Glycals monosaccharides

Easily prepared from the appropriate monosaccharide, a glycal is an unsatu-rated sugar with a C1-C2 double bond. To ready it for use in potysaccharide synthesis, the primary -OH group of the glycal is first protected at its primary -OH group by formation of a silvl ether (Section 17.8) and at its two adjacent secondary - OH groups by formation of a cyclic carbonate ester. Then, the protected glycal is epoxidized. 

Glycal assembly method (Section 25.11) A method for linking monosaccharides together to sym thesis polysaccharides. 

Note 1. The term glycal is a non-preferred, trivial name for cyclic enol ether derivatives of sugars having a double bond between carbon atoms 1 and 2 of the ring. It should not be used or modified as a class name for monosaccharide derivatives having a double bond in any other position. 

Our strategy for synthesis of the oligosaccharide chains,27.28 calls for 2,6-dideoxyhexoses or the corresponding glycals to serve as precursors for both a- and p-glycosidation reactions. It a selective p-glycosidation protocol can be developed, then in principle any structural isomer or analogue of the natural product can be assembled from a common set of monosaccharide precursors.29... 

Initially, the de novo synthesis of enantiomerically pure carbohydrates [110] and glycolipids [111] using transition metal complexes and chiral auxiliaries afforded only modest success. Ultimately, it was the use of enantiomerically pure aldehydes, such as the R and S enantiomers of 2-(phenylseleno)propionaldehyde, to convey facial selectivity upon the LACDAC reaction that enabled the synthesis of optically pure glycals. Syntheses of several complex monosaccharides such as the main sialic acid-type N-acetylneuraminic acid (Neu5Ac) and rac-3-deoxy-ma o-2-octulosonic acid (KDO) were accomplished with this technology [112, 113], The LACDAC... 

In this chapter, methods for oxidation, reduction, and deoxygenation of carbohydrates are presented. In most cases, the reactions have been used on aldoses and their derivatives including glycosides, uronic acids, glycals, and other unsaturated monosaccharides. A number of reactions have also been applied to aldonolactones. The methods include both chemical and enzymatic procedures and some of these can be applied for regioselective transformation of unprotected or partially protected carbohydrates. 

Generally two main classes of unsaturated sugars in which (1) the anomeric carbon atom is involved in a double bond (glycals) and (2) the unsaturation is placed between other carbon atoms are known. One has to discuss also derivatives with the exo- and enclo-unsaturated bonds (either oleflns/dienes or acetylenes). Another class of unsaturated monosaccharides is represented by the open-chain sugars with the double bond(s) and/or triple bond present in the molecule. The examples of different types of unsaturated sugars are shown in O Fig. 2. Compounds such as glycals will not be discussed here, unless they are used as substrates for the preparation of other, non-anomeric, unsaturated derivatives. 

Hunt and Roush [60] used a solid phase method to prepare 6-deoxy di- and trisaccharides. A sulfonate linker was employed to coimect the first monosaccharide, a glycal, via its C6 position to the polymer resin. A galactosyl trichloroacetimidate donor was used in the first coupling reaction, followed by cleavage from the solid support by treatment with Nal to furnish pure disaccharides in 85-91% yield. Reduction with BusSnH (AIBN) provided the desired 6-deoxydisaccharide. 

The most straightforward application of the cyclocondensation reactions of aldehydes with activated dienes is in the synthesis of simple monosaccharides.- Condensation of diene (100) with benzyloxyacet-aldehyde (9a) using Bp3-Et02 as a catalyst, followed by treatment with TFA, gives the dihydropyrone (102). Reduction of (102) using DIBAL-H followed by hydroxylation of the glycal gives, after deprotection, talose (103 Scheme 30). 

More complex monosaccharides such as daunosamine and fucose are assembled using a similar strategy (Scheme 31).- - Cyclocondensation of diene (104) with acetaldehyde (9f) using the lanthanide catalyst Eu(hfc)3 gives the syn cycloadduct (105). Treatment of (105) with TFA followed by oxymercuration [Hg(OAc)2-NaCNBH4] and reductive amination of the oxime acetate (derived from the ketone) gives daunosamine (108). Fucose (107) is prepared from compound (106) by reduction of the ketone and treatment of the glycal with MCPBA in methanol. 

Hotha and Tripathi [45] reported a practical method based on microwave irradiation for Perrier reaction of per-O-acetylated glycals 49a,b with primary, secondary, allylic, benzylic, and monosaccharide alcohols they used a catalytic amount of niobium pentachloride to give the corresponding 2,3-unsaturated O-glycosides 51 and 53 with a stereoselectivity in high yields and with short reaction times (Scheme 12.24). 

Condensation of syn- or anti-27 with hydrazine afforded new pyrazole derivatives 28 with a stereodefined and protected amino diol side chain [64]. The preparation of push-pull substituted unsaturated monosaccharide derivatives and their use in the synthesis of nucleoside analogs have been reviewed [65]. Thus, the 2-formyl pentose glycals were transformed to the corresponding acyclo-C-nucleosides 29 [66]. Similarly, the benzy-lated 2-formylglycals reacted with hydrazine derivatives to afford the substituted l,2,4-tri-0-benzyl-lC-(lH-pyrazol-4-yl)-D-tetritols the deprotection of which was achieved with Pd/H2 to yield the lC-( 1-methyl-lH-pyrazol-4-yl)-D-tetritols [67]. 3-0-Benzyl-6-deoxy-l,2-0-isopropylidene-o -D-xylo-hept-5-ulofuranurono-nitrile was reacted with f, N-dimethylformamide dimethyl-acetal in THF to furnish the (E)-3-0-benzyl-6-deoxy-6-dimethyl-aminometh-ylene-l,2-0-isopropylidene-Q -D-xylo-hept-5-ulofuranurono-nitrile as a major product, and on treatment with carbon disulfide and methyl iodide under basic conditions afforded 3-0-benzyl-6-deoxy-l,2-0-isopropylidene-6-[bis(methylsulfanyl)methylene]-a-D-xylo-hept-5-ulofuranurono-nitrile. Further reaction with hydrazines yielded the reversed pyrazole-C-nucleoside analogs [68]. 

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