Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• ] and procuramine (10) [13], have also attracted attention recently. Our continuing efforts to exploit enaminones as building blocks for the synthesis of alkaloids and other nitrogen-containing heterocycles have largely concentrated on targets containing indolizidine and quinolizidine backbones [14

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• Abstract The Castagnoli–Cushman reaction of 3,4-dihydroisoquinolines with glutaric anhydride, its oxygen and sulfur analogues was investigated as a one-step approach to the benzo[a]quinolizidine system and its heterocyclic analogs. An extension towards the pyrrolo[2,1-a]isoquinoline system was achieved

• . Keywords: benzo[a]quinolizidinones; Castagnoli–Cushman reaction; 3,4-dihydroisoquinolines; monocyclic anhydrides; pyrrolo[2,1-a]isoquinolinones; Introduction The benzo[a]quinolizidine ring system is an important heterocyclic framework found in natural products and prospective pharmaceuticals [1]. This

• experiments, the relative configuration of compound 21 displaying 3J1,10b = 6.4 Hz was assigned as cis, and the configuration of the compound with 3J1,10b = 6.9 Hz as the trans isomer (Table 1). As it is known, the benzo[a]quinolizidine system can exist as interconvertible conformers due to the presence of a

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• starting material was converted into bis(hydroxymethyl)quinolizidinone 56. After mesylation and the double displacement with sodium sulfide, spirothietane-quinolizidine 57 was obtained as a key intermediate. It was further applied in the total synthesis of four different natural products of Nuphar

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• -(4'-butenyl)-5-(2'-piperidyl)piperidine) (20) and virgiboidine (3-but-3-en-1-yl)decahydro-6H-1,5-methanopyrido[1,2-a][1,5]diazocin-6-one) (21), two important pharmacologically active compounds containing dipiperidine and piperidino-quinolizidine units in their structure. Starting from the monoacetate

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• from a common intermediate which featured a highly selective dihydroxylation reaction and a RCM reaction as key steps. Keywords: chiral pool; dihydroxylation; indolizidines; quinolizidine; ring-closing metathesis; Introduction Polyhydroxylated indolizidine derivatives have attracted continued

• other reasons, several novel methodologies have been developed towards the synthesis of polyhydroxylated indolizidine and quinolizidine derivatives as analogues of natural products which involved RCM [21][22][23][24], dipolar cycloaddition [25][26], nucleophilic substitution [27][28], diazo insertion

• [29], ring expansion–transannular cyclization [30], Cope–House cyclization [31], etc. as key steps. Although great advances have been made, creation of diverse entities from a single source remains important. Herein, we report a synthetic entry to some polyhydroxylated indolizidine and quinolizidine

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• afforded the carbonyl compound and the 5,6 and 6,6-ring systems of the target compounds. Toyooka and co-workers have designed a route to both enantiomers of the quinolizidine poison frog alkaloid 195C. Key to the success of their synthetic endeavour was the preparation via direct anodic oxidation of

Total synthesis of (−)-epimyrtine by a gold-catalyzed hydroamination approach

• Thi Thanh Huyen Trinh,
• Khanh Hung Nguyen,
• Patricia de Aguiar Amaral and
• Nicolas Gouault

Beilstein J. Org. Chem. 2013, 9, 2042–2047, doi:10.3762/bjoc.9.242

• -alanine. The key step to access the enantiopure pyridone intermediate was achieved by a gold-mediated cyclization. Finally, various transformations afforded the natural product in a few steps and good overall yield. Keywords: epimyrtine; gold; gold catalysis; heterocycles; hydroamination; quinolizidine

• alkaloid; total synthesis; Findings (−)-Epimyrtine, isolated from Vaccinium myrtillus (Ericaceae) [1][2], is a quinolizidine alkaloid. This alkaloid family exhibits potential pharmacological properties such as anticancer, antibacterial, antiviral and anti-inflammation activities [3][4][5]. This alkaloid

• has been a target of interest for synthetic chemists because of its structural simplicity among the family of quinolizidine structures. Since it has been isolated, numerous total syntheses of this alkaloid in racemic form have been reported in the literature. However, only a few asymmetric syntheses

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• (trans’-7) was obtained in 30% yield. Despite the good yields obtained for these three examples, the cyclisation of 3 under these conditions proved disappointing, with 4,12-trans-8,12-cis-quinolizidine (trans-8) only obtained in 18% yield, along with 40% of monocyclic species 9. In light of the

