An Improved Degradation Procedure For Determination Of The Absolute Configuration In Chiral Isoquinoline And Beta-Carboline Derivatives

A reliable method for the determination of the absolute configuration of chiral isoquinolines, naphthylisoquinolines, michellamines and beta-carbolines is described. The ruthenium-mediated oxidative degradation of the di- or tetra-hydropyridine heterocycle in these structures provides simple amino acid derivatives, which can be analysed by GC after Mosher-type derivatization. The method allows for the secure determination of the absolute configuration at the stereocentres C-1 or C-3 in a single step. By using a mass-selective detector instead of a flame ionization detector for GC analysis of the amino acid derivatives, the procedure offers a more sensitive detection and unambiguous characterization of the degradation products. Because of this improved method, the required stereo-information is reliably available with as little as 0.5 mg of the analysate, even for complex natural products, such as the michellamines. The broad applicability of the procedure is demonstrated by a variety of examples taken mainly from the field of natural products chemistry. Copyright (C) 1996 Elsevier Science Ltd