Photoreaction Between Benzoylthiophenes and N-BOC-Tryptophan Methyl Ester

Authors

  • Julia Pérez-Prieto,

    Corresponding author
    1. Departamento de Química Orgánica/Instituto de Ciencia Molecular, Universidad de Valencia, Valencia, Spain
    • To whom correspondence should be addressed: Departamento de Quimica Organica/Instituto de Ciencia Molecular, Universidad de Valencia, Av. Vicent Andrks EstellCs s/n, 46100 Burjassot, Valencia, Spain. Fax: 34-963544939; e-mail: julia.perez@uv.es

      † To whom correspondence should be addressed: Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Camino de Vera s/n, 46071 Valencia, Spain. Fax: 34-963877809; e-mail: mmiranda@qim.upv.es

    Search for more papers by this author
  • Maria C. Morant-Miñana,

    1. Departamento de Química Orgánica/Instituto de Ciencia Molecular, Universidad de Valencia, Valencia, Spain
    Search for more papers by this author
  • Raquel E. Galian,

    1. Departamento de Química Orgánica/Instituto de Ciencia Molecular, Universidad de Valencia, Valencia, Spain
    Search for more papers by this author
  • Miguel A. Miranda

    Corresponding author
    1. Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Valencia, Spain
    • To whom correspondence should be addressed: Departamento de Quimica Organica/Instituto de Ciencia Molecular, Universidad de Valencia, Av. Vicent Andrks EstellCs s/n, 46100 Burjassot, Valencia, Spain. Fax: 34-963544939; e-mail: julia.perez@uv.es

      † To whom correspondence should be addressed: Departamento de Química/Instituto de Tecnología Química UPV-CSIC, Universidad Politécnica de Valencia, Camino de Vera s/n, 46071 Valencia, Spain. Fax: 34-963877809; e-mail: mmiranda@qim.upv.es

    Search for more papers by this author

  • This paper is part of a special issue dedicated to Professor J. C. (Tito) Scaiano on the occasion of his 60th birthday.

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.

Ancillary