Synthesis of (1R,2R)- and (1S,2R)-1,2-epoxy-3-hydroxypropylphosphonates as analogues of fosfomycin.
Cyclohexylammonium (1R,2R)-1,2-epoxy-3-hydroxypropylphosphonate was conveniently synthesized from dibenzyl (1S,2R)-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 (1S,2R)-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 (1R,2R)-2,3-dihydroxy-1-mesyloxypropylphosphonate was necessary and the hydrogenolysis of dibenzyl (1S,2R)-1,2-epoxy-3-trityloxypropylphosphonate yielded a complex reaction mixture.
Wróblewski
Andrzej E
AE
Bioorganic Chemistry Laboratory, Faculty of Pharmacy, Medical University of Lódz, Lódz, Poland. andrzej.wroblewski@umed.lodz.pl
Szewczyk
Eligia M
EM
Bak-Sypień
Irena I
II
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D005578:Fosfomycin / Q000031:analogs & derivatives*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D063065:Organophosphonates; D005578:Fosfomycin