Studies and Applications of Metals for the Synthesis of Carbinols, Amides and Carbohydrates

The present dissertation describes the research performed at the Technical University of Denmark and at the Institute for Glycomics in the period April 2008 – Oct 2011. The thesis involves four discrete topics related to organometallic and carbohydrate chemistry. Project 1: Ultrafast Grignard addition reactions inthe presence of protic agents The addition of allylmagnesium bromide and benzylmagnesium chloride to carbonyl compounds was studied in the presence of protic agents (e.g. water, methanol, ethanol, phenol).

In a number of cases, especially by the use of allylmagnesium bromide the carbonyl addition was found to be faster or comparable to the protonation by the reagent. Project 2: Ruthenium catalyzed synthesis of amides from primary alcohols and amines The direct synthesis of amides from alcohols and amines with the simultaneous liberation of dihydrogen was previously discovered in the Madsen group.

Further development of the reaction conditions were investigated, in which stoichiometric additives or hydrogen acceptors were not required and the reactions were catalyzed by ruthenium Nheterocyclic carbene complexes. Two catalyst systems were found to be effective promoters for the amidation. These two systems do not show any significant differences in reactivity indicating that the same catalytically active species is operating.

Project 3: Synthesis of a trisaccharide probe as a putative dengue virus receptor At the Institute for Glycomics major research has been devoted to identify putative receptors for dengue virus (DENV). Based on previous studies the GlcNAcß1-3Galß1-4GlcNAc trisaccharide was considered as a putative virus receptor.

The synthesis of the trisaccharide probe has been achieved by the coupling of the corresponding D-glucosamine donor and the lactosamine acceptor, followed by deprotection. The biological investigation is in process. Project 4: Glycosylation with unprotected acceptors Regioselective Koenigs-Knorr glycosylation has been studied with a number of unprotected acceptors by means of organoboron derivatives, which can either activate or block cis-diols via ester formation.

By means of phenylboronic acid high regioselective and stereospecific glycosidic bond formations were achieved.