Carbohydrates 1,2-hydroxyl groups, protecting group

Methods now available for the partial protection of carbohydrate hydroxyl groups by alkylation are critically evaluated. Of the numerous alkyl protecting groups known, only those widely used in synthetic chemistry of saccharides are discussed. Benzyl, allyl, triphenylmethyl and other arylalkyl ethers, trimethylsilyl, rer/-butyidimethylsilyi, and rm-butyldiphenylsilyl ethers are the main topics of the article. 

The benzyloxycarbonyl group (Cbz or Z) is useful in carbohydrate syuithesis, not only for IV-protection of amino sugars, but also to protect alcohols [262,263]. The main advantage of this group is that it is cleaved by hydrogenolysis, and when compared to benzyl ethers, benzyl carbonates are not only removed more readily [264] but also allow hydroxyl group protection under softer conditions than those employed for benzylation. 

Carbohydrate hydroxyl groups are alkylated in three contexts analysis of polysaccharide sequences, dealt with in Section 4.2.1 protection of OH groups during synthetic transformations, which requires the alkyl residues to be removable and the modification of cheap polysaccharides, such as starch and cellulose, for more desirable properties. 

Other reactions of carbohydrates include those of alcohols, carboxylic acids, and their derivatives. Alkylation of carbohydrate hydroxyl groups leads to ethers. Acylation of their hydroxyl groups produces esters. Alkylation and acylation reactions are sometimes used to protect carbohydrate hydroxyl groups from reaction while a transformation occurs elsewhere. Hydrolysis reactions are involved in converting ester and lactone derivatives of carbohydrates back to their polyhydroxy form. Enolization of aldehydes and ketones leads to epimerization and interconversion of aldoses and ketoses. Addition reactions of aldehydes and ketones are useful, too, such as the addition of ammonia derivatives in osazone formation, and of cyanide in the Kiliani-Fischer synthesis. Hydrolysis of nitriles from the Kiliani-Fischer synthesis leads to carboxylic acids. 

We shall describe a specific synthetic example for each protective group given above. Regiosdective proteaion is generally only possible if there are hydroxyl groups of different sterical hindrance (prim < sec < tert equatorial < axial). Acetylation has usually been effected with acetic anhydride. The acetylation of less reactive hydroxyl groups is catalyzed by DMAP (see p.l44f.). Acetates are stable toward oxidation with chromium trioxide in pyridine and have been used, for example, for protection of steroids (H.J.E. Loewenthal, 1959), carbohydrates (M.L. Wolfrom, 1963 J.M. Williams, 1967), and nucleosides (A.M. Micbelson, 1963). The most common deacetylation procedures are ammonolysis with NH in CH OH and methanolysis with KjCO, or sodium methoxide. 

Some of the original work in the carbohydrate area in particular reveals extensive protection of carbonyl and hydroxyl groups. For example, a cyclic diacetonide of glucose was selectively cleaved to the monoacetonide. A summary describes the selective protection of primary and secondary hydroxyl groups in a synthesis of gentiobiose, carried out in the 1870s, as triphenylmethyl ethers. 

CH2(OMe)2, CH2 = CHCH2SiMe3, MeaSiOTf, P2O5, 93-99% yield." This method was used to protect the 2 -OH of ribonucleosides and deoxyribo-nucleosides as well as the hydroxyl groups of several other carbohydrates bearing functionality such as esters, amides, and acetonides. 

Bu2SnO, benzene BnBr, DMF, heat, 80% yield. This method has also been used to protect selectively the anomeric hydroxyl in a carbohydrate derivative. The replacement of Bu2SnO with Bu2Sn(OMe)2 improves the process procedurally. The use of stannylene acetals for the regioselective manipulation of hydroxyl groups has been reviewed. ... 

Carbohydrate-coupling or glycosylation, is a major synthesis method in carbohydrate preparation. Silver silicates and Ag(I)-exchanged zeolite A - so-called insoluble Ag(I) - have been advocated as promoting agents, applied in more than stoichiometric amount (Fig. 9). All hydroxyl groups except the attacking one are suitably protected. 

The presence in carbohydrates of multiple hydroxyl groups of similar reactivity makes the chemo- and regio-selective manipulation frequently required quite difficult. For this reason, multistep protection-deprotection approaches are regularly employed in carbohydrate chemistry, and versatile techniques for these transformations are particularly helpful. The following section addresses this aspect, concentrating on the catalytic procedures that have been developed employing zeolites and related siliceous materials. 

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