66760-28-9Relevant articles and documents
Studies on the A-Ring Diastereomers of 1α,25-Dihydroxyvitamin D3
Muralidharan, K. Raman,Lera, Angel R. de,Isaeff, Shawn D.,Norman, Anthony W.,Okamura, William H.
, p. 1895 - 1899 (1993)
The three A-ring diastereomers 3b (compound HL), 4a (compound HJ), and 4b (compound HH), of the steroid hormone 1α,25-dihydroxyvitamin D3 (1α,25-(OH)2-D3, 3a, compound C) have been synthesized and biologically evaluated. (R)-Carvone was converted in seven steps to the enantiomerically pure A-ring enyne 7a.Palladium-catalyzed cross-coupling of the latter with the CD-ring triflate 8 resulted in silyloxy dienyne 10, which was converted in three steps to 1β,25-(OH)2-3-epi-D3 (4b).Oxidation of the latter with Dess-Martin reagent afforded trienone 6c, which upon reduction with sodium borohydride followed by thermolysis generated the 1α-epimer 4a.An identical sequence converted 1α,25-(OH)2-D3 to its 1β-epimer 3b via trienone 5c.Reduction of the latter with sodium triacetoxyborohydride followed by thermal isomerization regenerated the hormone 3a.Relative competitive indices (RCIs) of these analogues, which reflect their ability to bind to the chick intestinal nuclear receptor under in vitro conditions, were determined.Analogues 3b, 4a, and 4b had RCI values of 0.8 +/- 0.1 percent, 24.0 +/- 4.5 percent, and 0.22 +/- 0.01 percent, respectively, in comparison to 1α,25-(OH)2-D3 whose value is 100 percent by definiton.In addition, in vivo biological evaluation of these analogues was performed to determine their ability to induce intestinal calcium absorption (ICA) and bone calcium mobilization (BCM) in vitamin D deficient chicks.Analogue 4a was effective in stimulating ICA and BCM whereas analogues 3b and 4b exhibited little potency in eliciting these biological effects.
