Asymmetric Synthesis of Gamma-Lactones from Sulfoxonium salts.

从磺鎓盐不对称合成γ-内酯。

• 批准号: 1463728
• 负责人: Roman Dembinski
• 金额: $ 30万
• 依托单位: Oakland University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-15 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1463728&HistoricalAwards=false
• 关键词: Asymmetric; Synthesis; Gamma; Lactones; Sulfoxonium

With this award, the Chemical Synthesis Program of the Division of Chemistry is funding Professor Nessan J. Kerrigan of the Department of Chemistry at Oakland University to explore the development of new methods for the synthesis of gamma-lactones. Gamma-lactones are medicinally relevant compounds, acting as key constituents of many biologically active molecules (e.g., antibiotics and HIV-1 inhibitors) and also with the potential to function as conduits for the synthesis of other biologically interesting molecules. The development of methods to prepare structural motifs commonly found in natural products and biological active synthetics has great importance for both the academic and the industrial sectors, both in pharma and in biotechnology. The broader impacts of this project also involve technical training of students, from the undergraduate to post-doctoral levels, including those from groups historically underrepresented in the sciences.Three different strategies are being pursued for the development of enantioselective variants of gamma-lactone forming reactions from sulfoxonium salts. Current methods for the synthesis of gamma-lactones are often characterized by multistep approaches, limited substrate scope, and modest diastereoselectivity or enantioselectivity. The Kerrigan research group has developed a method for the diastereoselective synthesis of gamma-lactones bearing an alpha-quaternary stereogenic center, through the reaction of sulfoxonium ylides, aldehydes and ketenes (the ?3-component reaction?). It features an interesting [3,3]-sigmatropic rearrangement as the key step. Under this project, the Kerrigan research team plans to explore the scope of the reaction e.g., including an examination of stabilized ylides, semi-stabilized ylides, and monosubstituted ketenes. Professor Kerrigan's group is investigating enantioenriched aminosulfoxonium salts, chiral Koga amines, and chiral Bronsted acids (chiral hydrogen bond donor catalysts) for asymmetric induction in the gamma-lactone-forming reactions. Successful development of the project has the potential to provide as it proposes efficient and inexpensive access to a number of desirable 5-membered cyclic synthons.

有了这个奖项，化学系的化学合成计划正在资助奥克兰大学化学系的Nessan J. Kerrigan教授，以探索合成γ-内酯的新方法的发展。 γ-内酯是医学上相关的化合物，作为许多生物活性分子的关键成分（例如，抗生素和HIV-1抑制剂），并且还具有作为用于合成其他生物学上感兴趣的分子的管道的潜力。开发制备天然产物和生物活性合成物中常见的结构基序的方法对于制药和生物技术的学术和工业部门都具有重要意义。 该项目的更广泛影响还涉及对学生的技术培训，从本科生到博士后，包括那些来自历史上在科学领域代表性不足的群体的学生。 目前用于合成γ-内酯的方法通常以多步骤方法、有限的底物范围和适度的非对映选择性或对映选择性为特征。Kerrigan研究小组开发了一种非对映选择性合成带有α-季立体异构中心的γ-内酯的方法，该方法通过氧化锍叶立德、醛和烯酮的反应（该方法？3-成分反应？）。它的特点是一个有趣的[3，3]-sigmatropic重排的关键步骤。在这个项目下，Kerrigan研究小组计划探索反应的范围，例如，包括对稳定化叶立德、半稳定化叶立德和单取代烯酮的研究。 Kerrigan教授的小组正在研究对映体富集的氨基氧化锍盐、手性古贺胺和手性布朗斯台德酸（手性氢键供体催化剂）在γ-内酯形成反应中的不对称诱导。 该项目的成功开发有可能提供，因为它提出了有效和廉价的获得一些理想的5元环状双炔酮。