Synthesis of (1 R ,2 R )‐ and (1 S ,2 R )‐1,2‐Epoxy‐3‐hydroxypropylphosphonates as Analogues of Fosfomycin

Cyclohexylammonium (1 R ,2 R )‐1,2‐epoxy‐3‐hydroxypropylphosphonate was conveniently synthesized from dibenzyl (1 S ,2 R )‐2,3‐ O ‐cyclohexylidene‐1,2,3‐trihydroxypropylphosphonate by a reaction sequence including mesylation, hydrolysis of acetal, intramolecular Williamson reaction, and hydrogenation in the presence of cyclohexylamine. For dibenzyl (1 S ,2 R )‐2,3‐ O ‐cyclohexylidene‐1,2,3‐trihydroxypropylphosphonates the same approach was not successful, since prior the epoxide‐ring closure tritylation of HO–C3 in dibenzyl (1 R ,2 R )‐2,3‐dihydroxy‐1‐mesyloxypropylphosphonate was necessary and the hydrogenolysis of dibenzyl (1 S ,2 R )‐1,2‐epoxy‐3‐trityloxypropylphosphonate yielded a complex reaction mixture.