Fucosyl Transfer

Starting from achiral materials, two stereoisomeric phosphonylated dihydroxy pyrrolidines (275) and (276), containing four stereogenic centers, have been synthesized enantioselectively, employing a combination of enzymatic and transition-metal-mediated methods. Both compounds contain features of the transition state of the enzyme-catalysed fucosyl transfer reaction and represent building blocks of potential inhibitors against this class of enzymes. The synthesis of new sugar-derived phosphonic acids e.g. (277) from protected... 

Several fucosyltransferases have been isolated and used for in vitro synthesis. The Lewis A al,4-fucosyltransferase transfers unnatural fucose derivatives in from their GDP esters [23]. The enzyme al,3-fiicosyltransferase has been used to L-fucosylate the 3-position of the GlcNAc of A-acetyllactosamine and of sialyl a2,3-N-acetyllactosamine [24]. Several acceptor substrates with modifications in the GlcNAc residue could also be... 

So far, we have never observed, by n.m.r. spectroscopy, oligosaccharides or glycopeptides bearing Fuc and NeuAc both linked to the same N-acetyllactosamine branch this is in agreement with the biosynthetic principle of mutual exclusion existing in transferring (1— 3)-1 inked a-fucosyl and (2— 6)-linked a-sialyl groups to the same N-acetyl lactosamine branch, as formulated by Hill and coworkers.88... 

A number of non-natural fucosyl donors have also been probed with this enzyme [89]. As can be seen from Fig. 12, the C-6-atom of fucose is open for modifications. L-Gal and o-Ara are good substrates, whereas replacement of the 2-OH group of the fucose donor apparently is not tolerated by FucT VI. Indeed, Hindsgaul and coworkers succeeded in attaching the blood group A trisaccharide to the 6-position of the fucose donor and proved the biocatalytic transfer of this strange sugar [90]. The combination of non-natural donors with non-natural acceptors by enzymatic fucosyltransfer has also been probed which proved to be instrumental in the assembly of a library of sialyl-Lewis tetrasaccharides (Fig. 12) [91]. 

The replacement of the N-acetyl group of the N-acetylglucosaniine unit is widely tolerated (Table 9). Especially striking is again the selective fucosylation of the glycuronamide derivatives (entries 11-15). Heterocyclic substituents on the acceptor apparently do not affect the enzyme either (entries 8-10). Nonnatural fucose donors are also recognized by FucT III and transferred in the expected way to form Lewis trisaccharides or sialyl-Lewis tetrasaccharides, respectively (see Fig. 14). 

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