Sustainable methods for the synthesis of medicinal compounds

药物化合物合成的可持续方法

• 批准号: 8015743
• 负责人: Stacey E Brenner-Moyer
• 金额: $ 11.78万
• 依托单位: BROOKLYN COLLEGE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8015743
• 关键词: Alkenes; Amination; Benign; Carbon; Chemicals; Data; Development; Effectiveness; Environment; Fluorine; Fostering; Funding; Future; Goals; Health; Human; Laboratories; Medicine; Methods; Mission; Nitrogen; Outcome; Outcomes Research; Oxygen; Pharmaceutical Preparations; Process; Productivity; Publishing; Reaction; Reporting; Research; Research Personnel; Resources; Scheme; Solutions; Sustainable Development; System; Testing; Therapeutic; Training; Work; base; catalyst; chemical reaction; drug development; fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether; improved; innovation; novel; programs; small molecule; success; tetrahydrofuran

DESCRIPTION (provided by applicant): The development of sustainable treatments for human illnesses is one of the foremost challenges of the present day. While organocatalytic reactions are a potential means to this end, there is a need to develop organocatalytic reactions with tangible applications as drug development processes. The long-term goal of this research program is to demonstrate the effectiveness of organocatalytic reactions in the synthesis of small molecules that treat illnesses in humans. The overall objective of this application, which is fundamental to ultimately achieving this long-term goal, is to develop organocatalytic reactions that generate products with broad utility in the synthesis of therapeutic compounds. There are two central hypotheses that underlie the proposed research: 1) organocatalytic 2-carbon-heteroatom bond-forming reactions and organocatalytic 1- carbon-heteroatom bond-forming reactions can be combined as new organocascade reactions, and 2)) organocascade reactions can be adapted to produce useful heterocycles. The rationale for the proposed research is that once organocatalytic reactions generate synthetic building blocks of therapeutic compounds, they can be exploited in the synthesis of therapeutic compounds. As this research proposes new methods to be employed in the synthesis of compounds that can improve human health, it is relevant to the NIH's mission of fostering the development and application of new strategies for improving health. The above hypotheses were based on preliminary data from our laboratories and are a feasible extension of published data, and will be tested by two specific aims: 1) Develop organocatalytic carbon-nitrogen bond-forming reactions that generate useful synthons; and 2) Develop novel organocatalytic oxa-Michael additions. For both aims, catalysts and substrates will be synthesized, and starting with conditions reported for the closest relevant examples, reaction conditions will be systematically optimized to achieve efficient transformations. The proposed research is innovative, because it entails the development of organocatalytic transformations that represent new, improved methods for accessing important substructures of medicinal compounds. This is significant because it will establish the viability of organocatalytic reactions as economical, environmentally friendly drug development processes, which are vital to sustaining human health. PUBLIC HEALTH RELEVANCE: The proposed research aims to develop new chemical reactions that can be used in the synthesis of medicines and that employ catalysts that are inexpensive and environmentally benign. The proposed chemical reactions are thus a means of realizing sustainable treatments for human illnesses.

描述（由申请人提供）：开发人类疾病的可持续疗法是当今最重要的挑战之一。虽然有机催化反应是达到此目的的潜在手段，但需要开发具有作为药物开发过程的实际应用的有机催化反应。该研究计划的长期目标是证明有机催化反应在合成治疗人类疾病的小分子中的有效性。该应用的总体目标是最终实现这一长期目标的基础，即开发有机催化反应，产生在治疗化合物合成中具有广泛用途的产品。该研究有两个中心假设：1）有机催化2-碳杂原子成键反应和有机催化1-碳杂原子成键反应可以组合为新的有机级联反应，2））有机级联反应可以适应产生有用的杂环。这项研究的基本原理是，一旦有机催化反应产生治疗化合物的合成构件，它们就可以用于治疗化合物的合成。由于这项研究提出了用于合成可改善人类健康的化合物的新方法，因此它与 NIH 促进改善健康新策略的开发和应用的使命相关。上述假设基于我们实验室的初步数据，是已发表数据的可行扩展，并将通过两个具体目标进行测试：1）开发产生有用合成子的有机催化碳氮键形成反应； 2) 开发新型有机催化氧杂迈克尔加成物。为了这两个目标，将合成催化剂和底物，并从最接近的相关示例报告的条件开始，系统地优化反应条件以实现有效的转化。拟议的研究具有创新性，因为它需要开发有机催化转化，代表了获取药物化合物重要子结构的新的、改进的方法。这很重要，因为它将确立有机催化反应作为经济、环境友好的药物开发过程的可行性，这对于维持人类健康至关重要。 公共健康相关性：拟议的研究旨在开发可用于药物合成的新化学反应，并采用廉价且环境友好的催化剂。因此，所提出的化学反应是实现人类疾病可持续治疗的一种手段。