Sugar chemo-enzymatic synthesis

To catalyze a protective step in a chemo-enzymatic synthesis of sugar derivatives or of more complex oligosaccharides. 

In other reports, the lipase-catalyzed acylation of benzylidene derivatives of sugars, useful intermediates in the synthesis of oligosaccharides, has been described [42]. For example, the esterification of 4,6-O-benzylidene-a-D-glucopy-ranoside (13) with vinyl acetate by action of Pseudomonas cepacia lipase gave quantitatively the 2-O-acetate 13a. [42b] As a third case, it deserves to be mentioned the extensive work of Russo and coworkers for the chemo-enzymatic synthesis of milk oligosaccharides [43]. 

Scheme 1 Chemical and chemo-enzymatic synthesis of UDP-sugars.

Dihydroxyacetone phosphate-dependent aldolases (DHAP-aldolases) have been used widely for preparative synthesis of monosaccharides and sugar analogs (Fessner and Walter 1997 Wymer and Toone 2000 Silvestri et al. 2003). Among them, RAMA RhuA and FucA from E. coli are the most available aldolases, especially the former which was one of the first to be commercialized (Fessner and Walter 1997 Takayama et al. 1997). In many of the chemo-enzymatic strategies they are involved, the biocatalytic aldol addition to the configuration of the newly stereogenic centers is fixed by the enzyme. However, pertinent examples have been reported in which... 

The delicate nature of the activated donor sugars and the problems encountered with their chemical synthesis prompted glycochemists to investigate preparative alternatives mimicking the in vivo synthesis [30, 71, 72]. The activated donors are obtained either by a combined chemo-enzymatic or a fully enzymatic approach. The individual approach depends on the availability of the required biocatalysts. 

In comparison with the fully chemical synthesis of nucleotide-activated donor sugars the chemo-enzymatic or enzymatic approaches are distinguished by fewer protecting group manipulations and high chemo- and stereoselectivity. This simplifies purification protocols significantly. These features reduce the number of synthetic steps and increase overall yields. 

The fully enzymatic preparation of sugar nucleotides, however, requires the availability of a series of enzymes. In addition, their mutual interactions presupposes exact knowledge of their physiological properties by the user this, in particular, makes chemists hesitate to use biocatalysts. Not all the involved enzymes may tolerate altered, non-natural substrates. A combined chemo-enzymatic approach therefore offers the possibility of combining the advantages of the chemical synthesis and those of the enzymatic preparation, e.g. to prepare non-natural nucleotide activated substrates. 

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