Chemoenzymatic synthesis, sugar

Fig. 39 Chemoenzymatic synthesis of imino sugars exploiting fructose 1,6-diphosppate (FDP) aldolase.

Mostly the baker s yeast transketolase has been used so far to prepare several valuable ketose sugars and derivatives 141 (cf. Sect. 7). Recently, the transketolase was utilized in the key stereogenic transformation of racemic 2-hydroxybutyraldehyde 142 into the homochiral synthon 5,6-dideoxy-D-t/ireo-hexulose 110 for the chemoenzymatic synthesis of (+ )-exo-brevicomin 107 [314], Transketolase has also been applied for the in-situ generation of Ery4P (35) from Fru6P (38) in a multi-enzymatic synthesis of 34 (Scheme 5). 

Scheme 5.19. Chemoenzymatic synthesis of novel cyclic imine sugars. Pase = phosphatase.

Figure 5 (a) Chemoenzymatic synthesis of glycosylated macrocyclic products with DesVii/DesViii. The enzyme system successfuiiy transfers naturai and unnaturai TDP-sugars to C3-OH or C5-OH groups in the naturai and unnaturai agiycone substrates, (b) Two hexaketide NAC thioesters utiiized by DesVii/DesViii as substrates. 

Figure 7 Chemoenzymatic synthesis of macroiactams cataiyzed by Tyc TE. The excised Tyc TE is capabie to produce tyrocidine A (14) with the linear decapeptide NAC thioester or PEGA resin (in blue) with a biomimetic linker. Tyc TE tolerates various modifications to the residues in the rectangle box. However, o-Phe, i-Orn, and i-Leu (in red) are required in all substrates. With modified substrates, Tyc TE generates both macrocyclic peptides with 6-14 amino acids and tyrocidine analogues with different sugar moieties attached to position 4, 5, 6, and 7.

Interaction between the glycoprotein E-selectin (expressed on the surface of endothelial cells) and the sialyl Lewis 1 ligand structures on the surface of neutrophils is a major event in inflammation, infection, and metastasis. Both chemical and enzymatic syntheses have been described for the synthesis of the sialyl Lewisx structure. A summary of the general strategy used in chemoenzymatic synthesis is shown here. Extensive in situ regenerations of the sugar nucleotides are not shown in the scheme.97... 

An interesting feature of the Pasteurella GAG synthases is that they appear to elongate the acceptors in a non-processive fashion in vitro with chain release between sugar addition steps. As noted later, this property facilitates chemoenzymatic synthesis reactions in vitro. 

Polymers from Sugars Chemoenzymatic Synthesis and Polymerization of Vinylethylglucoside... 

C.-H. Wong, Engineering enzymes for chemoenzymatic synthesis. Part I practical routes to aza-sugars and complex carbohydrates. Trends Biotechnol. 10 (1992) 337-341. 

This decarboxylation reaction serves as the tool for enzyme-mediated organic synthesis [136,137]. As seen in Eq. (27), the addition of thiazolium intermediate derived from hy-droxypyruvate proceeds via re face attack to afford the products (76) with stereochemically defined 2,3-erythro stereochemistry. The examples are summarized in Table 7. This method works very well for the synthesis of naturally occurring phosphorylated [126,134], nonphosphorylated ketoses [120,125], and deoxy sugars [115,124]. Moreover, 2,3-erythro-dio motif is exemplified in the chemoenzymatic synthesis of die L-series of aldoses (77-79) [122], aza sugars (80,81) [128-130] and ( )-gjco-brevicomin (69), an insect pheromone [131] (Tab e 8). The stereochemically controlled syntiiesis of aldehydes with d(2) config-... 

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