Quantum chemical CD calculations of dioncophylline A in the solid state

Abstract Although dioncophylline A ( 1 ) is the certainly best-investigated naphthylisoquinoline alkaloid, it still represents a challenging case for theoretical stereochemical investigations. Its biaryl axis, although being configurationally stable, still has a certain degree of rotational flexibility, rapidly twisting within certain margins, and thus, exerting a dramatic influence on the CD behavior of 1 . Therefore, solid-state CD spectroscopy might provide a unique chance to study this flexible compound in a conformationally ‘frozen’ form, as fixed in the crystal. Based on the X-ray derived coordinates of the single conformer found in the crystalline state, CD calculations were performed by three different approaches, viz. by CNDO/S-CI, TD-B3LYP, and DFT/MRCI, each permitting the unambiguous attribution of the absolute axial configuration of dioncophylline A ( 1 ) as P , which is in full agreement with the previous assignments. Furthermore, to examine a possible influence of the neighboring molecules in the crystal on the CD behavior of 1 , a set of dyads, each consisting of a given ‘central’ molecule and a second one from the nearest neighborhood, were considered at a semiempirical level, as well as a ‘one-piece’ cluster of 16 molecules from the crystal. The results were compared with those obtained by solution and solid-state CD spectroscopy, which confirmed the configurational assignment.