Glycosylation with Mannosyl Donors

The synthesis of the tetramannose donor 93 (Scheme 13.13) resembled that of Schmidt s syntheses of yeast GPI and rat brain Thy-1 GPI [44, 53], A series of glycosylations started with the formation of the Man(al- 6) bond between trichloro-acetimidate 34 and 6-alcohol 90 in the presence of TMSOTf. Iterative removal of the 02 protecting group and glycosylations with mannosyl donors 91 and 34 completed the tetramannose 92. To achieve the glycosyl donor 93, the allyl group was removed with PdCl2, followed by trichloroacetimidate formation. 

Glycosylation with Mannosyl Donors Mannosylation using Insoluble Promoters... 

SCHEME 15.7 a-Glycosylation of serine and threonine building blocks with mannosyl donors carrying 0-acetyl participating groups favors formation of an a-mannoside. 

P-Mannosides are difficult to introduce because the axial C-2 substituent of a mannosyl donor sterically and electronically disfavors nucleophilic attack from the P-face. P-Mannosides have been obtained by the direct substitution of a-glycosyl triflates, which are conveniently prepared by the treatment of an anomeric sulfoxide with triflic anhydride (Tf20) or thioglycosides with NIS (Scheme 4.3a)... 

P selectivity. Crich and coworkers proposed that, under preactivation conditions, the oxocarbenium ion is trapped by a triflate anion to form the more stable a-triflate 65. After addition of the acceptor, the a-triflate intermediate can then be displaced in an SN2-like manner to afford a p-mannoside product (68). The formation of a-glycosyl triflates was confirmed by II, 13C, and 19F NMR analyses of the activated mannosyl donor recorded at low temperature [37], The experimentally determined KIE is approximately 1.12, which is consistent with an oxocarbenium-like TS [38], It was hypothesized that the a-triflate converts into the contact ion pair 66 in which the triflate anion remains at the a face or that an exploded TS is formed where the nucleophile is loosely associated with the oxocarbenium ion as the triflate departs [39,40], The a product 69 can be explained by the formation of the solvent-separated ion pair 67 where the counterion is solvated and facial selectivity is lost. 

El Ashry, E S H, Schuerch, C, Synthesis of standardized building-blocks as a (3-D-mannosyl donors with a temporary protection to be 3,6-di-O-glycosyl acceptors, for constructing the inner core of glycoproteins and artificial antigens. Bull. Chem. Soc. Jpn., 59, 1581-1586, 1986. 

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