Photoreaction between benzoylthiophenes and N-BOC-tryptophan methyl ester

Photochem Photobiol. 2006 Jan-Feb;82(1):231-6. doi: 10.1562/2005-03-15-RA-461.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Free Radicals
  • Models, Molecular
  • Photochemistry
  • Stereoisomerism
  • Thiophenes / chemistry*
  • Tryptophan / analogs & derivatives*
  • Tryptophan / chemistry

Substances

  • Free Radicals
  • N-BOC-Trp methyl ester
  • Thiophenes
  • Tryptophan