Synthesis of (10Z)- and (10E)-19-fluoro-1alpha,25-dihydroxyvitamin D3: compounds to probe vitamin D conformation in receptor complex by 19F-NMR.
To study the interaction of vitamin D with its receptor by 19F-NMR, (5Z,10Z)- and (5Z,10E)-19-fluoro-1alpha,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.
Shimizu
M
M
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Japan. shimizu@i-mde.tmd.ac.jp
Iwasaki
Y
Y
Ohno
A
A
Yamada
S
S
D005461:Fluorine; D009682:Magnetic Resonance Spectroscopy; D015335:Molecular Probes; D015394:Molecular Structure; D018167:Receptors, Calcitriol / Q000737:chemistry* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D014807:Vitamin D / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism
C419448:19-fluoro-1,25-dihydroxyvitamin D3; D015335:Molecular Probes; D018167:Receptors, Calcitriol; D014807:Vitamin D; D005461:Fluorine