Conceptually new sulfone analogues of the hormone 1 alpha,25-dihydroxyvitamin D-3: Synthesis and preliminary biological evaluation

A conceptually new series of vitamin Ds-like nonfluorinated and fluorinated 16-ene side chain tert-butyl sulfones 3-7 has been synthesized. Even thoug h these novel C,D-ring side chain analogues of the hormone 1 alpha,25-dihyd roxyvitamin Ds (1, 1,25D(3)) lack a terminal OB group, thought previously t o be essential for high biological activity, they are highly antiproliferat ive and, in several cases, transcriptionally active in vitro but desirably noncalcemic in vivo. The side chain sulfone;group may be binding to the nVD R as a hydrogen-bond acceptor, in contrast to the hydrogen-bond donor funct ion of the 25-OH group of natural 1,25D(3).