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.

凭借该奖项，化学系的化学合成项目正在资助奥克兰大学化学系的Nessan J. Kerrigan教授探索开发合成γ-内酯的新方法。 γ-内酯是医学上相关的化合物，是许多生物活性分子（例如抗生素和 HIV-1 抑制剂）的关键成分，并且还具有作为合成其他生物学上感兴趣的分子的管道的潜力。开发天然产物和生物活性合成物中常见的结构基序的制备方法对于制药和生物技术领域的学术和工业部门都具有重要意义。 该项目更广泛的影响还涉及对从本科生到博士后水平的学生的技术培训，包括来自历史上在科学领域代表性不足的群体的学生。正在采取三种不同的策略来开发由亚砜盐形成γ-内酯的反应的对映选择性变体。 目前合成γ-内酯的方法通常具有多步骤方法、有限的底物范围和适度的非对映选择性或对映选择性的特点。 Kerrigan 研究小组开发了一种通过亚砜叶立德、醛和烯酮的反应（“3 组分反应”）非对映选择性合成带有 α-季立体中心的 γ-内酯的方法。它以有趣的 [3,3]-sigmatropic 重排为关键步骤。在该项目下，Kerrigan 研究小组计划探索反应的范围，例如包括检查稳定叶立德、半稳定叶立德和单取代乙烯酮。 Kerrigan 教授的小组正在研究对映体富集的氨基亚砜盐、手性 Koga 胺和手性布朗斯台德酸（手性氢键供体催化剂），以用于γ-内酯形成反应中的不对称诱导。 该项目的成功开发具有提供潜力，因为它提出了高效且廉价地获得许多理想的五元循环合成子的途径。