Stereoselective synthesis of butenolides and its applications in total synthesis of sessilifoliamides and development of new chemical tools for hydrogel based biomaterials

Abstract

The research in my doctoral study consists of two major parts. One part is a synthetic method development and its applications in solving complex synthetic chemistry problems. The other part is a multidisciplinary research involving the collaboration of the Fox group and the Jia group in material science, studying the development of new biomaterials for cell culture purpose. ☐ Butenolides are privileged scaffolds in medicinal chemistry and important synthetic building blocks. Allyl cyclopropene carboxylates undergo ring expansion reaction to give alloxyfuran intermediates, which can further rearrange to Δβ, γ butenolides via Claisen rearrangement or Δα, β butenolides via a further Cope rearrangement. The chemoselectivity and regioselectivity can be controlled through judicious choice of catalyst and reaction temperature. The transformation is stereospecific and transfers the chirality of the allyl cyclopropene carboxylate to the butenolide product. Through assignment of the absolute configuration of the product, it was possible to propose a mechanistic model for the rearrangements. ☐ The second chapter centers on the application of the butenolide formation method described in chapter one towards the total synthesis of sessilifoliamide nature products. The route features a one-step installation of the butenolide moiety to furnish the dehydro-sessilifoliamide from a cyclopropene carboxylate precursor and a short and efficient synthesis of the cyclopropene carboxylate. A short 11-step synthesis of dehydro sessilifoliamide B is described. Attempts to prepare sessilifoliamide B by hydrogenation were unsuccessful. ☐ The third chapter describes a collaborative research on the development of biomaterial for cell culture purpose using tetrazine ligation. The chapter describes the development of chemical tools for the hydrogel preparation. The mechanical properties of hydrogels were controlled by introducing capping groups alongside crosslinker molecules in interfacial crosslinking events. Enzyme degradable crosslinkers and cell adhesive signals are prepared and introduced to the gels. It was shown by my collaborator that all the newly developed chemical tools can be incorporated in to the HA-Tz based hydrogels and NIH 3T3 cells can be cultured in the system with good viability and morphology.