Stereoselective synthesis of butenolides and its applications in total synthesis of sessilifoliamides and development of new chemical tools for hydrogel based biomaterials
Date
2017
Authors
Journal Title
Journal ISSN
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Publisher
University of Delaware
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.
Description
Keywords
Pure sciences, Applied sciences, 3D cell culture, Bioorthogonal reaction, Butenolides, Cyclopropene, Sessilifoliamides