New Initiators for Stereochemical Control in Polypeptide Synthesis

本研究计划的重点是发现和研究新的金属催化方法，以合成具有独特立体化学和结构的多肽。通过活性中间体的鉴定，阐明了钌/铑/铱偕胺磺酰胺引发α -氨基酸n -羧基氢化物聚合的机理。这些聚合的立体化学选择性的起源将通过研究单体和配体对手性金属活性物质立体化学的影响的动力学来解决。这些发现将指导新的引发剂的开发，从而可以完全控制多肽立体化学，包括形成交替的D/L立体聚合物。在有机和大分子化学项目的支持下，加州大学圣巴巴拉分校化学和材料科学系的Timothy J. Deming教授正在研究多肽合成的新催化技术，为具有独特分子结构的复杂多肽的选择性和高效合成提供了希望。多肽是生物利用的主要大分子之一。这些大分子，由许多氨基酸连接在一起，显示出广泛的重要的物理和化学性质。多肽制备的新方法为高效合成具有新的和/或不寻常性质的分子提供了希望，特别是在开发用于选择性分子转化的新催化剂方面。

This research program focuses on the discovery and study of new metal-catalyzed methods for the synthesis of polypeptides with unique stereochemistry and structure. By identification of active intermediates, the mechanism of ruthenium/rhodium/iridium amido-sulfonamide initiated alpha-amino acid N-carboxyanhydride polymerizations will be elucidated. The origins of the stereochemical selectivity of these polymerizations will be addressed through studies of the dynamics of and monomer and ligand influences on the stereochemistry of the chiral metal active species. These discoveries will then guide the development of new initiators that will allow complete control of polypeptide stereochemistry, including the formation of alternating D/L stereocopolymers.With the support of the Organic and Macromolecular Chemistry Program, Professor Timothy J. Deming, of the Departments of Chemistry and Materials Science at the University of California, Santa Barbara, is studying new catalytic techniques for polypeptide synthesis, offering promise for the selective and efficient synthesis of complex polypeptides with unique molecular architectures. Polypeptides represent one of the major classes of macromolecules utilized by living organisms. These large molecules, comprised of many amino acids linked together, display a wide range of important physical and chemical properties. New approaches to the preparation of polypeptides offer promise for the efficient synthesis of molecules anticipated to display new and/or unusual properties, particularly in the development of new catalysts for selective molecular transformations.