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Selective Functionalization of Aliphatic Amines - Supplement to Support Mariah Ramos

脂肪胺的选择性官能化 - 支持 Mariah Ramos 的补充

基本信息

批准号：
10798989
负责人：
Tomislav Rovis
金额：
$ 6.97万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2025-03-31
项目状态：
未结题

项目摘要

Principal Investigator: Rovis, Tomislav Abstract Recent years have brought about a greatly enhanced understanding of structure-activity relationships (SARs) of biologically relevant compounds. Accordingly, there is a greater need for streamlined, complementary syntheses to access practical drug scaffolds. Current methods focus on editing the periphery of drug compounds to install versatile functional handles. Alternatively, altering the core of target molecules would provide access to diverse drug scaffolds while leaving peripheral handles untouched. Direct core editing would significantly decrease the design-synthesis-test time, as most drug core alterations require an entirely new synthesis. This proposal describes an efficient synthetic route to access 1,2-diazepines from readily available pyridines through dearomative ring expansion. Aim 1 outlines using previously established methods to obtain the pyridinium ylide intermediate on multi-gram scale, the diazepine can be obtained through a 6π electrocyclic ring opening upon irradiation with 370nm light. 1,2-Diazepines are among the least common nitrogen heterocycles present in FDA approved drugs, likely due to the lack of synthetic pathways that enable access to these scaffolds rather than their biological properties. While pyridine expansions are generally multistep procedures, our work has shown promise for a one-pot route to this expansion product. Additionally, Aims 2 and 3 propose novel, alternate methods of obtaining these valuable products. A one-pot catalytic nitrene transfer with simultaneous irradiation could afford the 1,2 diazepine and variants. Taken together, this proposal provides access to synthetically difficult drug cores, while also introducing synthetic handles for further derivatization. 5

主要研究者：Rovis，Tomislav 摘要近年来，人们对构效关系（SAR）的认识有了很大提高与生物学相关的化合物因此，更需要精简、补充和合成获得实用的药物支架。目前的方法集中在编辑药物的外围，复合物安装多功能手柄。或者，改变靶分子的核心，提供对不同药物支架的访问，同时保持外围手柄不受影响。直接核心编辑将显着减少设计-合成-测试时间，因为大多数药物核心改变需要完全的新合成该建议描述了一种有效的合成路线，以获得1，2-二氮杂卓，通过脱芳扩环得到吡啶类化合物。目标1概述了使用先前建立的以数克规模获得吡啶鎓叶立德中间体的方法，在370 nm光照射下通过6π电环开环。1，2-二氮杂卓是其中之一 FDA批准的药物中存在的最不常见的氮杂环，可能是由于缺乏合成而不是它们的生物学特性。虽然吡啶扩展通常是多步骤的程序，我们的工作已经显示出一个一锅路线的承诺，这膨胀产物此外，目的2和3提出了获得这些有价值的新的替代方法，产品.采用一锅法催化氮烯转移反应，同时辐射，得到1，2-二氮杂卓和变体。总之，该提议提供了合成困难的药物核心的途径，同时还引入合成柄用于进一步衍生化。 5

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Site-Selective α-C-H Functionalization of Trialkylamines via Reversible Hydrogen Atom Transfer Catalysis.

DOI：
10.1021/jacs.1c07144
发表时间：
2021-11-17
期刊：
Journal of the American Chemical Society
影响因子：
15
作者：
Shen Y;Funez-Ardoiz I;Schoenebeck F;Rovis T
通讯作者：
Rovis T

Author Correction: Photoredox catalysis using infrared light via triplet fusion upconversion.

作者更正：使用红外光通过三重态融合上转换进行光氧化还原催化。

DOI：
10.1038/s41586-019-1122-6
发表时间：
2019
期刊：
Nature
影响因子：
64.8
作者：
Ravetz,BenjaminD;Pun,AndrewB;Churchill,EmilyM;Congreve,DanielN;Rovis,Tomislav;Campos,LuisM
通讯作者：
Campos,LuisM

Visible-Light-Controlled Ruthenium-Catalyzed Olefin Metathesis.