Biocatalytic Asymmetric Construction of Secondary and Tertiary Fluorides from ß-Fluoro-α-Ketoacids.
Angew Chem Int Ed Engl
; 61(21): e202201602, 2022 05 16.
Article
de En
| MEDLINE
| ID: mdl-35165991
ABSTRACT
Fluorine is a critical element for the design of bioactive compounds, driving advances in selective and sustainable fluorination. However, stereogenic tertiary fluorides pose a synthetic challenge and are thus present in only a few approved drugs (fluticasone, solithromycin, and sofosbuvir). The aldol reaction of fluorinated donors provides an atom-economical approach to asymmetric C-F motifs via C-C bond formation. We report that the type II pyruvate aldolase HpcH and engineered variants perform addition of ß-fluoro-α-ketoacids (including fluoropyruvate, ß-fluoro-α-ketobutyrate, and ß-fluoro-α-ketovalerate) to diverse aldehydes. The reactivity of HpcH towards these fluoro-donors grants access to enantiopure secondary or tertiary fluorides. In addition to representing the first synthesis of tertiary fluorides via biocatalytic carboligation, the afforded products could improve the diversity of fluorinated building blocks and enable the synthesis of fluorinated drug analogs.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Fluorures
/
Fluor
Langue:
En
Journal:
Angew Chem Int Ed Engl
Année:
2022
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique