Synthesis of (10Z)- and (10E)-19-Fluoro-1α, 25-dihydroxyvitamin D_3 : Compounds to Probe Vitamin D Conformation in Receptor Complex by ^<19>F-NMR

概要

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To study the interaction of vitamin D with its receptor by ^<19>F-NMR, (5Z, 10Z)-and (5Z, 10E)-19-fluoro-1α, 25-dihydroxyvitamin D_3 were synthesized starting from vitamin D_2 via electrophilic fluorination of vitamin D-SO_2 adducts as the key step. Regio- and stereoselective electrophilic fluorination at C(19) of vitamin D-SO_2 adducts was achieved under the conditions using (PhSO_2)_2NF and bulky bases. The stereochemistry of the addition and elimination of SO_2 of various vitamin D derivatives was studied in detail. SO_2 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 SO_2 from 19-substituted vitamin D-SO_2 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.
社団法人日本薬学会の論文
2000-10-01