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A new secopyrrolizidine alkaloid, acetylanonamine, was isolated from Senecio anonymus. The structure was established by high resolution nmr (1H-1H COSY and 1H-13C HETCOR), ms, comparison of these spectral data with those of anonamine, and synthesis of 1 from 2.

(-)- and (+)-trachelanthic and (-)- and (+)-viridifloric acids were synthesized and their isopropylidene derivatives were regiospecifically coupled, at C-9, with (-)-retronecine obtained by hydrolysis of monocrotaline, isolated from Crotalaria spectabilis. Hydrolysis, followed by oxidation, led to the N-oxides of indicine, intermedine, lycopsamine, and the new nonnatural product, respectively. Each of these analogues was screened in the P388 lymphocytic leukemia system at the same time as indicine N-oxide, and the results were compared. Other related analogues were prepared and similarly screened and the results compared with those from indicine N-oxide.

The C-9 and C-7 monoesters and C-7, C-9 diesters of heliotridine with (S)-(+) and (R)-(-)-2-hydroxy-2-phenylbutyric acid were prepared, converted into their N-oxides, and compared with the corresponding C-9 monoesters of retronecine in the in vivo P388 lymphocytic leukemia screen. Relative in vitro cytotoxicities of some of the free bases and their corresponding N-oxides were also measured against the A204 rhabdomyosarcoma cell line by using the soft agar colony forming assay. Stereochemistry at C-7 of the necine and at C-2' of the necine acid appears to have a significant effect on the antitumor activity in this system. In the heliotridine series, the configuration of the necic acid has a pronounced effect on the site selectivity (C-7 vs C-9) in esterification with carbodiimidazole. An explanation for this site selectivity is offered.

Ten 12-membered macrocyclic pyrrolizidine alkaloids, all of them esters of the necines, retronecine or otonecine, have been isolated from Senecio anonymus. The separation, carried out by droplet counter-current chromatography, afforded senecionine [1], integerrimine [2], retrorsine [3], senkirkine [5], neosenkirkine [6], otosenine [10], hydroxysenkirkine [7], and a new alkaloid given the trivial name anonamine [9]. Traces of usaramine [4] and another new alkaloid, hydroxyneosenkirkine [8], were detected by 1H nmr. In addition, the previously unreported 3a beta-hydroxy-4-ethoxy-2,6-perhydroindoledione [11] was isolated. X-ray structures were obtained for neosenkirkine [6], hydroxysenkirkine [7], anonamine [9], and [11]. 1H-13C heteronuclear shift correlated nmr (HETCOR) provided unambiguous chemical shift assignments for 13C-nmr data. Antitumor activity was assayed using the A204-rhabdomyosarcoma cell line in soft agarose.

Reinvestigation of Cynoglossum creticum led to the isolation of the previously reported echinatine [1] and heliosupine [2] as well as rinderine [3], 7-angelylheliotridine [4] and a new alkaloid, cynoglossamine [5]. The structures have been determined by spectral means (ir, ms, 1H-13C HETCOR nmr), comparison with literature data and authentic samples, and/or syntheses. In addition, 1 and all three of its isomers 3, 6, and 7 and other semisynthetic analogues (8-13) were prepared and characterized.

lambda(Mo K alpha) = 0.71069 A, T = 298 K. Anonamine (I) (12,21-dihydroxy-4-methyl-4,8-secosenecionan-8,11,16-trione): C19H27NO7, Mr = 381.2, monoclinic, C2, a = 24.247 (7), b = 8.766 (2), c = 9.072 (1) A, beta = 99.21 (2) degrees, U = 1903.3 (8) A3, Z = 4, Dm = 1.32 (1), D chi = 1.330 g cm-3, mu(Mo K alpha) = 1.09 cm-1, F(000) = 816. Neosenkirkine (II) (12-hydroxy-4-methyl-4,8-secosenecionan-8,11,16-trione): C19H27NO6, Mr = 365.2, monoclinic, C2, a = 24.45 (1), b = 8.781 (2), c = 9.029 (2) A, beta = 98.99 (3) degrees, U = 1915 (1) A3, Z = 4, Dm = 1.27 (1), D chi = 1.267 g cm-3, mu(Mo K alpha) = 1.01 cm-1, F(000) = 784. Hydroxysenkirkine (III) [12,18-dihydroxy-4-methyl-4,8-secosenecionan-8, 11,16-trione-methanol (1/1)]: C19H27NO7.CH3OH, Mr = 413.2, orthorhombic, P2(1)2(1)2(1), a = 9.052 (3), b = 13.150 (4), c = 17.404 (8) A, U = 2071 (1) A3, Z = 4, Dm = 1.33 (1), D chi = 1.325 g cm-3, mu(Mo K alpha) = 1.10 cm-1, F(000) = 888. Full-matrix least squares refinement converged at R values of 0.042, 0.043 and 0.051 for 3163, 2894 and 2896 reflections for (I), (II), (III), respectively. All three crystals exhibit hydrogen bonds, including intramolecular O11...HO12 and intermolecular O8...HO12. In addition, intermolecular hydrogen bonds appear in (I) between O21...HO21' and in (III) between O8...HOCH3. The observed N...C8 distances across the eight-membered otonecine rings were 2.200, 2.245 and 1.712 A in (I), (II) and (III) respectively.

Heliotropium rotundifolium was shown to contain, in addition to the previously isolated europine [1], three other alkaloids: heliotrine [2], lasiocarpine [3], and a new alkaloid identified as 5'-acetyleuropine [4]. The alkaloids were isolated by dccc and the structures established by spectroscopic means (1H and 1H- 13CHETCOR nmr and ms), physical properties (melting points and/or optical rotations), comparison with authentic samples, or by semi-synthesis.

The application of capillary supercritical fluid chromatography (SFC) for the separation of pyrrolizidine alkaloids (PAs) is examined. Most of these compounds are powerful toxins. Because they are present in at least 3% of all flowering plants, they are responsible for serious losses of livestock and human disease. Capillary SFC, with its high separation efficiency, is shown to be an excellent method for the chromatographic analysis of complex PA mixtures. Complete separation of the PAs of the retronecine and otonecine family has been achieved by pressure-programmed capillary SFC. The operating conditions are mild enough to prevent thermal decomposition of the alkaloids during analysis.