Natural chemoenzymatic routes

The reactive open-chain substrate 29 with the natural D-threo configuration was prepared along a chemoenzymatic route by making use of the common constitutional and stereochemical relationship which substrates of transaldolase share with those of transketolase. Thus, the R-configured 2-hydroxyaldehyde 28 was chain-extended under transketolase catalysis in the presence of 20 as ketol donor to yield the desired aldol. By this approach, several transaldolases could indeed be shown to display different levels of kinetic stereoselectivity. 

A big factor for the success of the process was the close similarity of the substrate to the natural substrates of Subtilisin Carlsberg, an enzyme with extraordinary properties. Since cheap commercial sources for this enzyme were available on the market, the enzyme could be discarded. A major disadvantage of the present chemoenzymatic route was the fact that no satisfactory racemization procedure for the unwanted enantiomer (R)-2 could be established due to elimination and/or hydrolysis side reactions. 

Chemoenzymatic route for the preparation of the natural alkaloids dihydropinidine (c/s) and ep/-dihydropinidine trans). 

Besides sclareol, the microbial hydroxylation of a number of other naturally found and easily available terpenes of the labdane family has been investigated, particularly in view of designing chemoenzymatic routes for the hemisynthesis of forskolin 25, an activator of adenylate cyclase used as a therapeutic agent, or for the generation of potentially active analogs. Actually, 1,9-dideoxyforskolin 26 invariably co-occurs with forskolin 25... 

Finally, natural (i )-(-)-mevalonolactone, a key intermediate from a broad spectrum of cellular biological processes and their regulation, was synthesised via eight steps in 55% overall yield and > 99% ee (Scheme 19). In the key step, the aforementioned enantioconvergent chemoenzymatic deracemization route was applied. Thus, 2-methyl-2-benzyl-oxirane ( )-2 g was deracemized on a large scale (10 g) using lyophilized cells of Nocardia EHl and sulfuric... 

Biocatalysis is a key route to both natural and non-natural polysaccharide structures. Research in this area is particularly rich and generally involves at least one of the following three synthetic approaches 1) isolated enzyme, 2) whole-cell, and 3) some combination of chemical and enzymatic catalysts (i.e. chemoenzymatic methods) (87-90). Two elegant examples that used cell-fi-ee enzymatic catalysts were described by Makino and Kobayashi (25) and van der Vlist and Loos (27). Indeed, for many years, Kobayashi has pioneered the use of glycosidic hydrolases as catalysts for polymerizations to prepare polysaccharides (88,91). In their paper, Makino and Kobayashi (25) made new monomers and synthesized unnatural hybrid polysaccharides with regio- and stereochemical-control. Van der Vlist and Loos (27) made use of tandem reactions catalyzed by two different enzymes in order to prepare branched amylose. One enzyme catalyzed the synthesis of linear structures (amylose) where the second enzyme introduced branches. In this way, artificial starch can be prepared with controlled quantities of branched regions. 

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