New Initiators for Stereochemical Control in Polypeptide Synthesis

该研究计划的重点是发现和研究新的金属催化方法，用于合成具有独特立体化学和结构的多肽。通过对活性中间体的鉴定，阐明了钌/铑/铱氨基磺酰胺引发α-氨基酸N-羧酸酐聚合的机理。这些聚合的立体化学选择性的起源将通过研究的动力学和单体和配体的手性金属活性物种的立体化学的影响来解决。这些发现将指导新引发剂的开发，这些引发剂将允许完全控制多肽立体化学，包括交替D/L立体聚合物的形成。在有机和大分子化学计划的支持下，圣巴巴拉的加州大学化学和材料科学系的Timothy J.德明教授正在研究多肽合成的新催化技术，为选择性和有效合成具有独特分子结构的复杂多肽提供了希望。多肽是生物体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组成，显示出广泛的重要物理和化学性质。制备多肽的新方法为有效合成预期显示新的和/或不寻常的性质的分子提供了希望，特别是在用于选择性分子转化的新催化剂的开发中。

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.