4-(pyridin-2-yl)thiazol-2-yl thioglycosides as bidentate ligands for oligosaccharide synthesis via temporary deactivation

Abstract

This study focusses on a new concept for oligosaccharide synthesis based on 4-(pyridin-2-yl)thiazol-2-yl thioglycosides that can either act as effective glycosyl donors or can be deactivated by stable bidentate complexation with palladium(II) bromide.

Fig. 1

Anomeric thiomoieties for bidentate ligation.

Fig. 2

X-Ray crystal structure of the acceptor complex 6. Projection view of the molecule with 50% thermal ellipsoids—the disordered component and solvent have been omitted for clarity. Selected crystallographic parameters for 6: Empirical formula C₃₈H₃₆Br₂N₂O₁₀PdS₂; formula weight 1011.03; monoclinic; space group C2, Z = 4. Unit cell dimensions: a = 26.134(2), b = 6.6651(5), c = 26.550(3) Å, β = 118.580(4)°, volume 4061.1(7) ų; number of reflections collected 41 064; independent reflections 7012 [R(int) = 0.064]; final R indices: R1 [I 4 2σ(I)] = 0.0431, wR2 (all data) = 0.0951. CCDC # 693543.

Scheme 1

Temporary deactivation concept.

Scheme 2

Synthesis/evaluation of SPT donor 4 and acceptor 6. Reagents and conditions: (i) Na/MeOH; (ii) MeCN; (iii) 1. MeONa/MeOH, 2. BnBr/NaH, DMF; (iv) 1. NaOMe/MeOH, 2. TrCl, C₅H₅N, 3. BzCl; (v) 1. PdBr₂, 3 Å MS, 1,2-DCE, 2. 10% TFA/wet DCM, 0 °C; (vi) 1. AgOTf, 3 Å MS, DCM, 2. NaCN, acetone.

Scheme 3

Synthesis of pneumococcal oligosaccharides.