Pyrrolizidine Ring System Research Articles

Asymmetric syntheses of (−)-hastanecine, (−)-turneforcidine and (−)-platynecine

Concise total asymmetric syntheses of three diastereoisomeric 1-hydroxymethyl-7-hydroxy substituted pyrrolizidines, (−)-hastanecine, (−)-turneforcidine and (−)-platynecine, are reported. The doubly diastereoselective conjugate additions of lithium (R)- or (S)-N-benzyl-N-(α-methylbenzyl)amide to tert-butyl (R,E)-4-(triethylsilyloxy)hepta-2,6-dienoate [which was prepared (in 96:4 e.r.) via Lewis acid mediated catalytic asymmetric allylation of tert-butyl (E)-4-oxobut-2-enoate] proceeded in both cases under the dominant control of the lithium amide reagent. Subsequent diastereoselective enolate allylations installed the required stereogenic centres, and the pyrrolizidine ring system was rapidly accessed by a two-step protocol (viz. ozonolysis and one-pot hydrogenolysis/double reductive cyclisation), to complete the asymmetric syntheses of (−)-hastanecine, (−)-turneforcidine and (−)-platynecine in 17, 8 and 24% overall yield, respectively, in eleven steps from commercially available 2,2-dimethoxyacetaldehyde in each case.

Ether bridge formation in loline alkaloid biosynthesis

Lolines are potent insecticidal agents produced by endophytic fungi of cool-season grasses. These alkaloids are composed of a pyrrolizidine ring system and an uncommon ether bridge linking carbons 2 and 7. Previous results indicated that 1-aminopyrrolizidine was a pathway intermediate. We used RNA interference to knock down expression of lolO, resulting in the accumulation of an alkaloid identified as exo-1-acetamidopyrrolizidine based on high-resolution MS and NMR. Genomes of endophytes differing in alkaloid profiles were sequenced, revealing that those with mutated lolO accumulated exo-1-acetamidopyrrolizidine but no lolines. Heterologous expression of wild-type lolO complemented a lolO mutant, resulting in the production of N-acetylnorloline. These results indicated that the non-heme iron oxygenase, LolO, is required for ether bridge formation, probably through oxidation of exo-1-acetamidopyrrolizidine.

Methyl 11-hydroxy-9-[1-(4-methoxyphenyl)-4-oxo-3-phenoxyazetidin-2-yl]-18-oxo-10-oxa-2-azapentacyclo[9.7.0.01,8.02,6.012,17]octadeca-12(17),13,15-triene-8-carboxylate

In the title compound, C34H32N2O8, one of the pyrrolidine rings in the pyrrolizidine ring system adopts a twist conformation, whereas the other ring adopts an envelope conformation (C atom as flap). The five-membered ring in the indene ring system and the fused furan ring also adopt envelope conformations (C and O atoms as flaps, respectively). The β-lactam ring makes dihedral angles of 23.41 (2) and 25.98 (2)°, respectively, with the attached meth­oxy­phenyl and phen­oxy rings. The mol­ecular conformation is stabilized by an intra­molecular O—H⋯N hydrogen bond, generating an S(5) motif. In the crystal, mol­ecules are linked into C(12) chains running along the a axis by C—H⋯O hydrogen bonds. The structure is further consolidated by weak inter­molecular C—H⋯π and π–π inter­actions [centroid–centroid distance = 3.7987 (14) Å].

2′-Hydroxymethyl-1′-(4-methylphenyl)-2′-nitro-1′,2′,5′,6′,7′,7a′-hexahydrospiro[indoline-3,3′-pyrrolizin]-2-one

In the title compound, C22H23N3O4, the tolyl ring is almost perpendicular [83.86 (7)°] to the best plane through the eight atoms of the pyrrolizidine ring system. The mol­ecular conformation is stabilized by an intra­molecular O—H⋯O hydrogen bond. The crystal packing features inversion dimers with R 2 2(8) motifs linked by pairs of N—H⋯O hydrogen bonds.

Cascade cyclization intermolecular dipolar cycloaddition by multi-component couplings—synthesis of indolizidines and pyrrolizidines

A three-component coupling reaction of a primary amine (an amino-acid or amino-ester or hydroxylamine), an alkene or alkyne dipolarophile and an aldehyde bearing a halide as a leaving group has been developed. Condensation of the amine with the aldehyde and cyclization (intramolecular N-alkylation) provides, after decarboxylation or deprotonation, a cyclic azomethine ylide (or nitrone) that undergoes intermolecular dipolar cycloaddition with the dipolarophile. This sets up, in a single step, the bicyclic indolizidine or pyrrolizidine ring system, depending on the length of the tether between the aldehyde and the halide. The reaction is successful with stabilized and non-stabilized azomethine ylides that result from using primary amino-esters or amino-acids, respectively.

Survey of Chemical Syntheses of the Pyrrolizidine Alkaloids Turneforcidine and Platynecine

The necine bases turneforcidine and platynecine have inspired a great deal of synthetic effort. Key challenges include the construction of the bicyclic pyrrolizidine ring system and controlled introduction of three contiguous stereocenters. This review will survey the many diverse strategies by which these natural products have been synthesized.

