Development of chemical and chemo-enzymatic glycosylations

Abstract

Glycosidic compounds are indispensable molecules in living systems. Biological phenomena such as cell wall formation, energy storage, and cell recognition strongly depend on the multi-functional characters of these substances. Development of highly regio- and stereoselective glycosylation reactions is necessary to provide sufficient amounts of specific compounds in basic research as well as for applications in industry. This review presents an overview of chemical and chemo-enzymatic glycosylations that have been developed during my forty-year academic career in the field of glyco-science. In the course of these studies, several new concepts such as “Direct Anomeric Activation”, “Glyco-Process Chemistry” and “Glyco-Chemistry Cycles” have been established.

Structure–function relationship of terpenoid glycosyltransferases from plants

“…Regio- and enantioselective glycosylations in an aqueous environment are chemically very demanding – a reaction that nature has elegantly accomplished with its glycosyltransferases. 147 These enzymes add sugars and sugar chains to chemically highly differentiated molecules in all organisms on earth, from the smallest to the macromolecules including terpenoids. 85 Terpenoids play an important role in the struggle for survival of organisms and are of great economic interest to humans as biological agents, especially because of their glycosides.…”

“…These results and tools will help to adapt and optimize UGTs to terpenoid target substrates by rational protein design and to realize the biotechnological production of terpene glycosides in the near future. 147…”

Glycosynthase Principle Transformed into Biocatalytic Process Technology: Lacto-N-triose II Production with Engineered exo-Hexosaminidase

“…Any viable process technology for biocatalytic glycosylation will involve a matching pair of enzyme and donor substrates which combine to give the reaction efficiency demanded by the processing objective. ,,,, The intrinsic interdependence of enzyme and donor in controlling the reactivity and selectivity of the glycosylation makes their selection a fundamental problem of decisive importance for practical realization. In the case of glycosynthases, therefore, this selection implies a convergent strategy of enzyme engineering and synthetic design of the donor substrate. ,− The high degree of chemical activation necessitated in typical glycosynthase donors renders them labile substrates for biocatalytic transformations. − An enzymatic conversion rate substantially faster than the substrate decomposition rate is therefore required, but this may be difficult to obtain with glycosynthases possessing low specific activity.…”

Sequential acid-catalyzed alkyl glycosylation and oligomerization of unprotected carbohydrates

“…One should mention that enzymatic catalysis potentially paves the way to APGs with larger , but the cost of the enzymes and the low reactor productivity hamper the implementation of these routes on a bigger scale. 18,19,20,21 In this work, we propose an alternative straightforward strategy based on the use of propargyl alcohol (PGA), which serve not only as a glycosyl acceptor but also as a linker to subsequently introduce the fatty chain through a 100% atom economy copper-catalyzed Huisgen reaction. In contrast to fatty alcohols, at the end of the reaction, PGA can be conveniently separated by distillation at a low temperature limiting the degradation of APGs.…”