Convergent total synthesis of (+)-calcipotriol: A scalable, modular approach to vitamin D analogs.
Proc Natl Acad Sci U S A
; 119(18): e2200814119, 2022 05 03.
Article
em En
| MEDLINE
| ID: mdl-35476519
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 facile preparation of various C20-arylated derivatives that show promising biological activity in an initial bioassay.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Psoríase
/
Vitamina D
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article