UDE COBRE: STRAINED MOLECULES FOR SYNTHESIS OF UNNATURAL AMINO ACIDS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 项目三：福克斯 本研究计划的目的是发展立体和对映选择性的方法，使用环丙烯和双环丁烷制备小环类似物氨基酸。环丙基和环丁基氨基酸具有重要的生物医学应用，应该在蛋白质设计中找到应用。 然而，现有的合成方法提供了有限范围的官能团和取代模式。这种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容易地或以多种方式制备小环氨基酸。 因此，本提案的具体目标是： (1)环丙烯的铜催化的碳代甲烷化反应的一般方法，其以顺式或反式选择性进行。 (2)将来自目标1的环丙基阴离子转化为环丙胺的方法。 (3)该方法允许将生物学相关的官能团并入这些支架中。 (4)一种不对称合成环丙烯的对映选择性去质子化路线。 (5)（1）的对映选择性形式及其在合成环丙基氨基酸中的应用。 (6)将对映体富集的环丙烯转化为双环丁烷，随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.