Several terpenoids and the alkaloids kokusaginine [1] and flindeniamine [2] were isolated from the aerial parts of Esenbeckia belizencis (Rutaceae). Kokusaginine showed activity in the brine shrimp lethality test. The structures of the main autoxidation products derived from the natural alkaloids were established. Previous chemical work on species of Esenbeckia (Rutaceae, Rutoideae) revealed the presence of coumarins, alkaloids, and limonoids (1-3), and recently, from Esenbeckia leiocarpa, two quinolinone alkaloids considered as biological poisons were isolated (4). Chemical investigation of the organic extracts obtained from the leaves of Esenbeckia belizencis Lundell, a tree that grows in the neotropical Mesoamerican forest, allowed us to isolate decaprenol (5), β-sitosterol, caryophyllene β-oxide (6), spathulenol (7), lupenone, friedelin, friedelanol, and two alkaloids, kokusaginine [1] and flindersiamine [2] (8,9), whose structures were established by comparison of physical and spectroscopic data with those published in the literature. The structures of the alkaloids have been further confirmed by synthesis (10,11). Compounds 1 and 2 were tested for biological activity in the brine shrimp toxicity assay (12). Compound 1 was found to be mildly toxic (LC50 367 ppm), while 2 did not display toxicity (LC50 > 1000 ppm). During the course of this study, it was observed that solutions of alkaloids 1 and 2 in CHCl3 undergo partial transformation upon standing. The transformations also proceed in other solvents such as EtOAc, n-hexane-EtOAc (3:2), and Me2CO, at room temperature, in the presence or absence of Si gel, and with the necessary presence of air and light. Preparative cc allowed isolation of the main transformation products derived from 1 and 2. The product derived from 1 had the molecular formula C13H13O5N (ms and elemental analysis) corresponding to the addition of a molecule of oxygen and loss of the elements of carbon monoxide. The presence of a 2-quinolone system in the molecule was indicated by the uv absorptions at 233, 260, and 315 nm (13) and by an ir band at 1647 cm-1. A band at 1683 cm-1 suggested the presence of an α,β unsaturated aldehyde, which was confirmed by a signal at δ 10.35 in the 1H nmr. The 1H-nmr spectrum also contained signals at δ 7.25 (s, 1H, H-5) and 6.79 (s, 1H, H-8) for the isolated protons on the benzenoid ring. Three singlet Me resonances at δ 4.14, 3.96, and 3.85 indicated the 4,6,7-substitution pattern present in the starting material, 1. Therefore, this substance was established as 3-formyl-4,6,7-trimethoxy-2-quinolone [3]. The structure of the oxidation product of 2 was analogous to the oxidation product of 1, and was established as 3-formyl-4,8-dimethoxy-6,7-methylenedioxy-2-quinolone [4]. A plausible mechanism for the oxidative degradation of 1 and 2 involves the addition of oxygen to the furan ring to form the dioxetan 5. This intermediate could not be isolated but was detected by nmr in some chromatographic fractions obtained during the isolation of 3. 1H nmr analysis of these fractions showed signals for an AB system at δ 6.18 and 5.58 (1H each, J = 6 Hz), confirmed by decoupling experiments, corresponding to the acetalic and benzylic hydrogens of 5, respectively, in addition to the signals due to the product 3. Analogous intermediates have been proposed in the transformation of 2,3-dimethylbenzo [b] furane to yield 2-acetoxyacetophenone (14) and in the cycloaddition of acetophenone to furan to yield the corresponding oxetane derivative. The acetalic proton in this oxetane is located at δ 6.10 (15). Dioxetan ring opening of 5 with C-C fission (14) would lead to the dicarbonyl intermediate 6, which upon hydrolysis afforded the final products (Scheme 1). It could be expected that electron donor substituents on the heteroaromatic nucleus would enhance the rate (and yield) of the transformation. The spontaneous oxidation of natural furoquinoline alkaloids has not been previously reported. Interestingly, the products of reserpine autoxidation have recently been discussed (16).