Synthesis of GDP-Fucose

Wittmann V, Wong C-H (1997) H-Tetrazole as catalyst in phosphomorpholidate coupling reactions efficient synthesis of GDP-fucose, GDP-mannose, and UDP-galactose. J Org Chem 62 2144... 

U. B. Gokhale, O. Hindsgaul, and M. M. Palcic, Chemical synthesis of GDP-fucose analogs and their utilization by the Lewis a-l,4-fucosyltransferase. Can. J. Chem. 65 1063 (1990). 

As indicated in Fig. 8A, in addition to the reactions originating with glucose, alternative pathways exist for the formation of several of the nucleotide sugars directly from their monosaccharide constituents. These reactions may be used for the conversion of dietary monosaccharides, and the contribution by these pathways to the nucleotide sugar pool will be a function largely of the composition of the diet. The utilization of fucose for synthesis of GDP-fucose by this route is catalyzed by fucose kinase and GDP-fucose pyrophosphorylase ... 

A de novo synthesis of GDP-Fuc (13), UDP-Gal (16) and UDP-GalNAc (19) by isolated enzymes of the salvage pathways (see Fig. 14) has not yet been described. A crude extract from porcine submaxillary glands gave a yield of 80% for the synthesis of p-L-fucose-1-phosphate (12), but the synthesis of 13 was less successful with a yield of 20% [312]. The main pathways for 16 and 19 involve 4-epimerases (Table 4 and Fig. 14) which are not suitable for preparative synthesis due to their unfavourable equilibrium constants [347, 348], An alternative is Gal-l-P uridyltransferase which is only specific for Gal-l-P and GalNH2-l-P (Table 4). 

Here again, it is as probes that carba-oligosaccharides find their best applications. Compounds 7 and 8 were both submitted to the action of a-(l-3/4)-fucosyltransferase in the presence of GDP-fucose. Only 7 was accepted and fucosylated to give the Lewis analog 9 showing that this enzyme has a different mode of action regarding the synthesis of Lewis s (Scheme 8.3) [16]. 

Albermann C, Distler J, Piepersberg W. Preparative synthesis of GDP-p-L-fucose by recombinant enzymes from enterobacterial sources. Glycobiology... 

The synthesis of the carba di- and tri-saccharides 103 has been described. and the preparation of carba-disaccharide 104 by a similar process to that reported earlier (Vol. 25, p. 214, ref. 95) has appeared. For the preparation of glycosides of cyclitol derivatives see also Chapter 3. Carbocyclic analogues of GDP fucose have been made as potential inhibitors of fucosyl transferases. ... 

According the synthetic pathway depicted in Scheme 7, a series of non-natural GDP-deoxyfucoses have been prepared successfully (compare Table 2). Hindsgaul and coworkers [67, 68] also reported the synthesis of GDP-Fuc derivatives which bear alkyl chains, aminoalkyl residues capable of being linked to fluorescent labels, and oligosaccharide moieties on the fucose C-6. Siuprisingly, those GDP- fucose derivatives are accepted by certain fucosyl transferases [67, 69]. 

A series of peracetylated fucose analogs have been prepared by the chemical route described for the peracetylated P-fucosyl phosphate (Scheme 7) [87]. Two decisive improvements have been introduced with regard to the fully chemical synthesis of GDP-Fuc (Scheme 13). Firstly, the acetylated fucosyl phosphates used for the coupling reaction are more stable than the unprotected variety and they are far more soluble in the coupling solvent than the unprotected ones. This speeds up the diphosphate formation without any detectable, concomitant anomerization of... 

Wang W, Hu T, Frantom PA, Zheng T, Gerwe B, Del Amo DS, Garret S, Seidel RD HI, Wu P (2009) Chemoenzymatic synthesis of GDP-L-fucose and the Lewis X glycan derivatives. Proc Natl Acad Sci USA 106 16096-16101... 

GDP-ot-D-mannose (23) is the donor substrate for mannosyltransferases [139, 146, 338-340] and the precursor of GDP-(3-L-fucose (13) [173,197, 243, 341], Based on the work of Munch-Petersen [342, 343], only crude extracts from yeast have been used for the enzymatic synthesis of labeled and unlabeled 23 and GDP-deoxymannose derivatives (Table 4) [303-305, 307, 308, 344-346] as well as for the in situ regeneration of 23 (Table 4). Common to all these approaches is the use of chemically synthesized sugar-1-phosphates as substrates for GDP-Man PP. An obvious disadvantage of using crude yeast enzyme preparations is the poor quality of the enzyme source since only fresh cells or certain batches of baker s yeast are suitable for synthesis [304, 307], GDP-Man PP was purified from pig liver and used for the synthesis of 8-Azido-GDP-Man however, the enzyme lacks absolute specificity for GDP-Man in the pyrophos-phorylysis reaction [309]. 

Luengo, J I, Gleason, J G, Synthesis of C-fucopyranosyl analogs of GDP-L-fucose as inhihitors of fucosyltransferases. Tetrahedron Lett., 33, 6911-6914, 1992. 

Cai, S, Stroud, M R, Hakomori, S, Toyokuni, T, Synthesis of carbocyclic analogs of guanosine 5 -(beta-L-fucopyranosyl diphosphate) (GDP-fucose) as potential inhibitors of fucosyltransferases, J. Org. Chem., 57, 6693-6696, 1992. 

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