Furan approach to vitamin D analogues. Synthesis of the A-ring of calcitriol and 1α-hydroxy-3-deoxyvitamin D(3).
The A-rings of calcitriol (1α,25-dihydroxyvitamin D(3)) and 1α-hydroxy-3-deoxyvitamin D(3) 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.
Miles
William H
WH
Department of Chemistry, Lafayette College, Easton, Pennsylvania 18042, USA. milesw@lafayette.edu
Connell
Katelyn B
KB
Ulas
Gözde
G
Tuson
Hannah H
HH
Dethoff
Elizabeth A
EA
Mehta
Varun
V
Thrall
April J
AJ
D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D005663:Furans / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
C555278:1alpha-hydroxy-3-deoxyvitamin D3; D005663:Furans; D002117:Calcitriol; C039281:furan