CRYSTAL-STRUCTURE AND NMR ANALYSIS OF LACTULOSE TRIHYDRATE

The C-13 CPMAS n.m.r. spectrum of 4-O-beta-D-galactopyranosyl-D-fructose (lactulose) trihydrate, C12H22O11.3 H2O, identifies the isomer in the crystals as the beta-furanose. This is confirmed by a crystal structure analysis, using CuK-alpha X-ray data at room temperature. The space group is P2(1)2(1)2(1), with Z = 4 and cell dimensions a = 9.6251(3), b = 12.8096(3), c = 17.7563(4) angstrom. The structure was refined to R = 0.031 and R(w) 0.025 for 1929 observed structure amplitudes. All the hydrogen atoms were unambiguously located on difference syntheses. The conformation of the pyranose ring is the normal C-4(1) chair and that of the furanose ring is 4T3. The 1 --> 4 linkage torsion angles are O-5'-C-1'-O-1'-C-4 = -79.9(2)-degrees and C-1'-O-1'-C-4-C-5 = -170.3(2)-degrees. All hydroxyls, ring and glycosidic oxygens, and water molecules are involved in the hydrogen bonding, which consists of infinite chains linked together by water molecules to form a three-dimensional network. There is a three-centered intramolecular, interresidue hydrogen bond from O-3-H to O-5' and O-6'. The n.m.r. spectrum of the amorphous, dehydrated trihydrate suggests the occurrence of a solid-state reaction forming the same isomeric mixture as was observed in crystalline anhydrous lactulose, although the mutarotation of the trihydrate when dissolved in Me2SO is very slow.