Synthesis of unnatural analogues of pancratistatin and narciclasine

Described herein is the chemoenzymatic synthesis of several different types of unnatural analogues of Amaryllidaceae constituents. Development and refinement of existing and design and execution of new approaches towards the synthesis of C-1 analogues of pancratistatin and A-ring heterocyclic analogues of narciclasine are discussed. Evaluation of the new analogues as cancer growth inhibitory agents is also describe

Characterization of the Dynamic Equilibrium between Closed and Open Forms of the Benzoxaborole Pharmacophore

Benzoxaboroles are a class of five-membered hemiboronic acids that recently attracted significant attention as a new pharmacophore on account of their unique structural and physicochemical properties and their ability to interact selectively with biomolecules. Their structural behavior in water and its effect on their physiological properties remain unclear, especially the question of dynamic hydrolytic equilibrium of the oxaborole ring. Herein, we used NMR spectroscopy, in mixed aqueous-organic solvent, to confirm the strong preference for the closed form of benzoxaborole and its six- and seven-membered homologues over the open boronic acid form. Only with the eight-membered homologue does the cyclic form become unfavorable. Using dynamic VT-NMR studies with designed probe compound <b>20</b>, we demonstrate that the oxaborole ring undergoes rapid hydrolytic ring closing–opening at ambient temperature at a rate of >100 Hz via a mechanism featuring rate-limiting proton-transfer steps. This knowledge can help provide a better understanding of the behavior of benzoxaboroles in biological systems

Self-Healing and Injectable Shear Thinning Hydrogels Based on Dynamic Oxaborole-Diol Covalent Cross-Linking

Hydrogels containing sugar and oxaborole residues with remarkable self-healing properties were synthesized by free-radical polymerization in a facile and one pot process. The strong covalent interactions between the oxaborole residues and free adjacent hydroxyl groups of the pendent sugar residues of the glycopolymer allowed the in situ formation of hydrogels achievable under either neutral or alkaline conditions. These hydrogels showed excellent self-healing and injectability behaviors in aqueous conditions and were found to be responsive to both pH and the presence of free sugars (such as glucose) in solution. Furthermore, these hydrogels can easily be reconstructed from their lyophilized powder into any desired three-dimensional scaffold. Additionally, the hydrogels can be designed to have very low cytotoxicity and hence can be used as a scaffold for cell encapsulation. With these unique properties, these biocompatible, biodegradable, rebuildable, and self-healable hydrogels offer great potential in many biomedical applications.</p

Self-Healing and Injectable Shear Thinning Hydrogels Based on Dynamic Oxaborole-Diol Covalent Cross-Linking

Hydrogels containing sugar and oxaborole residues with remarkable self-healing properties were synthesized by free-radical polymerization in a facile and one pot process. The strong covalent interactions between the oxaborole residues and free adjacent hydroxyl groups of the pendent sugar residues of the glycopolymer allowed the <i>in situ</i> formation of hydrogels achievable under either neutral or alkaline conditions. These hydrogels showed excellent self-healing and injectability behaviors in aqueous conditions and were found to be responsive to both pH and the presence of free sugars (such as glucose) in solution. Furthermore, these hydrogels can easily be reconstructed from their lyophilized powder into any desired three-dimensional scaffold. Additionally, the hydrogels can be designed to have very low cytotoxicity and hence can be used as a scaffold for cell encapsulation. With these unique properties, these biocompatible, biodegradable, rebuildable, and self-healable hydrogels offer great potential in many biomedical applications