Questioning the γ-gauche effect: stereoassignment of 1,3-disubstituted-tetrahydro-ß-carbolines using 1H-1H coupling constants.
Org Biomol Chem
; 17(27): 6687-6698, 2019 07 21.
Article
en En
| MEDLINE
| ID: mdl-31232413
ABSTRACT
The Pictet-Spengler reaction of tryptophan esters and aldehydes has been widely applied in natural product synthesis and medicinal chemistry. To date, the trans- or cis-configuration of 1,3-disubstituted tetrahydro-ß-carbolines (THßCs) formed in this reaction has most often been assigned based on the relative 13C chemical shifts of C1 and C3 in the diastereomers. Although the upfield shifts of C1 and C3 in trans-THßCs relative to cis-THßCs has been attributed to steric compression associated with the "γ-gauche" effect, we show that this effect is not borne out experimentally for other carbons that should suffer this same compression. Thus we developed a robust alternative method for stereochemical assignment based on 1H NMR coupling constants (31 examples) and supported by extensive DFT-based conformational analysis and calculation of 1H-1H coupling constants. DFT calculations of 13C NMR chemical shifts also cast doubt upon the role of the "γ-gauche" effect on C1 and C3 chemical shifts in trans-THßCs.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carbolinas
Idioma:
En
Revista:
Org Biomol Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos