Convergent total synthesis of (+)-calcipotriol: A scalable, modular approach to vitamin D analogs.

ABSTRACT: A convergent approach for the total synthesis of calcipotriol (brand name: Dovonex), a proven vitamin D analog used for the treatment of psoriasis, and medicinally relevant synthetic analogs is described. A complete approach, not wedded to semisynthesis, toward both the A-ring and CD-ring is reported. From a retrosynthetic standpoint, hidden symmetry within the decorated A-ring is disclosed, which allowed for scalable quantities of this advanced intermediate. In addition, a radical retrosynthetic approach is described, which highlights an electrochemical reductive coupling as well as an intramolecular hydrogen atom transfer Giese addition to establish the 6,5-transcarbon skeleton found in the vitamin D family. Finally, a late-stage decarboxylative cross-coupling approach allowed for the fa

SUBMITTER: Gu J 

PROVIDER: S-EPMC9170165 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature