New analogues of fosfomycin—synthesis of diethyl (1R,2R)- and (1S,2R)-1,2-epoxy-3-hydroxypropylphosphonates

The trans-configured fosfomycin analogue, diethyl (1R,2R)-1,2-epoxy-3-hydroxypropylphosphonate, was synthesised via the intramolecular Williamson reaction from 3-O-protected (trityl or TBDMS) or even unprotected diethyl (1S,2R)-2,3-dihydroxy-1-mesyloxypropylphosphonate, which was obtained from the known diethyl (1S,2R)-2,3-O-cyclohexylidene-1,2,3-trihydroxypropylphosphonate. On the other hand, the cis-analogue, diethyl (1S,2R)-1,2-epoxy-3-hydroxypropylphosphonate, could only be prepared from diethyl (1R,2R)-2-hydroxy-1-mesyloxy-3-trityloxypropylphoshonate.

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Diethyl (1S,2R)-1,2-epoxy-3-hydroxypropylphosphonateC7H15O5PEe = 100%[α]D20=-10.2 (c 1.0, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1S,2R)

Diethyl (1R,2R)-1,2-epoxy-3-hydroxypropylphosphonateC7H15O5PEe = 100%[α]D20=+24.8 (c 1.5, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,2R)

Diethyl (1S,2R)-1,2-epoxy-3-trityloxypropylphosphonateC26H29O5PEe = 100%[α]D20=-10.0 (c 1.15, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1S,2R)

Diethyl (1R,2R)-1,2-epoxy-3-trityloxypropylphosphonateC26H29O5PEe = 100%[α]D20=+17.8 (c 1.14, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,2R)

Diethyl (1S,2R)-3-(tert-butyldimethylsilyloxy)-1,2-epoxypropylphosphonateC13H29O5PSiEe = 100%[α]D20=+2.6 (c 1.3, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1S,2R)

Diethyl (1R,2R)-3-(tert-butyldimethylsilyloxy)-1,2-epoxypropylphosphonateC13H29O5PSiEe = 100%[α]D20=+16.0 (c 1.5, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,2R)

Diethyl (1R,2R)-2,3-dihydroxy-1-mesyloxypropylphosphonateC8H19O8PSEe = 100%[α]D20=-15.5 (c 1.25, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1R,2R)

Diethyl (1S,2R)-2,3-dihydroxy-1-mesyloxypropylphosphonateC8H19O8PSEe = 100%[α]D20=+20.15 (c 1.0, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (1S,2R)