New organosulfur-based strategies for efficient and selective organic synthesis.

用于高效和选择性有机合成的新的基于有机硫的策略。

• 批准号: 10427113
• 负责人: Oleg V Larionov
• 金额: $ 28.4万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-05 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10427113
• 关键词: Affect; Agrochemicals; Alkenes; Biological; Boron; Coupling; Development; Drug Design; Drug Prescriptions; Dyes; Exhibits; FDA approved; Goals; Health; Healthcare; Human; Hydrogen Bonding; Lead; Medicine; Methods; Molecular; Natural Products; Nitrogen; Organic Synthesis; Oxygen; Personal Satisfaction; Pharmaceutical Chemistry; Pharmaceutical Preparations; Pharmacologic Substance; Polyenes; Positioning Attribute; Reaction; Reagent; Research; Role; Route; Structure; Sulfinic Acids; Sulfonamides; Sulfones; Sulfur; Synthesis Chemistry; Therapeutic Agents; Transition Elements; Work; base; catalyst; chemical property; diene; drug discovery; functional group; improved; oxidation; programs; small molecule

Organosulfur compounds have a major role in advancing human health and well-being. A quarter of the most prescribed drugs contain sulfur, and sulfur is the most common heteroatom in all approved drugs after oxygen and nitrogen. The sulfur-containing functional groups also enable a variety of reactions that are used to synthesize natural products, biological probes, therapeutic agents, dyes, and advanced functional materials. However, the diverse and pluripotent reactivities of organosulfur compounds lead to low chemo-, regio- and stereoselectivities that adversely affect development of stereo- and regioselective approaches in organic synthesis. The long-term goal of this research is to advance the field of organic synthesis by streamlining synthetic access to centrally important organosulfur compounds and systematically developing their regio- and stereoselective transformations to broad classes of valuable functionalities and structural motifs. The intermediate oxidation state organosulfur reagents sulfinates have the potential to solve limitations of current methods of synthesis of organosulfur compounds and to enable new regio- and stereoselective reactions to a wide range of functionalized small molecules. However, there is a lack of efficient methods of synthesis of sulfinates directly from abundant precursors and a gap in fundamental understanding of the nearly entirely unexplored reactivity of sulfinates in the context of stereoselective C‒C bond forming cross-coupling reactions The overall objective of this research is to develop methods of synthesis of sulfinates from abundant precursors and to develop regio- and stereoselective C−C bond forming reactions of sulfinates. This objective will be accomplished by systematically developing three research topics encompassing currently elusive synthetic methods. In the first part, stereodivergent catalytic cross-coupling reactions of intermediate sulfinates will be developed into a broad synthetic platform to access conjugated dienes and polyenes with high and predictable regio-and stereoselectivity. In the second part, a generic platform for harnessing abundant C−H bonds by means of a regioselective C−H sulfination will be developed. The third part is focused on catalytic alkene sulfination reactions to draw from abundance and reactivity of alkenes. Upon completion of this research program, a broad range of currently synthetically challenging functionalized molecules including sulfur-containing ones will become readily accessible for organic synthesis and drug discovery applications, contributing to improvement of human healthcare through more efficient syntheses of small molecule biological probes and therapeutic agents.

Organosulfur化合物在促进人类健康和福祉方面具有重要作用。最多的四分之一 规定的药物含有硫，硫是氧气后所有认可的药物中最常见的杂原子 和氮。含硫功能组也能够实现多种反应 合成天然产品，生物问题，治疗剂，染料和先进的功能材料。 然而，有机硫化合物的潜水和多能反应性导致化学，区域和 立体选择性对有机的立体和监管方法的发展产生不利影响 合成。这项研究的长期目标是通过简化有机合成领域 合成进入中心重要的有机硫化合物，并系统地开发其区域和区域 对广泛的有价值的功能和结构基序的立体选择性转换。这 中间氧化态有机硫试剂硫酸盐具有解决电流局限性的潜力 有机硫化合物合成的方法，并使新的区域和立体选择反应 广泛的功能化小分子。但是，缺乏有效的合成方法 直接从丰富的前体中硫酸盐，几乎完全理解的基本理解差距 在立体选择性C键形成交叉偶联反应的背景下，硫酸盐的意外反应性 这项研究的总体目的是开发从丰富前体的硫酸盐合成的方法 并发展硫酸盐的区域和立体选择性C-C键反应。这个目标将是 通过系统地开发三个涵盖当前弹性合成的研究主题来完成 方法。在第一部分中，中间硫酸盐的立体催化交叉偶联反应将是 发展成一个广泛的合成平台，以访问具有高且可预测的共轭词典和多元 区域和立体选择性。在第二部分中，通过手段利用丰富的C-H键的通用平台 将开发监管C-H硫酸盐。第三部分集中于催化烯烃硫酸盐 从烯烃的抽象和反应性中得出的反应。该研究计划完成后，一个广泛的 当前合成挑战的功能化分子（包括含硫分子）的范围将 容易获得有机合成和药物发现应用，有助于改进 通过对小分子生物学问题和治疗的更有效合成的人类医疗保健 代理商。

项目成果

Site Reversal in Nucleophilic Addition to 1,2,3-Triazine 1-Oxides.

• DOI: 10.1021/jacs.3c01347
• 发表时间: 2023-06
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Luca De Angelis;Graham C. Haug;G. Rivera;Soumen Biswas;Ammar Al-Sayyed;Hadi D Arman;O. Larionov;M. Doyle

Kinetically-driven reactivity of sulfinylamines enables direct conversion of carboxylic acids to sulfinamides.

• DOI: 10.1039/d3sc04727j
• 发表时间: 2023-11-29
• 期刊: CHEMICAL SCIENCE
• 影响因子: 8.4
• 作者: Dang, Hang T.;Porey, Arka;Nand, Sachchida;Trevino, Ramon;Manning-Lorino, Patrick;Hughes, William B.;Fremin, Seth O.;Thompson, William T.;Dhakal, Shree Krishna;Arman, Hadi D.;Larionov, Oleg V.
• 通讯作者: Larionov, Oleg V.

Catalytic Dienylation: An Emergent Strategy for the Stereoselective Construction of Conjugated Dienes and Polyenes.

催化二烯化：共轭二烯和多烯立体选择性构建的新兴策略。

• DOI: 10.1055/a-1924-2564
• 发表时间: 2023
• 期刊: Synthesis
• 作者: Ahmed,Jasimuddin;Haug,GrahamC;Nguyen,VietD;Porey,Arka;Trevino,Ramon;Larionov,OlegV
• 通讯作者: Larionov,OlegV

Acridine Photocatalysis: Insights into the Mechanism and Development of a Dual-Catalytic Direct Decarboxylative Conjugate Addition

• DOI: 10.1021/acscatal.0c03440
• 发表时间: 2020-10-02
• 期刊: ACS CATALYSIS
• 影响因子: 12.9
• 作者: Dang, Hang T.;Haug, Graham C.;Larionov, Oleg, V
• 通讯作者: Larionov, Oleg, V