Different O-glycosyl trichloroacetimidates bearing base sensitive Fmoc protected hydroxy groups were efficiently prepared with CCl(3)CN using a catalytic amount of sodium hydride. The resulting glycosyl donors were engaged in glycosylation reactions both in solution and on solid support with a new ester-type linker with good results. In both approaches, Fmoc groups were afterward quantitatively cleaved using mild basic conditions.

Oligosaccharides are known to be important molecules in various biological processes; therefore, they have gained increasing interest in recent years. [1] However, in contrast to oligopeptides [2] and oligonucleotides [3] which are routinely constructed on automated synthesizers employing standardized building blocks and polymer supports, no generally applied synthetic methodology has yet appeared for the solidphase synthesis of complex oligosaccharides. [4] Success in this challenging task would provide several advantages over solution-phase techniques: 1) the required standardized building blocks could become commercially available, 2) an excess of building blocks and/or reagents could be used to drive reactions to completion, 3) the synthesis could become much faster, and 4) purification procedures could become simpler.Another fundamental key issue for solid-phase oligosaccharide synthesis is the availability of a high-yielding and stereoselective glycosylation strategy. Of the various glycosyl donors employed for this purpose, [5±11] O-glycosyl trichloroacetimidates [12] are suitable because of their high glycosyldonor properties in the presence of just catalytic amounts of a (Lewis) acid. In combination with solvent and temperature effects, type of catalyst, protecting-group pattern, and anchimeric assistance these donors also permit the desired control of the stereoselectivity at the anomeric center. [13] An additional requirement for solid-phase oligosaccharide synthesis is access to branching which is found in many oligosaccharides and glycoconjugates but not in peptides and oligonucleotides. Thus, for chain extension and branching, besides permanently protected functional groups, to be liberated only after completion of the solid-phase oligosaccharide synthesis, a suitable temporary-protectinggroup pattern is required. This temporary-protecting-group pattern provides the orthogonality required for branching and should also accommodate the demands of the linker which necessitates an additional temporary functional group.Based on our recent studies on new temporary protecting groups, [12, 14] new linker types, [14] and the synthesis of branched oligosaccharides, [12e, 15] we report herein a novel strategy which COMMUNICATIONS 4489 were measured at low temperatures (4.2 K or 78 K). The source was kept at room temperature. Spectra were recorded over a velocity range of AE 25 mm s À1 using an NaI(Tl) scintillation counter. Fitting of the spectra was carried out on the basis of the theoretically expected lineshape arising from the allowed transitions between the quadrupolar-split energy levels of the ground state (I ¼ 5/2) and the excited state (I ¼ 7/2).[10] a) The compound crystallizes in the monoclinic space group P2 1 /c, a ¼ 11.743 (2). Lorentz, polarization, and absorption corrections; 17 068 reflections; range 1.74 q 27.53; 9436 unique data; 8164 with I ! 2s(I). Structure solution was performed with SHELXS-97 using direct methods. [10b] Refinement was done against F 2 using SHELXL-97. [10c] All ...

Success in discovering bioactive peptide mimetics is often limited by the difficulties in correctly transposing known binding elements of the active peptide onto a small and metabolically more stable scaffold while maintaining bioactivity. Here we describe a scanning approach using a library of pyranose-based peptidomimetics that is structurally diverse in a systematic manner, designed to cover all possible conformations of tripeptide motifs containing two aromatic groups and one positive charge. Structural diversity was achieved by efficient selection of various chemoforms, characterized by a choice of pyranose scaffold of defined chirality and substitution pattern. A systematic scanning library of 490 compounds was thus designed, produced, and screened in vitro for activity at the somatostatin (sst(1-5)) and melanin-concentrating hormone (MCH(1)) receptors. Bioactive compounds were found for each target, with specific chemoform preferences identified in each case, which can be used to guide follow-on drug discovery projects without the need for scaffold hopping.

Galactose and mannose building blocks 9 and 12 were designed for the solid phase synthesis of oligosaccharides (SPOS). Both compounds were employed after condensation with benzoic acid function containing resin 10 in SPOS of human milk trisaccharide 1 and oligomannosides 2-4 (a-(1®2)-linked hexamer). Thus, in this approach a special linker development was not required and with the temporary protective groups phenoxyacetyl (PA) and 9-fluorenylmethoxycarbonyl (Fmoc) as part of compounds 7-12 the strategy offers the additional advantage of having the anomeric centre at the reducing end available for further manipulations.

No abstract