We describe the isolation from Corydalis claviculata (L.) DC. and the structure determination of the three new alkaloids dioxocularine - 1, norsecocularine 2 and viguine 1.Recent studies carried out in our laboratories on the alkaloids of plants of the genera Sarcocapnos and Corydalis (Fumariaceae) have led to the isolation of the first members of two new groups of cularine-related alkaloids, the 3.4-dioxo-2 cularinesl and the secocularines . Now we wish to describe the isolation from Corydalis claviculata (L.) DC. of a new member of each group, namely dioxocularine - 1 and norsecocularine p. In addition we have also isolated from the same source a non-phenolic N-benzyltetrahydroisoquinoline alkaloid, viguine 3. Dioxocularine 1 is a very minor component of C.Claviculata (L.) DC. being obtained as red crystals, mp 212-214'C (EtOH). Its PMR spectrum (250 MHz,CDC13,& ) (Figure I) suggested a 3.4-dioxocularine structure exhibiting the presence of five aromatic protons, three methoxyl groups and one highly deshielded N-methyl group; no signals were observed in the aliphatic part of the sepctrum. Also very useful for establishing the structure of this compound was the CMR spectrum (62.83 MHz, CDCI3,& 1, which revealed the presence of two carbonyl groups (singlets at 175.31 and 156.901, nine quaternary sp2 carbons (singlets at 156.86, 151.36, 148.93, 146.86, 141.40, 134.34, 129.58, 121.89 and 119.961, five methine sp 2 carbons (doublets at 126.72, 118.12, 113.92, 111.62 and 105.24). three methoxy groups (quartets at 56.65, 56.38 and 56.29) and an N-methyl group (quartet at 32.83). Moreover the UV spectrum, which remained unchanged upon addition of acid and base, showed bands at ~ii'~ (log c ): 224 (4.40). 260 (4.15). 304 (3.96), 340 (4.06) and 452 (3.75) nm characteristic of the highly conjugated system of a 3,4-dioxocularine, and the IR spectrum (KBr) exhibited strong absorption at 1680 cm-' due to a conjugated carbonyl group. Further proof was obtained from the mass spectrum; in addition to the molecular ion at m/z 367 (100) which confirmed the molecular formula C20H17N06 deduced by elemental analysis, it showed significant peaks due to correlative losses of carbonyl and methyl fragments at m/z 339 (31), 324 (381, 296 (34), 281 (14). 266 (6). 238 (17) and 210 (14). Finally, structure 1 for dioxocularine was confirmed by a PMR nOe 3 difference study (Figure I) and by direct comparison with synthetic material . Norsecocularine 2, obtained as white crystals, mp 203-205'C (benzene), is also a minor component in the plant. Its molecular formula, C20H23N04, was established by high resolution MS which showed the molecular ion at 341.1625 (calculated 341.1627).2 The UV spectrum, characteristic of a secocularine structure , showed absorption bands at A,,, EtOH (log E ): 220 (4.23), 296 sh (3.68) and 316 13.76) nm and no change with acid or base. In spite of its non-phenolic nature, the IR spectrum 1 exhibited absorption at 3400 cm' , revealing the presence of an -NH group. Its PMR spectrum (250 MHz, CDC13,6 ) (Figure 11) showed the characteristic aromatic part of a secocularine with two ABq, one of them with a very large coupling constant, and two one-proton singlets. In addition, signals in the aliphatic part suggested that the molecule possessed a -CH2CH2NHMe, which was also supported by the presence of a base peak in the mass spectrum at mlz 44 (cH~=NHM~)+. Other signals were observed at mlz 341 (M+, I), 298 (4). 297 (2). 165 (3), 152 (41, 139 (4), 115 (2). Structure - 2 for this compound was confirmed by its transformation into secocularine 4 (which has been isolated in our laboratory from Sarcocapnos 2 crassifolia (L.) DC. ) via N-methylation with H-COH/NaBH4. Comparison of the PMR data of the two compounds allowedus to assign all of its resonances as shown in Figure 11.The third alkaloid, viguine 3, was isolated as white crystals, mp 63-64nC ( benzenelhexane). Its molecular formula, C18H1gN03, was established by elemental analysis of its hydrochloride (mp 232-233OC, EtOH) and confirmed by MS, which showed the molecular ion at mlz 297 (23) with other significant peaks at 176 EtOH. (23), 148 (63) and 121 (100). The UV spectrum showed absorption bands at Amax . 224 and 294 nm and no change was observed upon addition of acid or base. The most significant signals of its PMR spectrum (250 MHz, CDC13,6 ) (Figure 111) were a pair of doublets due to a para-disubstituted benzene ring and, in the aliphatic part, two singlets for two isolated methylene groups and two triplets for a -CH2CH2- system, which strongly suggested an N-benzyltetrahydroisoquinoline skeleton for this compound. Further proof for structure 3 came from a PMR nOe difference study and direct comparison with synthetic material, which was easily obtained by coupling of 6,7-methylenedioxy-3,4-dihydroisoquinoline4 (norhydras-5 tinine) 5 and 4-methoxybenzylchloride 5, followed by treatment with NaBH4.