. For each fluorous group, several candidates will be tested prior to selecting the one(s) that mimics the parent well in protection and deprotection and have suitable separation properties on fluorous silica. 3) To optimize process scale syntheses of the new fluorous tags and to synthesize homologs. The synthesis of these new tags will be optimized on 100-200 gram scale. As needed, the company will contract for the kg scale preparation of these new tags with custom synthesis companies. For each of these fluorous tags, a series of homologs with variable number of fluorines will be synthesized for the use in fluorous mixture synthesis.

描述（由申请人提供）：现代药物开发依赖于使用组合化学方法快速合成小有机分子（候选药物）。固相组合化学方法越来越重要，而含氟技术平台是一个新的强大的补充，既加快了和利用了固相合成。然而，目前市面上可获得的含氟标签（保护基团）的缺乏限制了氟合成和含氟混合物合成等新技术的应用，因此迫切需要新的含氟标签。本SBIR提案通过新的含氟标签的研究（发现）和开发（验证和扩大规模）的逐步过程来解决这一需求。具体目标是：

项目成果

Fluorous parallel synthesis of a hydantoin/thiohydantoin library.

乙内酰脲/硫代乙内酰脲文库的氟平行合成。

• DOI: 10.1007/s11030-005-1293-y
• 发表时间: 2005
• 期刊: Molecular diversity
• 影响因子: 3.8
• 作者: Lu,Yimin;Zhang,Wei
• 通讯作者: Zhang,Wei