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A novel rearrangement of 2-vinyl aziridine 2-carboxylates to unusual chiral cyclic sulfoximines is described herein. The method allows the synthesis of substituted cyclic sulfoximines in high yields with complete stereocontrol, displaying a wide substrate scope under mild conditions. Further development of a one-pot process directly from sulfinimines shows the synthetic applicability of this protocol, providing access to complex chiral sulfoximines in only two steps from commercially available aldehydes. A mechanistic hypothesis and synthetic application in the formal synthesis of trachelanthamidine by transformation of a cyclic sulfoximine into a pyrroline is also disclosed.

Curassavine was isolated as a yellowish viscous liquid and identified as (ester of trachelanthamidine and 3-carboxy-4-methylhexane-2,3-diol) by the aid of mass spectrometry (MS) and Nuclear Magnetic Resonance spectroscopy (1H and 13C-NMR).Considerable mortality was evident after the treatment. With regard to the larvicidal activity, the obtained data showed mortality percentages between 4 and 24 % using concentrations between 100 and 500 mg/ml after 3 days. The mortality increased to reach 8 and 86 % for the same concentrations within 5 days. LC50 was 288.4 mg/ml. Concerning the pupicidal activity, no effect using concentrations between 100 and 500 mg/ml within 2 days; while they showed mortality percentages between 8 and 60 % within 5 days. LC50 was 512.9 mg/ml. On the other hand, Curassavine caused mortality percentages among larvae and pupae of Culex pipiens between 12 and 84 % using concentrations between 100 and 500 µg/ml after one day. While they showed mortality percentages between 16 and 100 % within 2 days; Value of LC50 was 147.9 µg/ml.

A successful application of the Wittig-olefination–Claisen rearrangement protocol gave the allyl vinyl ether 12 , which was efficiently converted into (−)-tashiromine alkaloids in a short sequence with high overall yield.

A novel rearrangement of 2-vinyl aziridine 2-carboxylates to unusual chiral cyclic sulfoximines is described herein. The method allows the synthesis of substituted cyclic sulfoximines in high yields with complete stereocontrol, and tolerates a wide substrate scope. A one-pot process starting directly from sulfinimines provides access to complex chiral sulfoximines in only two steps from commercially available aldehydes. A mechanistic hypothesis and synthetic application in the formal synthesis of trachelanthamidine, by transformation of a cyclic sulfoximine into a pyrroline, is also disclosed.

A common and short stereoselective route is described for the formal synthesis of pyrrolizidine alkaloids, (−)-isoretronecanol and (−)-trachelanthamidine. An approach to the synthesis of indolizidine alkaloids (−)-5-epitashiromine and (−)-tashiromine utilizing ring closing metathesis is also described starting from commercially available and inexpensive l -proline.

(-)-Tashiromine (XV), (-)-trachelanthamidine (XVI) and (-)-epilupinine (XVII) can be easily prepared from precursors (IIa), (V), and (IXa).

Base-induced coupling/cyclization stepwise [3+2] annulation of α-sulfonylacetamide with (Z)-2-bromoacrylates yielded polysubstituted pyroglutamates with three contiguous chiral centers with trans-trans orientation in a one-pot synthesis. The pyrrolizidine skeleton was obtained via an intramolecular cyclization. This facile strategy was used to synthesize (±)-trachelanthamidine.

金沢大学ナノ生命科学研究所 / 金沢大学医薬保健研究域薬学系, Synthesis of (-)-trachelanthamidine, one of the pyrrolizidine alkaloids, has been achieved by using a single electron transfer reaction of 2-(2-acetoxyethenyl)-N-(trichloroacetyl)pyrrolidine in boiling 1,4-dimethylpiperazine as the key step. © 2008 Elsevier Ltd. All rights reserved.

A stereoselective synthesis of (-)-trachelanthamidine has been developed, employing a palladium-catalysed cyclisation as the key step.

The pyrrolizidine precursors 13 and 14 are obtained both by enolate Claisen rearrangement of the homoproline allyl ester 12 and by direct allylation of N-protected homoproline ethyl ester 15. In both cases, the reactions show poor levels of stereoselectivity. Reduction gives the corresponding alcohols 20a and 21a which are separated and subsequently elaborated to (-)-trachelanthamidine 24 and (-)-isoretronecanol 25 respectively via reductive alkene cleavage, mesylation and spontaneous cyclisation following N-deprotection. The chiral integrity of the original proline-derived asymmetric centre is preserved throughout. A similar enolate allylation gives, with high stereoselectivity, the homologue 34 of the Geissman–Waiss lactone 32, which is similarly transformed into (±)-turneforcidine 31.

The palladium-catalyzed intramolecular aminoalkynylation of terminal olefins is operationally simple and can be applied to tosyl amides, carbamates, and ureas to give five- or six-membered heterocyclic rings.

Rhodium-catalyzed silylformylation and amidocarbonylation are applied to the syntheses of pyrrolizidine alkaloids, (±)-isoretronecanol and (±)-trachelanthamidine, from 5-ethynyl-2-pyrrolidinone.

The pyrrolizidine precursors 13 and 14 are obtained both by enolate Claisen rearrangement of the homoproline allyl ester 12 and by direct allylation of N-protected homoproline ethyl ester 15. In both cases, the reactions show poor levels of stereoselectivity. Reduction gives the corresponding alcohols 20a and 21a which are separated and subsequently elaborated to (-)-trachelanthamidine 24 and (-)-isoretronecanol 25 respectively via reductive alkene cleavage, mesylation and spontaneous cyclisation following N-deprotection. The chiral integrity of the original proline-derived asymmetric centre is preserved throughout. A similar enolate allylation gives, with high stereoselectivity, the homologue 34 of the Geissman–Waiss lactone 32, which is similarly transformed into (±)-turneforcidine 31.

