The activated vitamin D3 derivative 26,27-F6-1alpha,25(OH)2D3 (2a), its three A-ring
diastereomers (2b, 2c, 2d), and 5,6-trans isomer (2e) were prepared. Two analogues
(2b, 2c) of these isomers were synthesized by a palladium catalyzed coupling reaction
using vinyl bromide 5 and enynes (6a, 6b), which were derived from readily commercially
available 2S-(+)-glycidyl p-toluenesulfonate 7, as a common starting material. Competitive
vitamin D receptor (VDR) binding affinities of these diastereomers of 2a were evaluated.
Interestingly, the stereochemical effects at C-1,3 of 2a were considerably more moderate
than those of 1alpha,25(OH)2D3 (1). In particular, isomerization at the 5,6-double
bond of 2a only slightly reduced VDR affinity, whereas 5,6-trans-1alpha,25(OH)2D3
had a significantly lower binding affinity than 1.