Lewis Base Catalyzed Asymmetric Acylation of Nitronates

路易斯碱催化的硝酸盐不对称酰化

• 批准号: 6835785
• 负责人: KEVIN M MCCAULEY
• 金额: $ 2.85万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-02 至 2005-03-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6835785
• 关键词: acylation; catalyst; chemical synthesis; heterocyclic compounds; organic base; postdoctoral investigator; stereochemistry

DESCRIPTION (provided by applicant): Although alpha-nitroketones are versatile synthetic intermediates toward more complex molecules, there are few methods to prepare them. Most methods require multiple steps, and asymmetric syntheses where a chiral quaternary carbon is formed are very rare. Since there is an ever-increasing need to develop asymmetric methodologies toward the synthesis of quaternary carbon centers in natural product and pharmaceutical synthesis, this proposal intends to develop planar chiral heterocycles as Lewis base catalysts to generate quaternary carbon centers via asymmetric acylation of silylnitronates. In addition, a "one-pot" synthesis will be explored where asymmetric acylation occurs after in situ generation of the nitronate. This proposal will investigate the scope of the asymmetric acylation reaction and determine the reaction mechanism and origin of stereochemical control. The products, enantiopure alpha-nitroketones, will be further transformed into alpha-alkyl-alpha-amino acids, which are potent enzymatic inhibitors and are important in investigations on protein structure since they impart conformational constraints.

描述（由申请人提供）：虽然-硝基酮是合成更复杂分子的多功能中间体，但制备方法很少。大多数方法需要多个步骤，而形成手性季碳的不对称合成是非常罕见的。由于在天然产物和药物合成中对季碳中心合成的不对称方法的需求日益增加，本提案拟开发平面手性杂环作为路易斯碱催化剂，通过硅基硝酸钠的不对称酰化生成季碳中心。此外，一个“一锅”合成将被探索，其中不对称酰化发生后，原位生成的硝酸钠。本研究将探讨不对称酰化反应的范围，确定反应机理和立体化学控制的来源。产物，对映纯的α -硝基酮，将进一步转化为α -烷基- α -氨基酸，它们是有效的酶抑制剂，在蛋白质结构的研究中很重要，因为它们具有构象约束。