UDE COBRE: STRAINED MOLECULES FOR SYNTHESIS OF UNNATURAL AMINO ACIDS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 项目三：狐狸 本研究的目的是开发立体和对映体选择性的方法来使用环丙烯和双环丁烷来制备小环类似氨基酸。环丙基和环丁基氨基酸具有重要的生物医学应用，应在蛋白质设计中得到应用。然而，现有的合成方法只能获得有限范围的官能团和取代模式。这一新方法对健康相关科学的国家利益具有重要意义，因为目前的技术水平不允许轻松或多样化地制备小环氨基酸。因此，这项提案的具体目标是发展以下内容： (1)铜催化环丙烯碳金属化反应的一般方法。 (2)将环丙基阴离子从目标1转化为环丙基胺的步骤。 (3)允许将生物相关的官能团结合到这些支架中的方法。 (4)不对称合成环丙烯的对映选择性去质子化路线。 (5)(1)的对映选择性版本及其在合成和环丙基氨基酸中的应用。 (6)将富含对映体的环丙烯转化为双环丁烷，然后转化为环丁烷氨基酸衍生物的方案。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Project III: Fox The aim of this research program is to develop stereo- and enantioselective methods for using cyclopropenes and bicyclobutanes to prepare small ring analogs amino acids. Cyclopropyl and cyclobutyl amino acids have important biomedical applications and should find application in protein design. However, the existing synthetic methods give access to a limited range of functional groups and substitution patterns. The new approach is of significance to national interests in the health related sciences because the current state of the art does not permit small ring amino acids to be prepared easily or in variety. Accordingly, the specific aims of this proposal are to develop the following: (1) general methods for the Cu-catalyzed carbometallation reactions of cyclopropenes that proceed with either syn or anti selectivity. (2) procedures that convert the cyclopropyl anions from Aim 1 to cyclopropyl amines. (3) methodology that permits the incorporation of biologically relevant functional groups into these scaffolds. (4) an enantioselective deprotonation route for the asymmetric synthesis of cyclopropenes. (5) an enantioselective version of (1) and application to the synthesis and cyclopropyl amino acids. (6) protocols that convert enantiomerically enriched cyclopropenes to bicyclobutanes, and subsequently to cyclobutane amino acid derivatives.