3-DEOXY-3-FLUOROPYRIDOXAMINE 5'-PHOSPHATE: SYNTHESIS AND CHEMICAL AND BIOLOGICAL PROPERTIES OF A COENZYME B6 ANALOG

The C-3 deoxygenation of CDP-6-deoxy-l-threo-d-glycero-4-hexulose is the key step in the biosynthesis of ascarylose which is a 3,6-dideoxy sugar found in the lipopolysaccharide of Yersinia pseudotuberculosis. This transformation, achieved by the catalysis of CDP-6-deoxy-l-threo-d-glycero-4-hexulose-3-dehydrase (E1) and CDP-6-deoxy-l-threo-d-glycero-4-hexulose-3-dehydrase reductase (E3), is initiated by a reversible dehydration followed by a stepwise electron transfer from NADH to reduce the resulting glucoseen−PMP adduct. An organic radical intermediate has been detected by EPR during E1−E3 catalysis, and its characteristics are consistent with a phenoxyl radical. Its formation has been hypothesized to involve a tautomerization of the glucoseen−PMP intermediate to a PMP−quinone methide species, which then serves as the electron acceptor during the reduction. In order to gain further experimental evidence supporting this proposed mechanism, the title compound (F-PMP) was synthesized and tested for its comp...