Carbohydrates solid phase synthesis

Acetal handle 78 synthesized from Merrifield resin and 4-hydroxy-benzaldehyde was applied to the solid-phase synthesis of carbohydrates and 1-oxacephams (Scheme 41) [90]. For the latter, a 1,3-diol was initially anchored to the support to form a cyclic acetal. A ring opening reaction with DIBAL generated a resin-bound alcohol which was converted to the corresponding triflate for A-alkylation with 4-vinyl-oxyazetidin-2-one. A Lewis acid catalyzed ring closure released 1-oxa-cephams from the support. 

Urge, L., Otvos Jr., L., Lang, E., Wroblewski, K., Laczko, I., and Hollosi, M. (1992) Fmoc-protected, glycosylated asparagines potentially useful as reagents in the solid-phase synthesis of N-glycopeptides. Carbohydr. Res. 235, 83-93. 

Scheme 5.2 (a) Monosaccharide building blocks 1-3 selected for solid phase synthesis of heptasaccharide 16 (b) attachment of the first carbohydrate onto phenolic polystyrene through a new photocleavable o-nitrobenzyl-type linker29 (Bn = benzyl, Bz = benzoyl, Fmoc = 9-fluoromethyloxycarbonyl, Ph = phenyl, py = pyridine, TBDPS =t-butyldiphenylsilyl). 

Scheme 13.21 Solid-phase synthesis of carbohydrate bound glycopeptides.

Reduction is used for carbonyl functionalities [71, 230] such as thioesters [231], amides [232], and carbamates [233], as well as for sulfur [234] and selenium [122] compounds. Recently, the synthesis of a potential carbohydrate vaccine is described via an reduction-oxidation sequence [235]. An efficient solid-phase synthesis of pyrimidine derivatives that involved reduction of the corresponding nitro derivatives was developed by Makara et al. in 2001 (Scheme 3.9) [236]. 

J. Rademann and R. R. Schmidt, Solid-phase synthesis of a glycosylated hexapeptide of human sialophorin, using the trichloroacetimidate method, Carbohydr. Res. 269 217 (1995). 

Allyl carbonates can be cleaved by nucleophiles under palladium(O) catalysis. Allyl carbonates have been proposed for side-chain protection of serine and threonine, and their stability under conditions of /VT moc or /V-Boc deprotection has been demonstrated [107]. Prolonged treatment with nucleophiles (e.g., 20% piperidine in DMF, 24 h) can, however, lead to deprotection of Alloc-protected phenols [108,109]. Carbohydrates [110], tyrosine derivatives [107], and other phenols have been protected as allyl ethers, and deprotection could be achieved by palladium-mediated allylic substitution (Entry 9, Table 7.8). 9-Fluorenyl carbonates have been used as protected intermediates for the solid-phase synthesis of oligosaccharides [111]. Deprotection was achieved by treatment with NEt3/DCM (8 2) at room temperature. 

Other known oligonucleotide analogs include oligomers in which the heterocyclic bases have been modified [155] or replaced by other types of compound [156], Solid-phase syntheses of hybrids of DNA with peptides [157-163], with carbohydrates [164,165], and with PNA (peptide nucleic acids, see Section 16.4.1.2 [166-168]) have also been reported, and several strategies have been developed that enable the preparation of oligonucleotides with a modified 5 - or 3 -terminus [169-174] or of cyclic oligonucleotides [122,175], Various techniques for the parallel solid-phase synthesis of oligonucleotides have been developed for the preparation of compound libraries [176-181],... 

In early attempts directed towards the solid-phase synthesis of oligosaccharides, glycosidic bonds were formed by treating pyranosyl bromides with partially protected carbohydrates (Figure 16.16). These syntheses could be performed with either the pyranosyl bromide (glycosyl donor) [184,185] or the alcohol (glycosyl acceptor) [186— 188] linked to the support. 

The coupling protocols described in the two previous examples can be combined to allow for the synthesis of branched carbohydrates.19 The automated solid-phase synthesis of a tetrasaccharide is illustrated in Scheme 4. Both glycosyl phosphate and glycosyl imidate building blocks were used along with acetate and levulinate esters as temporary protecting groups. 

Oligolysine dendrimers with terminal carbohydrate structures were functionalised by solid-phase synthesis for well-defined construction of glycoclusters . Synthesis proceeded via coupling of lysine molecules. Eight amino groups are attached by peptide bonding to the periphery via a spacer-functionalised sialic acid derivative (Fig. 8.8). 

Many strategies have been and are still being developed to access oligosaccharides by chemical synthesis. This chapter focuses on recent developments in the automated solid-phase synthesis of oligosaccharides and emphasizes the recent advances of novel microreactor techniques for carbohydrate synthesis. 

Elofsson M, Roy S, Walse B, Kihlberg J, Solid-phase synthesis and conformational studies of glycosylated derivatives of helper-T-cell immunogenic peptides from hen-egg lysozyme., Carbohydr. Res., 17, 246 89-103, 1993. 

Nicolaou KC, Mitchell HJ, Flyaktakidou KC, Suzuki H, Rodriguez RM, 1,2-Seleno migrations in carbohydrate chemistry Solution and solid-phase synthesis of 2-deoxy glycosides, orthoesters, and allyl orthoesters, Angew. Chem. Int. Ed., 39 1089-1093, 2000. 

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