Carbohydrates hydroxy group protection

Furthermore, superhydride is used as an alternative to LAH in the reduction of carbohydrate epoxides (equation 18), In this example, the C—O bond away from the hydroxy group is selectively cleaved, but a tosyloxy group is also reduced in epoxides having a hydroxy group protected with tosyl. A kinetic study of reductions with superhydride has been reported. ... 

Oxidation of carbohydrate deriratwes. Oxidation of partially acetylated carbohydrates with the reagent of Parikh and Doering leads to both oxidation and elimination of the elements of acetic acid, and thus provides a high-yield route to novel unsaturated carbohydrates.3 Apparently the oxidation step is followed by spontaneous elimination of a /f-acctoxy group. Hydroxy groups protected by benzyl or trimethylsilyl groups are not eliminated. 

Treatment with DBU (1 to 2.5% solution in DMF or DMA) can cause succinimide formation from cyclization of aspartyl residues [77] (Fig. 8) and decomposition when silyl-based groups are used for the protection of carbohydrate hydroxy groups [78]. 

As they are available from natural sources in enantiomerically pure form, carbohydrates are useful starting materials for syntheses of enantiomerically pure compounds. However, the multiple hydroxy groups require versatile methods for selective protection, reaction, and deprotection. Show how appropriate manipulation of protecting groups and/or selective reagents could be used to effect the following transformations. 

Partially protected carbohydrates can be selectively oxidized at the primary hydroxy group to uronic acids at the nickel hydroxide electrode. At the same electrode, in polyhydroxy steroids, a preferential oxidation of the sterically better accessible hydroxyl groups is achieved [142]. By way of the mediator, TEMPO, carbohydrates that are only protected at the anomeric hydroxyl group are selectively oxidized at the primary hydroxyl group (Fig. 27) [143-145]. 

In carbohydrates a hydroxy group may be differentiated from others by appropriate protective group manipulations and then, after tosylation or mesylation, submitted to a SN2-displacement reaction with a nitrogen or sulfur nucleophile. 

The hydroxy group is far more reactive to (dialkylamino)trifluoro-A4-sulfanes than most other functional groups. Thus, at low temperatures a hydroxy group can be selectively fluorinated in the presence of another functional group. This, coupled with the inertness of (dialkylamino)-trifluoro-A4-sulfanes towards most protection groups, and the mild reaction conditions required has enabled a vast array of functionalized fluorinated compounds to be synthesized, for example, carbohydrates,24-29,31 nucleosides,30 and steroids32 35 (see Table 3). 

Derivatives of ortho-nitrobenzyl alcohol were also used to protect the hydroxy groups of carbohydrates, including in the anomeric position. Thus, the following acetal was quantitatively photolysed to glucose (Scheme 13.5) [27]. 

Amino-type groups are also present in carbohydrate molecules although the number is usually much fewer than that of the hydroxy groups. Selective protections among the amino groups are therefore less frequent. Because of their stronger nucleophilicity,... 

Fluorination with DAST is a powerful tool in carbohydrate chemistry. The reaction usually proceeds in high yield with complete inversion. For fluorinations at a specific site to occur, other reactive groups are usually protected by standard protective groups. On the other hand, in several cases primary hydroxy groups in side chains can be substituted selectively by DAST without protection of ring hydroxy groups. Table 5 shows some recent examples of DAST lluorinations in carbohydrate chemistry, another example is the formation of the fluorinated kanamycin B derivative 15 for earlier work, see ref 38. 

O-Acyltyrosine derivatives bear the disadvantage of being active esters capable of acylating amino groups or other nucleophiles in a particularly efficient manner by intermolecular O—> N transfer (Scheme 9). Due to the reactivity of these phenyl esters, acyl groups such as acetyl or benzoyl, which are commonly used in carbohydrate chemistry, cannot be recommended for the protection of the tyrosine hydroxy group.f l... 

The electrochemical deprotection of carbonyl compounds proved to be a useful method especially in cases where alternative chemical reactions are unsuccessful, a-Keto- and a-hydroxythioacetals, when oxidized in MeCN-HoO (9 1 v/v) on a Pt anode, are transformed into the corresponding a-diones and a-ketols [142]. Diethyl dithioacetals of sugars were anodically oxidized in MeCN-H20 (5% H2O) on Pt electrode, and the substrates were successfully deprotected producing the correspondent carbohydrates in 65-85% yield [143]. It is noteworthy that protected hydroxy groups as esters or cyclic acetals were not affected. Selective deprotection to carbonyl compounds electrooxidizing mixtures of thioacetals, like a ketone and an aldehyde thioacetal, the former being preferentially deprotected, was described [144]. 

In all the above methods for oxidizing carbohydrates a stoichiometric oxidant is added to the reaction mixture. This can be avoided by using an electrochemical oxidation. A nickel hydroxide electrode has been applied for oxidizing isopropylidene-protected carbohydrates in aqueous base [26]. While secondary hydroxy groups fail to react under these conditions, the hemiacetal at the anomeric center is oxidized to the lactone in good yield [26]. 

A commonly used, protected carbohydrate containing a secondary hydroxy group is diiso-propylideneglucofuranose 23. Oxidation to the corresponding ketone 24 illustrates some of the most widely applied methods for oxidation of secondary alcohols (O Table 4). Again, the reactions can be divided into three main categories oxidations mediated by activated DMSO, oxidations with chromium(VI) oxides, and oxidations catalyzed by mthenium oxides. For oxidations with activated DMSO the Swern procedure is the most widely used [27]. 

Other partially protected carbohydrates also undergo very regioselective oxidation. Noteworthy is the oxidation of isopropylideneglucofuranose 29 to 5-ketofuranose 30 (O Scheme 10) [109]. For oxidation of the axial hydroxy group in cis-1,2 diols, the dibutylstannylene acetal method is often employed. Oxidation of methyl fucoside 31 with this procedure gives ketone 32 in good yield (O Scheme 10) [111]. 

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