1′-(4-Methoxybenzoyl)acenaphthene-1-spiro-3′-pyrrolizidine-2′-spiro-3′′-1H-indole-2,2′′(1H,3′′H)-dione

The N—C and C—C bond distances in the pyrrolizidine moiety of the title compound, C33H26N2O4, are slightly longer than the normal values. This is due to the steric forces caused by bulky substituents on the pyrrolizidine ring system. The acenaphthene ketone O atom is −0.214 (3) Å from the acenaphthene plane, while the indole ketone O atom is displaced by only 0.004 (3) Å from the indole plane. The molecular structure is stabilized by intramolecular C—H⋯O interactions. The crystal packing is stabilized by C—H⋯O intermolecular interactions.

A biomimetic synthesis of the pyrrolizidine ring by sequential intramolecular cyclizations

The pyrrolizidine ring system is generated from an acyclic amide in an acid-catalyzed cyclization in one laboratory operation.

ChemInform Abstract: Addition of a Chiral Boron Enolate to Cyclic N‐Acyliminium Ions. Stereocontrolled Synthesis of the Pyrrolizidine Ring System.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: An Efficient Route to the Pyrrolizidine Ring System via an N‐Acyl Anion Cyclization Process.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

An efficient route to the pyrrolizidine ring system via an N-acyl anion cyclisation process

An enantioselective route to the pyrrolizidine ring system has been developed which uses an N-acyl anion cyclisation reaction as the key step. This methodology has provided the natural pyrrolizidines (−)-(1R, 8S)-1-hydroxy-pyrrolizidine 7, (−)-pyrrolizidin-1-ene-3-one 9 and (±)-trachelanthamidine 14. Extension of the process to an N-propionyl substrate provides ready access to a series of 2-methyl pyrrolizidines.

Addition of a Chiral Boron Enolate to Cyclic N-Acyliminium Ions. Stereocontrolled Synthesis of the Pyrrolizidine Ring System

Addition of a Chiral Boron Enolate to Cyclic <i>N</i>-Acyliminium Ions. Stereocontrolled Synthesis of the Pyrrolizidine Ring System

An asymmetric approach to the pyrrolizidine ring system viaN-acetyl and N-propionyl anion cyclisation processes

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-hydroxy-pyrrolizidine (10), (−)-pyrrolizidin-1-ene-3-one (13), (±)-trachelanthamidine (18) together with a range of 2-methyl substituted pyrrolizidine-3-ones.

ChemInform Abstract: A Route to the Pyrrolizidine Ring System Using a Novel Radical Cyclization.

AbstractRing enlargement of the cyclopropanes (I) yields the pyrrolines (II) which undergo Diels‐Alder reaction with the butadiene precursor (III) to give the hexahydroindoles (IV).

A novel approach to the synthesis of 2-benzyl substituted pyrrolizidine and pyrrolizidinone ring systems

This paper reports a new method to the synthesis of 2-benzyl substituted pyrrolizidinone and pyrrolizidine ring systems, which involves the use of a vinylogous N-acyliminium ion 12 as an initiator for the intramolecular olefin cyclization and subsequent rearrangement. The total syntheses of six unnatural new pyrrolizidinone and pyrrolizidine alkaloids 1, 2, 3, 4, 5 and 16 serve as examples.

A route to the pyrrolizidine ring system using a novel radical cyclisation

A method for the construction of pyrrolizidine rings is described using a new radical cyclisation procedure, which involves generation of an allylic radical from a preformed vinylic radical followed by cyclisation of the allylic radical onto a pendant double bond.

Positive and electron capture negative ion methane chemical ionization mass spectrometry of pyrrolizidine alkaloids.

Pulsed positive and negative ion methane chemical ionization mass spectrometry of pyrrolizidine alkaloids is reported. Positive ion spectra are characterized by a high relative abundance of [MH]+ ions while the negative ion spectra exhibit ion peaks due to dissociative electron capture. Fragmentation in both positive and negative ion spectra primarily occurs at the ester groups with the positive charge residing with the pyrrolizidine ring system while the negative charge in contrast tends to reside with the necic acid moiety. Esterification at C-9 v. C-7 can be distinguished for non-cyclic esters of retronecine in the positive ion spectra.

The ketene thioacetal group as a cationic cyclization terminator. : A synthesis of the pyrrolizidine ring system.

A cationic cyclization to the pyrrolizidine ring system is reported in which a ketene thioacetal group serves as an efficient terminator for 5-membered ring formation. (±)-Supinidine is prepared using this methodology.

New approaches to the pyrrolizidine ring system: total synthesis of (.+-.)-isoretronecanol and (.+-.)-trachelanthamidine

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNew approaches to the pyrrolizidine ring system: total synthesis of (.+-.)-isoretronecanol and (.+-.)-trachelanthamidineHarold W. Pinnick and Yeong-Ho ChangCite this: J. Org. Chem. 1978, 43, 24, 4662–4663Publication Date (Print):November 1, 1978Publication History Published online1 May 2002Published inissue 1 November 1978https://doi.org/10.1021/jo00418a031RIGHTS & PERMISSIONSArticle Views311Altmetric-Citations49LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (321 KB) Get e-Alerts Get e-Alerts