Regioselective Acylation of Carbohydrates

To catalyze a protective step in a chemo-enzymatic synthesis of sugar derivatives or of more complex oligosaccharides. 

For instance, subtilisin-catalyzed esterification of lactosides has been used for a chemo-enzymatic approach to 6 -deoxy-6 -fluoro- and 6-deoxy-6-fluoro-lactosides 

Finally, Kren and coworkers have proposed the use of selectively acylated glycosides to be used as acceptors in a bi-enzymatic approach to the synthesis of di- and trisaccharides exploiting lipases/proteases and glycosidases (for instance, 6-0-acetyl-N-acetyl-D-glucosamine, 14, to give the corresponding chitobiose derivative 15) [44]. 

For the large-scale production of new bio-surfactants [45] and, more recently, of sugar-containing self-assembled organogels with nanostructured morphologies [46]. 

The latter materials were based on diesters of trehalose (16a), a symmetrical disaccharide with an a-1,1 glycosidic bond (16), synthesized by Candida antarctica lipase suspended in acetone. 

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This strategy using rapid automated synthesis of libraries of peptides and fluorescent screening of reactivity has allowed Miller to identify specific peptide-catalysts for specific applications such as the KR of an intermediate en route to an aziridomi-tosane [165,169], the KR of certain fert-alcohols [166], the regioselective acylation of carbohydrates [168], and finally the KR of AT-acylated fert-amino alcohols with s values from 19 to >50 (Scheme 21) [166],... 

Ueda Y, Muramatsu W, Mishiro K, Furuta T, Kawabata T (2009) Functional group tolerance in organocatalytic regioselective acylation of carbohydrates. J Org Chem 74 8802... 

Lee D, Taylor MS (2011) Borinic acid-catalyzed regioselective acylation of carbohydrate... 

Unfortunately, as none of these catalysts induced useful levels of selectivity in the KR of secondary aryl alkyl alcohols. Miller et al. set out to identify specific peptide-catalysts for specific applications using automated peptide synthesis and high-throughput fluorescent screening. This allowed them to unveil some particularly effective catalysts for various transformations such as the KR of an intermediate in the synthesis of aziridomitosane [22h, k], the KR of a series of tertiary alcohols [22i], the regioselective acylation of carbohydrates [22k], and the KR of N-acylated tert-amino alcohols [22ij. 

One particular feature of ionic liquids lies in their solvation properties, not only for hydrophobic compounds but also for hydrophilic compounds such as carbohydrates. Park and Kazlauskas reported the regioselective acylation of glucose in 99 % yield and with 93 % selectivity in [MOEMIM][BF4] (MOE = CH3OCH2CH2), values much higher than those obtained in the organic solvents commonly used for this purpose (Entry 18) [22] (Scheme 8.3-4). 

An extension of this tin chemistry to the regioselective acylation of unprotected sugars bound to a resin shows the possibility of using solid-phase techniques for the preparation of 0-acyl derivatives of carbohydrates [231]. Very recently, it has been reported that organotin-mediated multiple carbohydrate esterifications can be controlled by the acylating reagent and the solvent polarity. When acetyl chloride is used, the reactions are under thermodynamic control, whereas when acetic anhydride is employed, kinetic control takes place (O Scheme 31) [232]. 

Regioselective acylations of polyhydroxylated compounds such as carbohydrates, glycerols, steroids, or alkaloids have been carried out with lipases, esterases, and proteases [13, 20]. One example is the Candida antartica lipase (immobilized on acrylic resin) catalyzed monoacylation of the signalling steroid ectysone (1) giving selectively the 2-C)-acetate 2 (eq. (1)). Using vinyl acetate for this transesterification the reaction was irreversibly pushed to the product side, since the liberated enol instantaneously isomerizes to acetaldehyde [21]. The sometimes unfavorable aldehyde is avoided when 1-ethoxyvinyl acetates [22], trichloro- or -fluoroethyl esters [23 a, b], oxime esters [23 c] or thioesters [23 d] are employed for the quasi-irreversible reaction courses. 

The directed protection of nucleoside functional groups is a fundamental problem in nucleoside and nucleotide chemistry. Although several chemical methods are available for the regioselective acylation of the nucleoside carbohydrates, enzymatic... 

Eby R, Webster KT, Schuerch C (1984) Regioselective alkylation and acylation of carbohydrates engaged in metal complexes. Carbohydr Res 129 111... 

By taking advantage of the remarkable abihty of subtihsia [9014-01-1] to remain catalyticahy active ia anhydrous dimethylformamide, a number of carbohydrates and other sugar-related compounds have been regioselectively acylated with trichloroethyl butyrate (100). In the case of maltose [69-79-4] (76) and sahcia [138-52-3] (77), for example, acylation occurs exclusively at the C-6 positions. 

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