Furan approach to vitamin D analogues. Synthesis of the A-ring of calcitriol and 1α-hydroxy-3-deoxyvitamin D3

Article abstract of DOI:10.1021/jo101155c

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.