(10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3: an improved synthesis via 19-nor-10-oxo-vitamin D.
An efficient synthetic route to (10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3 was developed. The key feature of this pathway is the introduction of a 19-fluoromethylene group to a (5E)-19-nor-10-oxo-vitamin D derivative. The 10-oxo-compound was obtained via a 1,3-dipolar cycloaddition reaction of (5E)-1alpha,25-dihydroxyvitamin D with in situ generated nitrile oxide followed by ring cleavage of the formed isoxazoline moiety with molybdenum hexacarbonyl. Conversion of the keto group of (5E)-19-nor-10-oxo-vitamin D to the E and Z fluoromethylene group was achieved through a two-step sequence involving a reaction of lithiofluoromethyl phenyl sulfone followed by the reductive desulfonylation of the alpha-fluoro-beta-hydroxy sulfone. The dye-sensitized photoisomerization of the (5E)-19-fluorovitamin D afforded the desired (5Z)-19-fluorovitamin D derivatives, (10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3.
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Japan. shimizu@i-mde.tmd.ac.jp
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Shimizu
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Ohno
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Yamada
D002112:Calcifediol / Q000031:analogs & derivatives / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D005456:Fluorescent Dyes / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D014807:Vitamin D / Q000031:analogs & derivatives / Q000138:chemical synthesis*
C419448:19-fluoro-1,25-dihydroxyvitamin D3; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D008024:Ligands; D014807:Vitamin D; C039030:19-nor-10-keto-25-hydroxyvitamin D3; D002112:Calcifediol