Junichi Oshida

The stereochemical configuration of the natural 1α,25-dihydroxyvitamin D3-26,23-lactone

Abstract Four possible diastereoisomers of 1α,25-dihydroxyvitamin D3-26,23-lactone were chemically synthesized and compared with the natural metabolite by high-pressure liquid chromatography. The four synthetic diastereoisomers of 1α,25-dihydroxyvitamin D3-26,23-lactone could be separated into three peaks by high-pressure liquid chromatography. The naturally occurring 1α,25-dihydroxyvitamin D3-26,23-lactone isolated from dog serum and in vitro incubation of chick kidney homogenates comigrated with 23(S)25(R)-1α,25-dihydroxyvitamin D3-26,23-lactone. The four diastereoisomers of 1α,25-dihydroxyvitamin D3-26,23-lactone were tested against naturally occurring 1α,25-dihydroxyvitamin D3-26,23-lactone to determine their relative competition in the 1α,25-dihydroxyvitamin D3-specific cytosol receptor binding assay for 1α,25-dihydroxyvitamin D3. 23(S)25(S)-1α,25-Dihydroxyvitamin D3-26,23-lactone was the best competitor followed by 23(R)25(R)-1α,25-dihydroxyvitamin D3-26,23-lactone and 23(R)25(S)-1α,25-dihydroxyvitamin D3-26,23-lactone, and 23(S)25(R)-1α,25-dihydroxyvitamin D3-26,23-lactone was the poorest competitor. Natural 1α,25-dihydroxyvitamin D3-26,23-lactone isolated from dog serum had almost the same binding affinity as that of 23(S)25(R)-1α,25-dihydroxyvitamin D3-26,23-lactone. These data unequivocally demonstrate that the stereochemistry of the natural 1α,25-dihydroxyvitamin D3-26,23-lactone has the 23(S) and 25(R) configuration.