Synthesis of 25-hydroxyvitamin D(3) and 26,26,26,27,27,27-hexadeutero-25-hydroxyvitamin D(3) on solid support.
A convenient five-step route to 25-hydroxylated vitamin D(3) compounds on (hydroxymethyl)polystyrene support is reported. A CD-side chain fragment was anchored to the solid phase through an ester group at C25 and coupled to an A ring building block to assemble the vitamin D triene system by the Wittig-Horner approach. Deprotection of the hydroxy group was carried out on the support, prior to functionalization at C25. The title compounds were released from the resin in excellent global yield by nucleophilic attack on the ester carbonyl group using commercially available organometallic reagents. This key last step offers an opportunity for the efficient generation of 26,27-labeled compounds and also for diversification at the side chain without need for a pool of side chain fragments.
Nicoletti
Daniel
D
Departamento de Química Orgánica y Unidade Asociada al CSIC, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.
Mouriño
Antonio
A
Torneiro
Mercedes
M
D002112:Calcifediol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry*; D002762:Cholecalciferol; D015394:Molecular Structure; D013237:Stereoisomerism
C544634:26,26,26,27,27,27-hexadeutero-25-hydroxyvitamin D(3); D002762:Cholecalciferol; D002112:Calcifediol