Alkylation glycoside synthesis

Biphasic systems have been effectively used in several enzyme-catalyzed reactions, including peptide and alkyl glycosides synthesis, esterification and transesterification, alcoholysis, hydrolysis, and enantiomeric resolution [2, 24, 60]. Although application of this particular bioconversion system has been used for final products, it is mostly used in the production of intermediate compounds, particularly optically active ones, that can be used as building blocks in the pharmaceutical and food sectors [61-64]. Updated reviews have addressed this matter [2, 4, 24, 60-63], and examples of some representative recent applications of this methodology are given in Table 8.1). 

Figure 8.7 Alkyl glycoside synthesis by a transglycosylation reaction catalysed byaglycosyl hydrolase (Enz). Hydrolysis is a competing side reaction.

The alcohols most frequently used for alkyl glycoside synthesis are primary straight-chain alcohols from methanol to 1-octanol and occasionally longer alcohols [67]. However, secondary alcohols have been used as weU, e.g. with almond /8-glucosidase [79]. More complex alcohols can also be used as substrates, but that is outside the scope of this review because the products are not used as surfactants. 

Scheme 8.7. Nucleoside synthesis, glycoside synthesis, and aromatic alkylation with a dielectrophilic donor.

The Fischer- Helferich method, as a direct anomeric-oxygen replacement reaction (Scheme 1, path A), has been very successfully applied for syntheses of simple alkyl glycosides. However, because of its reversibility, it has not gained general importance in the synthesis of complex oligosaccharides and glycoconjugates (1). 

Bessmertnykh A, Henin F, Serra-Muns A, Muzart J, Baillia H (2006) Synthesis of C-8 alkyl glycosides via palladium-catalyzed telomerization of butadiene with o-benzylated aldoses. CarbohydrRes 341 153-159... 

The direct allylation of radical precursors (e.g., alkyl hahdes, thioacyl derivatives) with allyltributylstannane in the presence of an initiator represents a well-established protocol for carbon-carbon bond formation [29,30]. This methodology provides a convenient means for introducing an allyl group to the anomeric carbon of carbohydrates [31]. hi their recent work on the preparation of building blocks for C-glycoside synthesis, Postema and coworkers... 

Further improvements in the synthesis of pyruvated saccharide building blocks are achieved when the l,l,3,3-tetraisopropyl-l,3-disiloxane-l,3-diyl group (TIPS) is used for the Noyori-acetalation. 4,6-TIPS-protected glycosides such as 9 are conveniently prepared from the corresponding alkyl glycosides 8 in two steps and can be converted into the respective pyruvated glycosides 10 under essentially thermodynamic conditions [35b] (Scheme 2). 

SCHEME 4.56 Regioselective glycoside synthesis by anomeric O-alkylation. 

Herscovici, J, Muleka, K, Boumaiza, L, Antonakis, K, C-glycoside synthesis via glycal alkylation by olefinic derivatives, J. Chem. Soc., Perkin Trans. 1, 1995-2009, 1990. 

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