Synthesis of 1-[13CD3]-9-cis-retinoic acid

Article abstract of DOI:10.1002/jlcr.2580360807

1-[¹³CD₃]-9-cis-Retinoic acid was prepared in 8 steps from 2,6-dimethylcyclohexanone. Alkylation of 2,6-dimethylcyclohexanone under LiHMDS/MnBr₂/¹³CD₃I gave the corresponding labeled 2-[¹³CD₃]-2,2,6-trimethylcyclohexanone 4 in good yield. Further functionalization of 4 to 6-[¹³CD₃]-β-cyclocitral 6 proceeded through a Shapiro reaction. Aldehyde 6 was condensed with ethyl 3,3-dimethylacrylate to afford the corresponding bicyclic pyranone 7. Reduction of 7 to lactol 8, followed by acid-catalyzed ring opening gave the 9-cis-aldehyde 9. Wittig-Horner olefination and saponification afforded the title compound in good overall yield and in excellent isotopic purity.