Cmr Assignments of the Securinine Alkaloids

Abstract

The cmr spectrum of securinine (11, allosecurinine (2), and their boro- hydride reduction products (3 and 4) have been assigned on the basis of lanthanide shift experi- ments and specific deuteration. The securinine alkaloids comprise a group of about a dozen alkaloids sharing a unique ring structure and biosynthesis (1,2). It has recently been demonstrated that securinine is a stereospecific GABA, receptor antagonist of restricted conformation (3), making it a useful tool for understanding GABA receptor topography. It was therefore of interest to assign the cmr spectra in this series in order to facilitate identification of new alkaloids and to understand better the limited conformational mobility of the alkaloids. Single-frequency off-resonance decoupling (SFORD) experiments were of limited utility in assigning resonances because the respective methylene, methine, and quater- nary carbon resonances occurred in closely spaced groups that could not be completely assigned without further experimental techniques. The lanthanide shift reagent Eu(fod), provided invaluable information, and the trends in chemical shifts throughout the series were correlated with conformation predicted by MM2 molecular mechanics calculations. Specific deuteration was helpful in assigning the resonances of dihy- drosecurinine (3). Finally, the previously assigned spectrum of indolizidine (4) pro- vided confirmation. Assignments are tabulated in Table 1 for securinine (l), al- losecurinine (2), 14,15-dihydrosecurinine (3), and 14,15-dihydroallosecurinine (4): Detailed comparisons ofpredicted and observed shifts are not presented for all cases, be- cause a simple graphical comparison of the induced shifts of each set of two or three am- biguous resonances gave identical asignments. The distance term (r3) in the McCon- nell-Robertson equation (5,7) is dominant over the angle term (cos 2 8) for the sec- urinine alkaloid structures.