Glycosyl fluorides condensation reactions

Glycosides may also be prepared by enzyme-catalyzed condensation reactions utilizing a glycosyl fluoride. Thus 6-0-a-maltosylcyclodextrins were prepared enzymically from a-maltosyl fluoride (obtained from the corresponding heptaacetate by Zemplen deacetylation) and cyclodex-trins. " ... 

In this manner, both /3- and a-D-xylosyl fluoride generate a-D-xylose, in the former instance by stereochemical inversion and in the latter by stereochemical retention. The series of events is reflected in each of the inverting glycosidases listed above. The reactions are unique not only because they involve hydrolysis of both (albeit truncated) substrate anomers, but the enzymes also catalyze an uncommon nonhydrolytic condensation reaction using the activated glycosyl fluoride. 

The approach was demonstrated with the following synthesis. Coupling of 1 and 3 affords disaccharide 5 (85%), whereas the reaction of donor 4 with 2 gives the disaccharide 7 (81 %). Disaccharide 5 is treated with 2 to furnish trisaccharide 9 (72 %). The subsequent coupling of 9 with 3 yields tetrasaccha-ride 10 (65 %). Deacetylation of 10 to 11 can be followed by block condensation of trisaccharide 9 with 11, which yields heptasaccha-ride 12 (67 %). Phenylthioglycosides and glycosyl fluorides are used both as donors and as acceptors, and additional steps for activation of the anomeric center are not required in either case. 

Noyori and coworkers found that tetrafluorosilane or trimethylsilyl tri-flate catalyzes the condensation of appropriately protected glycopyranosyl fluorides with trimethylsilyl ethers or alcohols. The strong affinity of silicon for fluorine was considered to be the driving force for this reaction. In the case of Sip4, attack of a nucleophile on the glycosyl cation-SiFj ion-pair intermediate was anticipated. Thus, condensation of 2,3,4,6-tetra-O-benzyl-a- and - -D-glucopyranosyl fluorides (47a and 47fi) with methyl... 

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