Synthesis of a trisaccharide

Figure 8.7 HR-MAS spectra of resin-bound intermediates in the solid-phase synthesis of a trisaccharide using thiodonors. Traces a and b have been recorded using spin echo pulse sequences to suppress resonances of the resin. Traces c and d have been recorded using a standard proton experiment.

Scheme 10.9 Synthesis of a trisaccharide library on solid support using a two-directional glycosylation approach.

T. Sugawara and K. Igarashi, Synthesis of a trisaccharide component of the capsular polysaccharide of Streptococcus pneumoniae Type 19F, Carbohydr. Res. 772 195 (1988). 

The key reaction in oligosaccharide synthesis is the process in which a glycosyl donor and acceptor are coupled together under the agency of an appropriate promoter. In recent years, several novel and very effective glycosyl donors and promoters have been developed [2]. As a result, syntheses of oligosaccharides comprising five units are now considered to be routine, in contrast with 15 years ago when the synthesis of a trisaccharide was still a major task. 

Johnson AG (1964). Adjuvant action of bacterial endotoxins on the primary antibody response. Bacterial endotoxins Proc Symp Inst Microb Rutgers, State Uni Natl Sci Found. M. Landy and W. Braun. New Brunswick, NJ, Rutgers University Press 252-262. Johnstone KD, Dieckelmann M, Jennings MP, Toth I, Blanchfield JT (2005) Chemo-Enzy-matic Synthesis of a Trisaccharide-Linked Peptide Aimed at Improved Drug-Delivery. Curr Drug Deliv 2 215-222... 

A facile one-pot synthesis of a trisaccharide unit from the 51. common polysaccharide antigen of group B Streptococci using cyclohexane-1,2-diacetal (CDA) protected rhamnosides. Angew. 

F. W. Lichtenthaler and T. Metz, Efficient generation of /j-L-rhamnosidic linkages by the 2-ulosyl donor approach Synthesis of a trisaccharide with a central /j-L-rhamnose unit, Eur. J. Org. Chem.,... 

Scheme 8 Solid phase synthesis of a trisaccharide by the glycosyl sulfoxide method.

A rule of thumb in classical complex saccharide synthesis is that the addition of each monosaccharide unit requires on an average seven steps. Although there have been striking improvements in synthetic methods in recent years, the synthesis of a trisaccharide, for example, can still take 10 or more steps. The application of glycosidases to the synthesis of complex hetero-oligosaccharides represents a considerable saving in time and materials, and hence in overall cost. 

Kahne et al. [14] used a similar strategy in a very elegant synthesis of a trisaccharide in partically one step. The building blocks they used, the S-glycosides 13, 14, and 16, have considerably different reactivities at the anomeric center (Scheme 2). Phenylthiogly-coside 14 is definitely the least reactive. 

Scheme 6.20 Synthesis of a trisaccharide without using chromatographic purification...

This strategy was successfully applied fo a practical synthesis of a trisaccharide part of globotriaosyl ceramide. A highly fluorinated carboxyUc acid (Hfb) was also prepared and used for rapid and large-scale synthesis of a thyrotropin-releasing hormone (TRH). ... 

The photolysable 0-nitrobenzylidene acetal has-been used as an intermediate in the synthesis of a trisaccharide. Reaction of methyl et-D-mannopyranoside with i/-methoxystyrene and catalytic pyridinium tosj -late in DMSO gave a 7 3 mixture of the 4,6-0-acetals (13) and (U). 

SCHEME 10.6 Strategy for the solid-phase synthesis of a trisaccharide library using a phenylsulfonate traceless linker. 

Takahashi, T. et al.. Synthesis of a trisaccharide library by using a phenylsulfonate traceless linker on Synphase Crowns, Angew. Chem., Int. Ed. Engl, 40, 3230, 2001. 

The usefulness of dispiroketal to act as practical glycosyl donors was further illustrated in a facile one-pot synthesis of a trisaccharide fragment from the capsular polysaccharide of Group B Streptococci [80]. In the following example (Scheme 29), armed perbenzylated ethyl l-thio-oj-L-rhamnopyranoside donor 157 was treated with semidisarmed dispiroketal 158 under IDCP promoted glycosylation to provide disaccharide 159 in 59% yield. Glycosidation of acceptor 159 with acceptor 160 with the more potent NIS/TfOH couple afforded protected... 

Scheme 21. Phthalic acid-tethered synthesis of a trisaccharide.

The synthesis of a trisaccharide fragment of some orthosomycin antibiotics is referred to in Chapter 3. 

These syntheses established the automated synthesis as an efficient and rapid way of assembling oligosaccharides. Both trichloroacetimidates and phosphates were competent donors and acetate and levulinoate could be used as temporary protecting groups for the synthesis. These two approaches were combined for an automated synthesis of a trisaccharide on a 100 (xmol scale (Scheme 8). 

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