Stereoselective synthesis of 1β,25-Dihydroxyvitamin D3 and its 26,27-hexadeuterated derivative

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 164; pp. 56 - 58
• Main Authors: Loureiro, Julian, Maestro, Miguel A., Mouriño, Antonio, Sigüeiro, Rita
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.11.2016
• Subjects: 1β,25-Dihydroxyvitamin D3; Deuterated analogs; Pd-catalyzed cascades; Synthesis; Vitamin D3 metabolites; Vitamin D3 metabolites; Deuterated analogs; 1β,25-Dihydroxyvitamin D3; Synthesis; Pd-catalyzed cascades
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2015.09.007

[Display omitted] •A convergent synthesis of 1β,25-dihydroxyvitamin D3 was achieved from (R)-carvone.•The construction of the triene moiety is based on a Pd-catalyzed cascade in aqueous conditions.•The convergent approach allows isotope labeling in the last steps of the synthesis.•The synthetic route allows the preparation of 1β,25-dihydroxyvitamin D3 for biological testing. A mild convergent synthesis of 1β,25-dihydroxyvitamin D3 (3a), a metabolite of vitamin D3, and its C26,27-hexadeuterated derivative (3b) are described. The A-ring and the CD-fragments are constructed from (R)-carvone and Inhoffen–Lythgoe diol, respectively. The triene system is assembled by a Pd(0)-catalyzed process, which involves an enol-triflate (A-ring fragment) and an alkenyl boronate (CD-side chain fragment). Deuterium labeling is introduced at the last step of the synthesis.