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A comprehensive GC-MS analysis of 8 Ipomoea species belonging to the subgenus Quamoclit, section Mina revealed that the members of this taxon form combinations of two necine bases with rare necic acids resulting in unique pyrrolizidine alkaloids. The occurrence and diversity of these metabolites show remarkable variations: Some species, especially Ipomoea hederifolia and Ipomoea lobata, are able to synthesize a large number of alkaloids whereas others, especially Ipomoea coccinea and Ipomoea quamoclit, are poor synthesizers with only a few compounds. However, these metabolites are apparently chemotaxonomic markers of this infrageneric taxon in general. They represent either esters of (-)-platynecine (altogether 48 ipangulines and 4 further esters including results of a previous study) or esters of (-)-trachelanthamidine, an additional novel structural type called minalobines (altogether 21 alkaloids). Both types are characterized by section-specific rare necic acids, e.g., ipangulinic/isoipangulinic acid, phenylacetic acid. The alkaloids of Ipomoea cholulensis, I. coccinea, I. hederifolia, Ipomoea neei, and Ipomoea quamoclit were mono and diesters of platynecine. Minalobines turned out to be metabolites of I. lobata (Cerv.) Thell. (syn.: Mina lobata Cerv.) lacking ipangulines. The major alkaloid of this species, minalobine R, has been isolated and identified as 9-O-(threo-2-hydroxy-2-methyl-3-phenylacetoxy-butyryl)-(-)-trachelanthamidine on the basis of spectral data. Apparently only two of the species included in this study, Ipomoea cristulata and Ipomoea sloteri, are able to synthesize both, ipangulines as well as minalobines. Minalobine O could be isolated as a major alkaloid of I. cristulata, its structure has been established as 9-O-(erythro-2-hydroxy-2-methyl-3-tigloyloxy-butyryl)-(-)-trachelanthamidine on the basis of spectral data.

Phytochemical investigation of Osyris alba L. (Santalaceae) of Jordanian origin resulted in the isolation and identification of one new pyrrolizidine alkaloid, osyrisine (1), together with 16 other known compounds. The structures of all compounds were established on the basis of spectroscopic analysis. Osyrisine, catechin, and catechin-3-O-α- l-rhamnopyranoside exhibited a significant level of antiparasitic activity against two parasites, Entamoeba histolytica and Giardia intestinalis.

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.

A first stereodivergent strategy for the asymmetric synthesis of all stereoisomers of 1-hydroxymethylpyrrolizidine alkaloids is developed using an asymmetric self-Mannich reaction as a key step. An anti-selective self-Mannich reaction of methyl 4-oxobutanoate with the PMP-amine catalyzed by a chiral secondary amine is successfully optimized for the asymmetric synthesis of (+)-isoretronecanol and (-)-isoretronecanol. A syn-selective self-Mannich reaction catalyzed by proline is utilized for the asymmetric synthesis of the diastereomer, (+)-laburnine, and its enantiomer, (-)-trachelanthamidine.

An asymmetric, organocatalytic, one-pot Mannich cyclization between a hydroxylactam and acetal is described to provide fused, bicyclic alkaloids bearing a bridgehead N atom. Both aliphatic and aromatic substrates were used in this transformation to furnish chiral pyrrolizidinone, indolizidinone, and quinolizidinone derivatives in up to 89% yield and 97% ee. The total syntheses of (-)-epilupinine, (-)-tashiromine, and (-)-trachelanthamidine also achieved to demonstrate the generality of the process.

Short and concise total asymmetric syntheses of (-)-isoretronecanol and (-)-trachelantamidine are reported. Oxidative cleavage of tert-butyl (S,S,S,Z)-7-[N-benzyl-N-(α-methylbenzyl)amino]cyclohept-3-ene-1- carboxylate, followed by hydrogenolysis promoted

Six pyrrolizidine alkaloids were isolated from the whole herb of Liparis nervosa together with two previously known ones. Their structures were elucidated by extensive spectroscopic analyses and chemical reactions. The cytotoxicity of the isolates was eva

