Biologically Relevant Phosphoranes: Structural Characterization of Glucofuranose- and Xylofuranose-Based Phosphoranes

Carbohydrate-based phosphoranes were synthesized by reacting 2,2'-ethylidenebis(4,6-di-tert-butylphenyl)-fluorophosphite with 1,2-O-isopropylidene-a-D-glucofuranose, β-chloralose, and 1,2-isopropylidene-a-D-xylofuranose to form the monocyclic biophosphoranes 1-3, respectively, in the presence of N-chlorodiisopropylamine. Synthesis of the monocyclic biophosphorane 4 was achieved by reacting tris(2,6-di-isopropylphenyl)phosphite with 1,2-O-isopropylidene-a-D-glucofuranose in the presence of N-chlorodiisopropylamine. X-ray analysis of 1-4 revealed trigonal bipyramidal structures with the carbohydrate components occupying axial-equatorial sites. An eight-membered ring in 1-3 occupied diequatorial sites of the trigonal bipyramid. Solution and solid state 31 P and solution 19 F, 1 H, and 13 C NMR measurements including variable temperature and correlation spectroscopy studies established retention of the solid state structure in solution. A dynamic equilibrium exists among two isomeric forms. These biophosphoranes serve as models for active sites of phosphoryl transfer enzymes. The rapid exchange process reorients the carbohydrate component of the trigonal bipyramidal phosphorane. At an active site, this type of pseudorotational behavior provides a mechanism that could bring another active site residue into play and account for a means by which some phosphoryl transfer enzymes express promiscuous behavior.