Jacobsen, Eric N.Mayfield, Andrew Beckmann2019-08-082019-032019-01-202019Mayfield, Andrew Beckmann. 2019. Multifunctional Hydrogen-Bond-Donor Catalysts for Selective Furanosylation. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.http://nrs.harvard.edu/urn-3:HUL.InstRepos:41121310Hydrogen-bond-donor catalysts are applied to the construction of challenging 1,2-cis glycosidic linkages of arabinose and other furanose sugars. Identification of an unusual dialkylphosphate leaving group enables preparation of anomerically-pure furanoside substrates suitable for use in a stereospecific glycosylation method. Based on previous glycosylation studies performed in the Jacobsen lab, we propose that hydrogen-bond-donor catalysts promote stereospecificity through concomitant nucleophile- and electrophile-activation. This stereospecific glycosylation method enables synthetic access to diverse furanose linkages in high anomeric ratios. Catalyst-promoted anomerization of the substrate is identified as a major factor leading to the formation of the undesired minor glycoside product. Multifunctional activation in hydrogen-bond-donor catalysis is further examined from a fundamental perspective in transesterification reactions promoted by trifunctional ureas designed to mimic mechanistic features of serine proteases. The importance of the hydrogen-bond donor to catalytic activity in these reactions is quantified, and the mechanistic role of the hydrogen-bond-donor is evaluated.application/pdfenOrganocatalysisGlycosylationFuranosesHydrogen-Bond-DonorsThesis or Dissertation2019-08-08