STUDY OF THE PICTET-SPENGLER REACTION IN APROTIC MEDIA - SYNTHESIS OF THE BETA-GALACTOSIDASE INHIBITOR, PYRIDINDOLOL

Factors which influence the Pictet-Spengler reaction in nonacidic, aprotic media have been studied. The condensation has been shown to work well with aldehydes when tryptophan methyl ester derivatives and Nb-benzyltryptamines were employed as substrates. The optimum conditions were realized when the AT-benzyl derivatives were stirred with aldehydes in refluxing toluene. The factors (electrophilic character of the intermediate imine) which determine the ease of cyclization have been examined, as well as the effect of temperature on the condensation. The synthesis of many tetrahydro-J-carbolines, 6a-6i, 7a, and 7b, heretofore difficult to prepare, have been accomplished in good yield in the aprotic medium. This methodology has permitted the synthesis of the antibiotic pyridindolol 16. © 1979, American Chemical Society. All rights reserved.