Syntheses and biological evaluation of novel 2α-substituted 1α,25-dihydroxyvitamin D3 analogues

Novel 2α-substituted 1α,25-dihydroxyvitamin D3 analogues were efficiently synthesized and their biological activities were evaluated. 2α-Methyl-1α,25-dihydroxyvitamin D3 (2), whose unique biological activities were previously reported, was modified to 2α-alkyl (ethyl and propyl) and 2α-hydroxyalkyl (hydroxymethyl, hydroxyethyl, and hydroxypropyl) analogues 3–7 by elongation of the alkyl chain and/or introduction of a terminal hydroxyl group. 2α-Hydroxypropyl-1α,25-dihydroxyvitamin D3 (7) exhibited an exceptionally potent calcium-regulating effect and a unique activity profile.