10.1021/acscatal.0c01310
The research describes a novel method for the γ-C(sp3)–H oxygenation of free aliphatic amines, utilizing 2-hydroxynicotinaldehyde as a transient directing group and N-fluoro-2,4,6-trimethylpyridinium tetrafluoroborate as a bystanding oxidant. The purpose of this study was to develop a general protocol for the selective oxygenation at the γ-methyl positions of a wide range of aliphatic amines, which could be coupled with various aryl, heteroaryl, and aliphatic acids, as well as primary, secondary, and tertiary alcohols, to afford amine-containing esters and ethers. The conclusions highlight the method's broad applicability, good functional group tolerance, and its potential for late-stage functionalization of natural products and drug molecules, such as ibuprofen, isozepac, fenbufen, and lithocholic acid. This approach provides a more straightforward access to mono-protected amino alcohols and hindered ethers, which are challenging to synthesize using conventional methods.
10.1016/j.ejmech.2020.112083
Lithocholic acid (LCA) serves as a core structure for the development of EphA2 antagonists. LCA, also known as 5?-cholan-24-oic acid, is a bile acid that has been identified as a weak competitive inhibitor of the EphA2-ephrin-A1 association. The study extends the understanding of structure-activity relationship (SAR) data for two classes of EphA2 antagonists, 5b-cholan-24-oic acids and 5b-cholan-24-oyl L-b-homotryptophan conjugates, leading to the identification of UniPR505 (compound 14) as a potent submicromolar antagonist. This compound effectively blocks EphA2 phosphorylation and inhibits neovascularization in a chorioallantoic membrane (CAM) assay. The study includes detailed chemistry methods for synthesizing the compounds, SAR analysis showing the impact of different substituents on inhibitory potency, molecular modeling to understand the binding mechanism, and biological assays demonstrating the compound's ability to inhibit EphA2 activation and angiogenesis. The findings suggest that UniPR505 is a promising candidate for further development as an antiangiogenic therapy for cancer treatment.
