New Fluorous Tags for Combinatorial Synthesis

用于组合合成的新型含氟标签

基本信息

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
项目类别：
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

项目摘要

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有机小分子（候选药物）。溶液相组合化学方法变得越来越重要，氟技术平台是一种新的、强大的补充，可以加速并利用溶液相合成。然而，由于缺乏市售氟标签（保护基团），目前氟合成和氟混合物合成等新技术的应用受到限制，因此迫切需要新的氟标签。该 SBIR 提案通过新氟标签的逐步研究（发现）和开发（验证和扩大规模）过程来满足这一需求。具体目标是： 1) 合成Fmoc（9-芴基甲基氨基甲酸酯）、Cbz（氨基甲酸苄酯）和Bn（苄基）保护基的含氟变体。新的氟标记的设计使得全氟烷基链将控制氟二氧化硅上标记分子的分离特性。可以并入多个亚甲基之一以抵消全氟烷基的电子效应。 2) 验证这些新的氟标签在涉及保护、反应和脱保护的合成序列中的使用。对于每个含氟基团，在选择在保护和脱保护方面能够很好地模拟母体并且在氟二氧化硅上具有合适的分离性能的基团之前，将测试几个候选基团。 3) 优化新氟标签的工艺规模合成并合成同系物。这些新标签的合成将在 100-200 克规模上进行优化。根据需要，该公司将与定制合成公司签订公斤级制备这些新标签的合同。对于这些含氟标签中的每一个，将合成一系列具有可变数量的氟的同系物以用于含氟混合物合成。