New Methods for Stereoselective Addictions to Carbonyls

羰基立体选择性成瘾的新方法

• 批准号: 7127256
• 负责人: TAREK SAMMAKIA
• 金额: $ 26.57万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7127256
• 关键词: Diels Alder reaction; aldehydes; alkyl group; biological products; carbonyl compound; catalyst; chemical addition; chemical synthesis; drug design /synthesis /production; heterocyclic compounds; ketones; reducing agents; stereochemistry

DESCRIPTION (provided by applicant): The aims of this proposal are to discover new reactivity in addition reactions to carbonyl compounds, at times in the context of the total synthesis of natural products. Specific aims include completion of the synthesis of the oxo-polyene macrolide antibiotic RK-397. We have prepared a late stage intermediate and in the next funding period, we will complete this synthesis. We will also study an intramolecular vinylogous aldol reaction similar to the Yamamoto intermolecular vinylogous aldol and we will apply this method to the synthesis of the cytotoxic macrolide, arenolide. We will also study a new strategy for conducting intramolecular aldol reactions based on using C-silylated esters as the nucleophilic component. These compounds are compatible with aldehydes and should react only upon activation. We have also developed an interesting asymmetric O-nucleophilic catalyst for enantioselective acyl transfer in the past funding period. This catalyst currently displays s-values of up to 31 for the methanolysis of alpha-acetoxy N- acylthiazolidinethiones. We will explore this catalyst system in the upcoming funding period and delineate its scope and limitations.

描述（由申请人提供）：本提案的目的是发现羰基化合物加成反应的新反应性，有时在天然产物的全合成背景下。具体目标包括完成氧多烯大环内酯类抗生素RK-397的合成。我们已经准备了一个后期的中间阶段，在下一个资助期，我们将完成这个综合。我们还将研究类似于山本分子间葡萄醛醇的分子内葡萄醛醇反应，并将这种方法应用于细胞毒性大环内酯，烯醇内酯的合成。我们还将研究一种基于c -硅基化酯作为亲核组分进行分子内醛反应的新策略。这些化合物与醛相容，只有在活化后才会发生反应。在过去的资助期内，我们还开发了一种有趣的不对称o亲核催化剂，用于对映选择性酰基转移。该催化剂目前甲醇分解α -乙酰氧基N-酰基噻唑烷硫酮的s值高达31。我们将在即将到来的融资期内探索这种催化剂系统，并描述其范围和局限性。