Synthesis and biological characterization of 1 alpha,24,25-trihydroxy-2 beta-(3-hydroxypropoxy)vitamin D-3 (24-hydroxylated ED-71)

24-Hydroxylated derivatives were synthesized in 24(R) and 24(S) forms by th e convergent method as analogs related to 1 alpha ,25dihydroxy-2 beta-(3-hy droxypropoxy)vitamin D-3. In the convergent synthesis, the A-ring fragment, synthesized from diethyl D-tartarate, and the C/D-ring fragments in 24(R) and 24(S) forms (vitamin D numbering), obtained from vitamin D-2 via the In hoffen-Lythgoe diol, were coupled in moderate yields to give 1 alpha ,24(R) ,25-trihydroxy-2 beta-(3-hydroxypropoxy)vitamin D-2 and 1 alpha ,24(S).25-t rihydroxy-2 beta-(3-hydroxypropoxy)vitamin D-3. In preliminary biological e valuations, 24-hydroxylation of 1 alpha ,25-dihydroxy-2 beta-(3-hydroxyprop oxy)vitamin D-3 caused weakened affinity to vitamin D binding protein in vi tro and less calcemic activity in vivo compared to the parent compound. Whi le the affinity to vitamin D receptor in 24(R) epimer was sustained, the af finity in 24(S) epimer was less than that of the parent compound. (C) 2001 Elsevier Science Inc. All rights reserved.