Synthesis of (10Z)- and (10E)-19-Fluoro-1α, 25-dihydroxyvitamin D₃ : Compounds to Probe Vitamin D Conformation in Receptor Complex by ¹⁹F-NMR

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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 form 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. Dyesensitized photochemical isomerization of 19-fluorovitamin D derivatives was studied in detail. The rapid isomer ization 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-Flurovitamin Ds were also interconverted thermally probably via the corresponding previtamin D by 1, 7-sigmatropic isomerization.