Synthesis of (10Z)- and (10E)-19-fluoro-1α,25-dihydroxyvitamin D3: Compounds to probe vitamin D conformation in receptor complex by 19F-NMR

Article abstract of DOI:10.1248/cpb.48.1484

To study the interaction of vitamin D with its receptor by ¹⁹F-NMR, (5Z,10Z)- and (5Z,10E)-19-fluoro-1α,25-dihydroxyvitamin D₃ were synthesized starting from vitamin D₂ via electrophilic fluorination of vitamin D-SO₂ adducts as the key step. Regio- and stereoselective electrophilic fluorination at C(19) of vitamin D-SO₂ adducts was achieved under the conditions using (PhSO₂)₂NF and bulky bases. The stereochemistry of the addition and elimination of SO₂ of various vitamin D derivatives was studied in detail. SO₂ causes Z-E isomerization of the 5,6-double bond of vitamin D and adds to the resulting (5E)-isomer from the sterically less hindered side opposite to the substituent at C(1). Elimination of SO₂ from 19-substituted vitamin D-SO₂ adducts proceeded exclusively in a suprafacial manner with respect to the diene part under either thermal or reductive conditions. Dye-sensitized photochemical isomerization of 19-fluorovitamin D derivatives was studied in detail. The rapid isomerization at the 5,6-double bond was followed by the slow isomerization at the 10,19-double bond to yield the (5E,10Z)-isomer (by nomenclature of the 1-OH derivatives) as the major product. (10Z)- and (10E)-19-Fluorovitamin Ds were also interconverted thermally probably via the corresponding previtamin D by 1,7-sigmatropic isomerization.

Full text of DOI:10.1248/cpb.48.1484

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