Photoreaction between benzoylthiophenes and N-BOC-tryptophan methyl ester.
Drug-induced photoallergy requires as the first step formation of covalent drug-protein photoadducts. One of the key amino acids involved in this process is tryptophan (Trp). In this context, several diaryl ketones, including 2-benzoylthiophene (BT), [2-(5-benzoyl-5-thienyl)]-2-methylpropanoic methyl ester (TPA methyl ester) and 4-(2-thienylcarbonyl)phenyl]-2-methylpropanoic methyl ester (SUP methyl ester) have been irradiated in the presence of N-BOC-(L)-tryptophan methyl ester. Laser flash photolysis has allowed to detect three neutral radicals (ketyl, indolyl and skatolyl radicals) resulting from formal hydrogen-atom abstraction. This correlates well with the isolation of homodimers, as well as with cross-coupling products, in the preparative irradiation. The main cross-coupling products were in all cases lactones arising from the reaction of the Trp-derived skatolyl radicals with the corresponding ketyl radicals. These lactones were obtained as the (4R) stereoisomers with remarkable diasteroselectivity. No coupling products through the phenyl p-position of BT or TPA methyl ester were found. By contrast, ketone homodimers and cross-coupling products arising from reaction through the thienyl 5-position were obtained when using BT and SUP methyl ester; this is very interesting, because stable LAT-derived products are difficult to isolate.
Pérez-Prieto
Julia
J
Departamento de Química Orgánica/Instituto de Ciencia Molecular, Universidad de Valencia, Valencia, Spain. julia.perez@uv.es
Morant-Miñana
Maria C
MC
Galian
Raquel E
RE
Miranda
Miguel A
MA
D005609:Free Radicals; D008958:Models, Molecular; D010777:Photochemistry; D013237:Stereoisomerism; D013876:Thiophenes / Q000737:chemistry*; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000737:chemistry
D005609:Free Radicals; C510897:N-BOC-Trp methyl ester; D013876:Thiophenes; D014364:Tryptophan