Reversal of absolute stereochemistry of the pyrrolo[2,1-b]quinazoline alkaloids vasicine, vasicinone, vasicinol and vasicinolone

Abstract

The previously assigned 3R configuration of (-)-vasicinone has been reversed and this pyrrolo[2,1-b]quinazoline-9-one has been shown to have the 3S-configuration (3) on the basis of an X-ray diffraction study of (+)-vasicinone hydrobromide. Likewise, the 3R stereochemistry assigned earlier to (-)-vasicine (peganine) (1) on the basis of an X-ray analysis of its hydrochloride has also been reversed by reinvestigation of the X-ray diffraction analysis of the hydrobromide. The absolute stereochemistry of the alkaloids (+)-vasicinol (2) and vasicinolone (5) which have been inter-related, should also have the 3S-configuration. A study of the ¹H nmr spectroscopy of (-)-vasicine by the use of Mosher's method using MTPA [α-methoxy-α-(trifluoromethyl)phenylacetic acid] esters indicated an exception to this model for establishing the absolute configuration.