Lars Kröger

Convenient Multigram Scale Glycosylations of Scented Alcohols Employing Phase‐Transfer Reactions

Various conditions for glycosylation (Koenigs–Knorr, Helferich, trichloroacetimidate, Fischer–Raske, phase‐transfer methods) of 3‐ethoxy‐4‐hydroxybenzaldehyde (ethyl vanillin), 3‐hydroxy‐2‐methyl‐4‐pyranone (maltol) and 2,5‐dimethyl‐4‐hydroxy‐3(2H)‐furanone (furaneol®) were evaluated, taking into account yields and ease of preparation (e.g., utilized donor, catalyst, conditions). The best results were achieved employing phase transfer catalysis in a two‐phase solvent mixture. To increase water solubility for better applicability, the hitherto unknown maltosides of the corresponding alcohols were synthesized, again proving the value of phase‐transfer conditions for glycosylation of phenols. †Dedicated to Professor Dr. Peter Welzel on the occasion of his 65th birthday.

Facile One‐Step Syntheses of Modified O‐Glycoprotein Galβ1‐3GalNAc Structures by Transglycosylation Employing Three β‐Galactosidases from Bovine Testes, Xanthomonas manihotis, and Bacillus circulans *

Natural O‐glycoproteins such as the Thomsen‐Friedenreich antigen or gangliosides contain the motif Galβ1‐3GalNAc as an important disaccharide with significant biologic activity. The arrangement of spatial functionalities in this structure are of particular interest with regard to the development of potential leads en route to pharmaceuticals. Therefore, it was desired to obtain access to a range of modified derivatives of the aforementioned motif paying particular attention to introducing specific deoxy functions instead of hydroxyl groups. *This paper is dedicated to Prof. Rosa M. de Lederkremer, Buenos Aires, on the occasion of her 70th anniversary in recognition of her substantial contributions to carbohydrate chemistry.

On Resin Modification of Monosaccharides

Ellmans dihydropyran resin was used for selective protection of monosaccharide thioglycosides and glycosides. Following on‐resin acylation and subsequent cleavage of the polymer‐bound intermediates, product components having selectively unblocked hydroxyl functions could be obtained.

Transglycosylations employing recombinant α- and β-galactosidases and novel donor substrates

Recombinant α- and β-galactosidases could be prepared in larger amounts for chemoenzymatic syntheses of glycosylated oligosaccharides relevant in nutrition approaches. α-Galactosidase RafA from Escherichia coli, another thermophilic α-galactosidase AgaB from Geobacillus stearothermophilus KVE39, and also a thermophilic β-galactosidase BglT from Thermus thermophilus TH 125 could be employed in α- and in β-glycosylations, respectively. With model structures as well as sucrose, isomaltitol, and isomaltulose the stereo- and regiospecificities were studied. Further, a number of modified donor structures with structural variation and different leaving groups were synthesized, employed, and compared to classical donors for these transglycosylations.

Comparative solution and solid-phase glycosylations toward a disaccharide library

A comparative study on solution-phase and solid-phase oligosaccharide synthesis was performed. A 16-member library containing all regioisomers of Glc-Glc, Glc-Gal, Gal-Glc, and Gal-Gal disaccharides was synthesized both in solution and on solid phase. The various reaction conditions for different approaches and corresponding yields are analyzed and discussed.

Solid-Phase Random Glycosylation

Two different approaches were employed to study solid phase random glycosylations to obtain oligosaccharide libraries. In approach I, Wang resin esters were attached to the acceptors structures. Following their glycosylation and resin cleavage, the peracetylated components of the oligosaccharide libraries were characterized. In approach II, polymer-linked donor components could be employed and processed correspondingly. Approach I proved to be superior regarding yield and versatility of products and also allowed the formation of higher oligomers.

Some findings in transgalactosylations employing modified donor substrates

The scope of transgalactosylation with β-galactosidase (bovine testis) was studied employing a series of modified donor substrates based on p-nitrophenyl β-D-galactopyranoside and as uniform acceptor allyl 2-N-acetamido-2-deoxy-α-D-galactopyranoside. Structurally diverse donor molecules were recognized by the enzyme and led to novel disaccharide components, yet an excessive structural distortion was not accepted.