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