Asymmetric total synthesis of (+)-(2R,4'R,8'R)-α-tocopherol enabled by enzymatic desymmetrization.
Org Biomol Chem
; 20(14): 2909-2921, 2022 04 06.
Article
em En
| MEDLINE
| ID: mdl-35322842
ABSTRACT
A new and highly stereoselective synthesis of chiral diol (S)-14, the common synthetic intermediate to (+)-(2R,4'R,8'R)-α-tocopherol (1), was accomplished in seven steps with 13.8% overall yield. This developed route featured a lipase-catalyzed desymmetric hydrolysis of prochiral diester 39a, which was prepared through a challenging Heck coupling, to chiral quaternary carbon-containing monoester (R)-37a of the correct configuration in 81% yield and 96.7% ee, to the best of our knowledge, leading to the most efficient enzymatic desymmetric synthesis of the chiral chroman skeleton of vitamin E members reported to date. Coupled with the modified preparation of the phytol-derived side chain, the chemoenzymatic total synthesis of 1 was completed in 15 longest linear steps with 3.1% overall yield.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Vitamina E
/
Alfa-Tocoferol
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article