Functionalized cyclodextrins: Synthesis and structural characterization of 6-deoxy-6-{4-[N-tert-butoxycarbonyl-2-aminoethyl]-imidazolyl}-cyclomaltoheptaose

Abstract

The synthesis and the structural characterization by X-ray diffraction analysis of a monofunctionalized β-cyclodextrin (β-CD), the 6-deoxy-6-{4-[N-tert-butoxycarbonyl-2-aminoethyl]-imidazolyl}-cyclomaltoheptaose, are reported. It crystallizes in the orthorhom-bic space group P2₁2₁2₁, with a = 17.250(9)Å, b = 19.45(1)Å, c = 23.24(1)Å, d_calc = 1.304 g/cm³ and Z = 4. The structure was refined to final indices R1 = 0.083 and wR2 = 0.24 (based on F_o ²) for the 4843 observed reflection with I ≤ 2σ(I). At the end of the refinement the presence of 12 water molecules per β-CD molecule distributed over 16 sites was detected. In the solid state the monofunctionalized β-CD molecule shows a ‘sleeping swan’-like shape with the covalently bonded Boc-amino-ethyl-imidazolyl moiety forming a folded structure with its terminal part inserted inside the hydrophobic cavity of the β-CD ring. The β-CD macrocycle presents only small differences with respect to the conformation observed in hydrated uncomplexed or methylated β-CDs. The macrocycle structure maintains an approximate seven-fold symmetry. The substituted β-CD molecules pack in layers parallel to the bc plane. The layers are stacked in an head-to-tail arrangement of the monomeric units, with formation of columns of molecules along the a axis. The layers are connected to each other by H-bonds through water molecules. Channels generated in the crystal by the packing of the macrocycles are filled with water molecules.

Key Words:

• β-Cyclodextrins
• monofunctionalized cyclodextrins
• synthesis
• solid state structure
• conformation