Syntheses and biological evaluation of novel 2 alpha-substituted 1 alpha,25-dihydroxyvitamin D-3 analogues

Novel 2 alpha-substituted 1 alpha,25-dihydroxyvitamin D-3 analogues were ef ficiently synthesized and their biological activities were evaluated. 2 alp ha-Methyl-1 alpha,25-dihydroxyvitamin D-3 (2), whose unique biological acti vities were previously reported, was modified to 2 alpha-alkyl (ethyl and p ropyl) and 2 alpha-hydroxyalkyl (hydroxymethyl, hydroxyethyl, and hydroxypr opyl) analogues 3-7 by elongation of the alkyl chain and/or introduction of a terminal hydroxyl group. 2 alpha-Hydroxypropyl-1 alpha,25-dihydroxyvitam in D-3 (7) exhibited an exceptionally potent calcium-regulating effect and a unique activity profile. (C) 2000 Elsevier Science Ltd. All rights reserv ed.