jo101155c_si_001.pdf (1.6 MB)
0/0

Furan Approach to Vitamin D Analogues. Synthesis of the A-Ring of Calcitriol and 1α-Hydroxy-3-deoxyvitamin D3

Download (1.6 MB)
journal contribution
posted on 15.10.2010 by William H. Miles, Katelyn B. Connell, Gözde Ulas, Hannah H. Tuson, Elizabeth A. Dethoff, Varun Mehta, April J. Thrall
The A-rings of calcitriol (1α,25-dihydroxyvitamin D3) and 1α-hydroxy-3-deoxyvitamin D3 were synthesized using the furan approach. The critical steps in the synthesis of the A-ring of calcitriol involved an asymmetric carbonyl-ene reaction of 3-methylene-2,3-dihydrofuran with 3-(tert-butyldimethylsiloxy)propanal, a diastereoselective Friedel−Crafts hydroxyalkylation, an oxidation of the 2,3-disubstituted furan to give a γ-hydroxybutenolide, and a Peterson olefination. The A-ring (Z)-dienol of calcitriol was synthesized in 12 steps from 3-(tert-butyldimethylsiloxy)propanal in 17% yield.

History

Exports