Base-induced coupling-cyclization stepwise [3+2] annulation of α-sulfonylacetamide with (Z)-2-bromoacrylate yielded the polysubstituted pyroglutamate with three contiguous chiral centers with trans-trans orientation in a one-pot synthesis. The pyrrolizidine skeleton was obtained via the ring-closing metathesis (RCM) method. This facile strategy was used to synthesize (′)-trachelanthamidine.

( + -Trachelanthamidine and ( + -isoretronecanol have been synthesized via reductive cyclisation of the phenylthioacetylene imid 5 .

Fourteen species of Heliotropium from Mexico and Texas contained 3-7 necines per species. In most cases there were no qualitative differences in th

The title compounds are prepared in five steps from N-2-bromo ethyl succinimide.

The qualitative and quantitative compositions of necines in plants of 20 Heliotropium species collected in Mexico and the U.S.A. and one species from Spain are reported. Trachelanthamidine, supinidine and retronecine were found in all species after hydrolysis of their alkaloids; lindelofidine was detected in most species, whereas heliotridine only in four. Trachelanthamidine, lindelofidine, and supinidine were dominant in four, two and one species, respectively; retronecine was dominant in 15 species, whereas heliotridine only in one. The dominant necine in H. ternatum was either retronecine or lindelofidine depending on the collection locality. Qualitative as well as quantitative differences depending on the collection locality were found in H. curassavicum . Plants from Oaxaca, Mexico, contained lindelofidine and a pyrrolizidine-diol as major necines, trachelanthamidine as minor, and traces of retronecine. Plants originating from two other localities contained trachelanthamidine (dominant), retronecine, and supinidine. The necine patterns found in the examined species differ significantly from those previously reported for 21 species mainly collected in Asia, the Middle East and Australia.

Vinylaziridine 2 underwent alkylative ring opening with trimethylsilyl iodide to furnish supinidine ethyl ester 4 from which supinidine 5, isoretronecanol 7, and trachelanthamidine 9 were synthesized stereoselectively.

La methoxylation electrochimique de l'ester dimethylique, pyrrolidide de l'acide ethanetricarboxylique-1,1,2, conduit au derive methoxy-2 pyrrolidide correspondant (I). L'amidoalkylation intramoleculaire de (I) conduit au squelette pyrrolizidinique

The root of Eupatorium maculatum L. has been examined and found to contain at least four alkaloids. The major base was found to be echinatine, while the second one in importance has been identified as the non-esterified trachelanthamidine. The remaining two alkaloids are probably also of the pyrrolizidine type, but their structures could not be determined due to paucity of material.

A facile synthesis of the pyrrolizidine alkaloids, (±)-supinidine (14) and (±)-trachelanthamidine (8) was achieved by employing aziridine as the reactive species.

Heliotropium curassavicum var. argentinum and var. H. curassavicum have been investigated chemically and a new pyrrolizidine alkaloid has been isolated from both. The latter variety also yielded a related acetylated, 9-(3′-isovaleryl)viridifloryl retronecine alkaloid. The structures have been established by spectroscopic means. Trachelanthamidine was the dominant base found in previous studies of H. curassavicum whereas retronecine is the necine present in the alkaloids now reported.

Pyrrolidon (I) wird in das Thioderivat (Ib) ubergefuhrt und dann mit Bromessigester (II) zu (III) substituiert wird.

Vinylaziridine 2 underwent alkylative ring opening with trimethylsilyl iodide to furnish supinidine ethyl ester 4 from which supinidine 5, isoretronecanol 7, and trachelanthamidine 9 were synthesized stereoselectively.

The syntheses of pyrrolizidine alkaloids, (±)-trachelanthamidine, (±)-isoretronecanol, and (±)-supinidine were achieved via a carbon–carbon bond formation at the α-position to the nitrogen by employing an intramolecular carbenoid displacement (ICD) reaction as a key step.

(–)-Trachelanthamidine was synthesised in an optically active form from L-prolinol, using olefin cyclisation initiated by an α-thiocarbocation as the key step.

The main alkaloids of Heliotropium curassavicum Linn. have been identified. They are curassavine(4), an ester of trachelanthamidine with a new acid, curassavic acid [2-hydroxy-2-(1-hydroxyethyl)-3- methylpentanoic acid] (3), coromandaline (1), an ester of trachelanthamidine with (+)-viridifloric acid (previously unknown in nature), and heliovicine (2), an ester of trachelanthamidine with the uncommon (-)-enantiomer of trachelanthic acid.

Aus dem Cyclopropyl-pyrrolin (I) erhalt man beim Erhitzen mit Ammoniumchlorid das Pyrrolizidin (II), das bei der katalytischen Hydrierung zu den gesattigten Estern (III) fuhrt.

A synthesis of (±)-trachelanthamidine (5) is described usign enzymes and physiological conditions; this synthesis is patterned on the likely biosynthetic pathway to pyrrolizidine alkaloids from homospermidine (1).

(–)-Trachelanthamidine was synthesised in an optically active form from L-prolinol, using olefin cyclisation initiated by an α-thiocarbocation as the key step.