Synthesis and Biological Activity of Phosphonate Analogs of Mannose 6-Phosphate (M6P)

Two phosphonate analogs of mannose 6-phosphate (M6P) have been synthesized. The isosteric analog 1 was obtained by a Wittig–Horner reaction at position 6 of a sugar aldehyde. The non-isosteric analog 2 was obtained by a Michaelis–Arbuzov rearrangement of a 6-bromo derivative. In contrast to the non-isosteric analog 2, the isoster 1 was shown to bind to M6P receptors as effectively as does M6P itself, thus demonstrating the considerable potential of the system in drug design.