Glucals, epoxidation

Starting from 3,4,6-tri-O-benzyl-D-glucal epoxide 93 (Scheme 31), a-C-glycosyl compounds 94 are obtained in good stereoselectivity by treatment with a lithium acetylide and zinc chloride.103... 

In addition, Wipf and co-workers104 have used silver(i)-catalyzed addition of zirconocenes to 3,4,6-tri-O-benzyl-D-glucal epoxide 93 for the stereoselective synthesis of a-C-glucosyl compounds 95 and 96 following a similar mechanism as in the reaction with organoaluminium and organoboron reagents (Scheme 32). 

Alternatively, pyranosyl radicals can be generated through the reduction of 3,4,6-tri-O-benzyl glucal epoxide with Cp2TiCl2 and manganese metal.136 With the conformationally restricted 1-phenylseleno-D-xylose derivatives 151 and 152 (4Ci conformation) their reaction with Bu3SnCH2 CH=CH2 in the presence of AIBN (Scheme 51) affords the corresponding a-C-pyranosyl derivatives (153) preferentially.137... 

A further route to P-mannopyranosides involves use of the 1,2-anhydride 33, made by the Danishefsky method from tri-O-benzyl-D-glucal. Epoxide ring opening with alcohols in the presence of zinc chloride gives P-glucosides which, by oxidation and reduction, lead to the P-mannosides including P-mannosyl disaccharides. Danishefsky has also adapted compound 33 for use as a precursor of a-glucosides. Treated with tributylstannylated alochols in the presence... 

If k2 > kj, the glycosyl-enzyme intermediate will accumulate, and may be trapped by the rapid denaturation of the enzyme in the presence of (saturating) amounts of substrate. With -glucoside Aj from Asp. wentii and 4-nitrophenyl [ C]-2-deoxy-) -D-irra />jo-hexopyranoside, it was possible to identify the intermediate as a glycosyl ester (acylal) of 2-deoxy-D-arabino-hexose bound to the same aspartate residue that had previously been labeled with the active-site-directed inhibitor conduritol B epoxide and with D-glucal." This constituted an important proof that the carboxylate reacting with the epoxide is directly involved in catalysis. 

Polymer-supported glucal 37 was converted to the protected thioethyl glucosyl donor 39 as outlined in Scheme 2.11. Compound 37 was first epoxidized by the action of DMDO. The resulting 1,2-anhydrosugar was opened by a mixture of ethanethiol and dichloromethane (1 1) in the presence of a trace of trifluoroacetic acid. Polymer-bound 38 was thus obtained in 91% yield. This was a substantial improvement over the 78% yield obtained by the same protocol in solution. Protection by reaction with pivaloyl chloride occurred in quantitative yield to furnish 39a. 

The first problem to be addressed in the solid-phase assembly of Leb involved the synthesis of the core tetrasaccharide (Scheme 2.17).25 Polymer-bound galactal 10 was epoxidized with DMDO. The resultant epoxide reacted with a solution of glucal 55 to give polymer-bound disaccharide diol 56. This reaction proceeded in a highly regioselective fashion, wherein glycosylation occurred only at the allylic C3 position... 

The galactosyl glycal 72 was bound to solid phase via a silyl ether linker. Epoxidation of the glycal using 2,2-dimethyldioxirane and subsequent electrophilic activation of the epoxide resulted in the glycosylation of 3,4-di-O-benzyl glucal 73. After acetylation of the product, the polymer-linked trisaccharide 74 was obtained. 

G. Lauer and F. Oberdorfer, A simple route from glucal to Cerny epoxides, Angew. Chem., Int. Ed., 32 (1993) 272-273. 

The alternative compound 17, with the nucleophile placed at the C-4 position, was prepared hy the same method [19] from regioisomeric (to Cemy epoxide) oxirane 18, which was obtained from D-glucal by iodocyclization followed by standard reactions (O Scheme 7). 

Glycosyl phosphates, building blocks in automated solid-phase synthesis of complex oligosaccharides, were prepared via a 1,2-epoxide (O Scheme 13). Oxidation of the appropriately substituted D-glucal 28 with DMDO followed by reaction with dialkyl phosphate provided the -phosphate 33, which anomerized further to the a-analog [31]. 

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