Synthesis and X-ray crystal and solution structures of 2,5-anhydro-3,4- O-(1,2-ethanediyl)- d-mannitol: a locked 4T3 furanose conformer

2,5-Anhydro-3,4- O-(1,2-ethanedyl)- d-mannitol ( 1) was prepared from 2,5-anhydro- d-mannitol ( 2) in three steps. The fused ring system was introduced by a phase-transfer alkylation using 1,2-dibromoethane. Its conformation in solution was determined by NMR studies at 500 MHz. Variable-temperature studies showed no lineshape change from 25 to 80° in D 2O. The data indicate that the five-membered ring is locked by the trans-fused six-membered 1,4-dioxane ring into a twist 4 T 3 conformation. A single-crystal X-ray study was carried out. The crystals are orthorhombic, C222 1, a= 4.7252 (6), b = 14.0364 (12), c = 13.268 (2) Å, Z = 4, with R = 0.032 for 894 observations. The molecule lies upon a crystallographic two-fold axis, and thus five-membered ring exists in a perfect 4 T 3 conformation with a pseudorotation angle of 0° and amplitude of 47.2°, in agreement with the NMR results. We have shown earlier that, among twenty possible conformers, phosphofructokinase acts specifically on the 4 T 3 conformer of the β anomer of dfructose 6-phosphate.