AMIDES, LACTAMS, AND PEPTIDES VIA NEW TIN (II) AMIDES

通过新酰胺锡 (II) 生成酰胺、内酰胺和肽

• 批准号: 3568426
• 负责人: ERIC J ROSKAMP
• 金额: $ 9.49万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-01 至 1996-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3568426
• 关键词: amides; beta lactam antibiotic; chemical bond; chemical condensation; chemical reaction; drug design /synthesis /production; lactams; method development; peptide chemical synthesis; racemization; tin

DESCRIPTION: The broad, long-term objectives of this proposal are to develop reagents and methods for the synthesis of carbon-nitrogen bonds.The principal investigator seeks to develop new divalent tin amide reagents and then use them to create new methods for making carbon- nitrogen bonds. It is stated that the new methodologies, based on these reagents, will be directed at the preparation of compounds of biological relevance, such as beta-lactams, and peptides. New tin(II) amide reagents are to be prepared via ligand metathesis reactions and characterized to determine their compositions and states of aggregation. These new reagents are to be used to convert esters to amides. The principal investigator also intends to examine the effect ancillary ligands have on the reactivity of tin, the types of amide that can be transferred from tin, and intramolecular amide forming reactions. He is to apply the new methodologies to the preparation of beta-lactams, and peptide linkages, optimizing the yield and determining whether racemization occurs. In particular, he is to examine the fragment condensation approach to peptide synthesis on solid supports. The final amide forming reaction he is to examine involves mixed carboxy amido tin(II) compounds. It is reported that these compounds are readily prepared from Sn(N(SiMe3)2)2, an amine, and a carboxylic acid, and give amides upon warming. The principal investigator is also to apply this methodology to the preparation of amides, lactams, and peptides.

描述：本提案的广泛、长期目标是 开发碳氮合成试剂和方法 债券。首席研究员寻求开发新的二价锡酰胺 然后用它们来创造新的方法来制造碳- 氮键 据指出，新的方法，根据这些 试剂，将直接在生物化合物的制备 相关性，如β-内酰胺和肽。 通过配体复分解反应制备新的氨基锡试剂 反应和表征，以确定其组成和状态 聚合的。 这些新试剂将用于将酯转化为 酰胺。 首席研究员还打算检查 辅助配体对锡的反应性的影响， 可以从锡转移，和分子内酰胺形成反应。 他将把新方法应用于β-内酰胺的制备， 和肽连接，优化产率并确定是否 发生外消旋化。 特别是他要检查 在固体支持物上的肽合成的缩合方法。 他要研究的最后一个酰胺形成反应涉及混合羧基 氨基锡（II）化合物。 据悉，这些化合物是 由Sn（N（SiMe 3）2）2、胺和羧酸容易地制备， 并在加热时产生酰胺。 首席研究员还将 将该方法应用于酰胺、内酰胺和 缩氨酸