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Organocatalytic Practical Synthesis of Deuterated Building Blocks and Biologically Important Structures

氘代结构单元和生物学重要结构的有机催化实际合成

基本信息

批准号：
9892834
负责人：
WEI WANG
金额：
$ 10万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-10 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9892834
关键词：
Alcohols Aldehydes Alder plant Amines Amino Acids Amino Sugars Ammonium Architecture Aziridines Benzopyrans Biological Biological Process Biomedical Research Boronic Acids Breslow Thickness CD3 Antigens Carbon Dioxide Catalysis Chemicals Chemistry Complex Coupling Decarboxylation Detection Deuterium Development Dyes Electrons Engineering Epoxy Compounds Esters Hydrogen In Situ Iodides Ions Isotopes Kinetics Lead Metabolic Metals Methods Methylation Molecular Organic Synthesis Pathway interactions Pharmaceutical Preparations Positioning Attribute Preparation Process Property Reaction Reagent Research Research Personnel Safety Series Signal Transduction Site Source Structure System Therapeutic Transition Elements Visible Radiation Water adduct carbene catalyst cost cost effective cyclopropane drug discovery fascinate functional group glyoxylic acid improved innovation interest novel nucleophilic addition operation programs quinone methide small molecule tool wasting ylide

项目摘要

Project Summary The frustrating complexity of deuteration chemistry, a very limited number of deuterated building blocks available and high cost of making them hamper access to highly sought deuterated bioactive molecules. Therefore, practical synthesis of versatile deuterated building blocks and `privileged' structures will facilitate the construction of deuterated molecules of interest for their biological studies and drug discovery. We wish to develop a new aminocatalytic activation mode termed `ammonium catalysis' for deuterated molecule synthesis. We challenge the dogma of amine moieties in adducts resulting from nucleophilic additions to iminum ions can serve as leaving groups in ensuing reactions. In situ release of the presumed amine from the addition products will create a new scenario for aminocatalytic direct functionalization of aldehydes. It will be demonstrate that a number of unprecedented efficient catalytic cascade reactions will be realized by the new organic catalysts and new reactivities. These cascade processes produce a fascinating array of highly valued novel complex `privileged' benzopyrans and hydroquinolines with regioselective incorporation of deuterium at metabolically labile sites. In addition, the first binary photo- and organo-catalytic formylation reaction and NHC carbene promoted H/D exchange process with simple non-deuterated aldehydes will be developed for low cost synthesis of fundamentally important deuterated aldehydes and enals. Furthermore, practical chiral amine-catalyzed enantioselective H/D exchange-α-functionalization cascade reactions for synthesis of chiral deuterated highly valued building blocks such as (amino)sugars, amino acids, alcohols, amines etc. will be developed. Finally, new trimethylsulfoxonium iodide promoted CH3/CD3 exchange reactions for synthesis of synthetically and medicinally valued deuterated methyl, cyclopropanes, epoxides, aziridines and therapeutics will be accomplished. These deuterated building blocks and molecular architectures and drugs serve as valuable tools for biomedical researchers to use for biomolecule constructions and biological and drug discovery studies.

项目总结