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

A series of pyrrolizidine esters, amides, and ureas was prepared and tested for 5-HT4 and 5-HT3 receptor binding, 5-HT4 receptor agonism in the rat tunica muscularis mucosae (TMM) assay, and for 5-HT3 receptor-mediated functional antagonism in the Bezold-Jarisch reflex assay. Several pyrrolizidine derivatives were identified with high affinity for the 5-HT4 receptor, including benzamide 12a (SC-53116), a potent and selective 5-HT4 partial agonist that exhibits efficacy in promoting antral contractions and activity in promoting gastric emptying in canine models. Also discovered were 5-HT4 receptor antagonists, including imidazopyridine amide 12h (SC-53606), which is a potent and selective 5-HT4 receptor antagonist with a pA2 value of 8.13 in the rat TMM assay. N-Methyl indole ester 13d was identified as a potent 5-HT 4 antagonist with a pA2 value of 8.93. High selectivity was observed for these pyrrolizidine derivatives versus other monoamine receptors, including 5-HT1, 5-HT2, D1, D 2, α1, α2, and β receptors. 2006 American Chemical Society.

In the presence of triethylborane, N-allylic α-iodoacetamides underwent atom transfer cyclization to give β-iodomethyl-γ-lactams in high yields.

The pyrrolizidine precursors 13 and 14 are obtained both by enolate Clalsen 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 21 a 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.

An efficient route to the pyrrolizidine ring system has been developed. The method, which uses N-acetyl and N-propionyl anion cyclisation reactions as the key steps has provided the natural pyrrolizidines (-)-(1R, 8S)-1-hydroxypyrrolizidine (10), (-)-pyrrolizidin-1-ene-3-one (13), (±)-trachelanthamidine (18) together with a range of 2-methyl substituted pyrrolizidine-3-ones.

A new method for the synthesis of five-membered lactams by ruthenium-catalyzed chlorine atom transfer cyclizations of N-allylic α-chloro-α-thioacetamides and the application of the method to the synthesis of the title alkaloids are described.A benzene sol

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(-)-Trachelanthamidine, 12, and (-)-isoretronecanol, 14, have been prepared from (S)-2-pyrrolidineacetic acid by α-allylation using either a Claisen rearrangement or direct enolate alkylation followed by cleavage of the side-chain and cyclisation

The α-allyl homoproline ester 8, obtained by Claisen rearrangement of the allyl ester 7 or direct C-allylation of the homoproline methyl ester 9 has been converted into (-)-trachelanthamidine 4a and (-)-isoretronecanol 4b while allylation of the enolate derived from the lactone 13a followed by related transformations leads stereospecifically to turneforcidine 12.

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Orthoester Claisen rearrangement of (2S)-2--pyrrolidine derived from (S)-proline gave (2S)-2--N-(t-butoxycarbonyl)-pyrrolidine which is ready for further elaboration directed to necine base skeleton.Title compounds have been synthesized using this key intermediate.

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

Dieckmann cyclisation of (S)-N,2-di(carboethoxymethyl)pyrrolidine, made from (S)-proline, gave (8S)-1-carboethoxypyrrolizidin-2-one, which was then converted into (-)-isoretronecanol, (-)-trachelanthamidine, and (-)-supinidine.

Isolation and structure determination of the minor alkaloids of Heliotropium curassavicum are described.These include the new pyrrolizidine alkaloids, heliocurassavine , heliocoromandaline , heliocurassavicine , heliocurassavinine , curassavinine , coromandalinine , heliovinine and curassanecine .Structures were established by high resolution 1H NMR, mass spectrometry and paper electrophoresis of the alkaloids and their hydrolysis products. - Key Word Index-Pyrrolizidine alkaloids; heliocurassavine; heliocurassavinine; heliocurassavicine; heliocoromadaline; curassavinine; coromandalinine; heliovinine; curassanecine.

Regiospecific 1,3-dipolar cycloaddition of ethyl propiolate to the NO-diformyl derivative (1) of natural (-)-4-hydroxy-L-proline followed by stereospecific hydrogenation gave ethyl (+)-6α-hydroxy-β-pyrrolizidine-1α-carboxylate (4).Confirmation of the abso

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