THE STRUCTURE OF SECURININE

This paper reports the structural elucidation of securinine, a lactonic alkaloid of composition C₁₃H₁₅O₂N (VII; for formulas, see the Chinese text). Hydrogenation of securinine showed the presence of two double bonds, the attendant shifts of infrared carbonyl absorption being indicative of a conjugated five-membered lactone. Alkali fusion of securinine furnished a 63% yield of o-hydroxyphenylacetic acid (I), which was later found to be obtainable under much milder conditions. Combined with ultraviolet (255mμ, log ? 4.2) and NMR (Fig. 1) evidence, partial structure II can be advanced, since pKa values precluded the possibility of III. As seen from the molecular formula, securinine should be tetracyclic. The failure to detect simple aldehydes or ketones (except for a low yield of glyoxal) from ozonolysis as well as the absence of N- and C-methyl groups strongly indicated the tertiary amino nitrogen (no N-H band) to be shared by two rings. Securinine and tetrahydrosecurinine (IX) can be dehydrogenated with mercuric acetate, the amounts of mercurous acetate precipitate corresponded to the introduction of one double bond. Partial formulas IV to VI were considered for the bicyclic hetero-rings, since bridged structures would violate Bredt's rule. Smaller hetero-rings failed to account for the stability of securinine upon prolonged refluxing in conc. hydrochloric acid, while larger rings were out of the question with a total of only 13 carbon atoms. Since tetrahydrosecurinine can be oxidized to give a six (or higher)-membered lactam (IR 6.01μ), partial structure VI had to be discarded. Partial structure IV had to share five carbon atoms of II while the latter can donate a maximum of four. This leaves V as the only alternative, leading to VII as the proposed complete structure. Formation of I from VII can be rationalized as the result of decomposition of XI through a reversed Mannich-type process. Lithium aluminum hydride reduction of securinine gave securininediol (XIII), which furnished salicylic acid (XV) upon alkali fusion. This can be regarded as a mechanistically similar process. The nitrogen-containing fragment from alkali fusion of securinine has been identified as △¹-tetrahydropyridine (XII) via hydrogenation to piperidine. Hofmann degradation of securinine methiodide (XVI) gave o-hydroxyphenylacetic acid (I) and N-methyltetrahydropyridine XVII. These two pieces of evidence constitute conclusive proof of our proposed structure VII. The NMR spectrum was discussed. Diamagnetic shielding of C10 proton (7.1τ) by the double bond allowed the assignment of relative configurations as shown by Ⅶa. The proposal of Ⅶa as representing the absolute configuration, however, is to be regarded as highly speculative. During the draft of this paper, a short communication1181 came to our notice which proposed the same structure for securinine after degradative studies along different lines of attack.