RESUMEN
Ketoesterification stands as a pivotal technique in organic synthesis, particularly due to its essential role in the construction of numerous natural products and bioactive compounds. In this study, we have successfully accomplished a visible-light-induced cyclization and diastereoselective direct ketoesterification of cyclohexadienones, facilitating access to cis 6,5-fused tetrahydrobenzofuranone derivatives. The utilization of TEMPO radical quenching experiments has provided insights, suggesting an ionic mechanism underlying this methodology. Additionally, the regioselective addition of 2-oxo-2-phenylacetate to the least hindered side in a cis-selective fashion makes this protocol more appealing toward natural product development. Incorporation of a continuous flow reaction into the batch protocol has notably bolstered the efficiency and reaction rate. Furthermore, the demonstration of gram-scale reactions in the flow setup and synthetic utility with NaOH underscore the scalability and practical applicability of this approach.
RESUMEN
Ascorbic acid (AA) is one of the important biomolecules involved in all phases of wound healing. The aim of this study was to develop a new hydrogel system that offers topical delivery of ascorbic acid to wounds during wound care management. In this work, we grafted poly (ethylene glycol) methacrylate onto a renewable biopolymer gellan, and the graft copolymer (GPMA) formed was crosslinked covalently and ionically, and used as a matrix for delivering AA to the wounds. By the processes of grafting and crosslinking, the mechanical properties of the gellan increased several fold compared to mechanically weak native gellan. In vitro cytotoxicity evaluation showed that GPMA was non-cytotoxic to fibroblast cells. GPMA hydrogel matrix allowed the sustained release of AA. When AA was incorporated in GPMA, a significant improvement in wound closure was observed in scratch wound assay performed with keratinocytes. Since AA acts as a cofactor in collagen synthesis, the controlled delivery of AA to the wound microenvironment favors the up-regulation of colα1 gene expression. This study revealed that ascorbic acid, at a concentration of 150 µM, has a favorable impact on wound healing when tested in vitro. Overall results indicate that the GPMA matrix could be a promising material for wound healing applications.