Deoxy‐nitrosugars 12th communication Synthesis of isosteric mono‐phosphonate analogues of β‐and α‐<scp>D</scp>‐fructose 2,6‐bisphosphate

Abstract

Abstract A synthesis of the isosteric mono‐phosphonate analogues 2a and 19 of the β‐and α‐ D ‐fructose 2,6‐bisphosphate, respectively, is described. Chain elongation of the 1‐deoxy‐1‐nitro‐ D ‐arabinose 3 ( Scheme 1 ) by a Henry reaction with paraformaldehyde followed by protection of the resulting alcohol (methoxymethyl ether) and a radical‐chain substitution by nitromethane anion gave the key intermediates, the gluco ‐anhydroalditol 6 and the manno ‐anhydroalditol 7 . These products equilibrated under basic conditions. Conversion of 7 to the aldehyde 9 , Abramov reaction of 9 with diphenyl phosphite followed by deoxygenation according to Barton gave the phosphonate 11 ( Scheme 2 ). Selective hydrogenolysis of 11 , phosphorylation and deprotection gave 2 which was converted to the tetrasodium salt 2a . Similarly, 6 was transformed into the isosteric phosphonate analogue 19 of the α‐ D ‐fructose 2,6‐bisphosphate ( Scheme 3 ).