• effected the desired double reductive amination to give 17 in 30% yield. It is likely that the scope of this sequence could be extended to include indolizidine and quinolizidine scaffolds, and so provide an alternative route to these frameworks, instead of the double Michael addition strategy. The three

• )2 and Sc(OTf)3 and by heating under reflux in toluene, all of which produced varying amounts of 23, with no trace of the bicyclic product detected. This result was disappointing and also, to some degree, surprising given the relative ease of formation of the corresponding quinolizidine compounds. We

Rh-Catalyzed rearrangement of vinylcyclopropane to 1,3-diene units attached to N-heterocycles

• Franca M. Cordero,
• Carolina Vurchio,
• Stefano Cicchi,
• Armin de Meijere and
• Alberto Brandi

Beilstein J. Org. Chem. 2011, 7, 298–303, doi:10.3762/bjoc.7.39

• Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany 10.3762/bjoc.7.39 Abstract Dienes embedded in quinolizidine and indolizidine structures can be prepared in four steps from cyclic nitrones and bicyclopropylidene. The key intermediates α-spirocyclopropanated N-heterocyclic ketones, generated via a

Analogues of amphibian alkaloids: total synthesis of (5R,8S,8aS)-(−)-8-methyl- 5-pentyloctahydroindolizine (8-epi-indolizidine 209B) and [(1S,4R,9aS)-(−)-4-pentyloctahydro- 2H-quinolizin- 1-yl]methanol

• Joseph P. Michael,
• Claudia Accone,
• Charles B. de Koning and
• Christiaan W. van der Westhuyzen

Beilstein J. Org. Chem. 2008, 4, No. 5, doi:10.1186/1860-5397-4-5

• development of enaminones as versatile intermediates for the synthesis of alkaloids and other nitrogen-containing heterocycles. In this paper we describe the enantioselective synthesis of indolizidine and quinolizidine analogues of bicyclic amphibian alkaloids via pyrrolidinylidene- and piperidinylidene

• -containing enaminones. Results Our previously reported synthesis of racemic 8-epi-indolizidine 209B has been extended to the laevorotatory enantiomer, (−)-9. Attempts to adapt the synthetic route in order to obtain quinolizidine analogues revealed that a key piperidinylidene-containing enaminone intermediate

• indolizidine (1-azabicyclo[4.3.0]nonane), quinolizidine (1-azabicyclo[4.4.0]decane) and lehmizidine (1-azabicyclo[5.3.0]decane) classes [1][2]. The first of these classes is by far the most populous, and has commanded enormous attention from organic chemists stimulated by the challenges of designing novel

Combining two-directional synthesis and tandem reactions, part 11: second generation syntheses of (±)-hippodamine and (±)-epi-hippodamine

• Annabella F. Newton,
• Martin Rejzek,
• Marie-Lyne Alcaraz and
• Robert A. Stockman

Beilstein J. Org. Chem. 2008, 4, No. 4, doi:10.1186/1860-5397-4-4

• protecting group. This would render the entire synthesis of hippodamine free of protecting group chemistry – a distinct driving force for a compound which may find use as an agrochemical. Thus we postulated whether we would be able to transform keto-diester 9 into quinolizidine 7 by a tandem reductive

• -Grubbs second generation catalyst in dichloromethane at room temperature for 3 days, giving ketodiester 9 [14]. We tried a range of reductive amination conditions for the formation of quinolizidine 7. The ammonia equivalents tried were ammonium acetate, ammonium chloride and ammonium formate, along with

• further 8 hours, and finally the addition of acetone (to remove any remaining active hydride) and 30 equivalents of acetic acid followed by heating the reaction mixture at reflux for 48 hours gave a clean reaction as monitored by TLC to quinolizidine 7, giving a 74% yield after purification by column

Desymmetrization of 7-azabicycloalkenes by tandem olefin metathesis for the preparation of natural product scaffolds

• Wolfgang Maison,
• Marina Büchert and
• Nina Deppermann

Beilstein J. Org. Chem. 2007, 3, No. 48, doi:10.1186/1860-5397-3-48

• . Background Azabicyclo [x.y.0]alkane scaffolds are ubiquitous structural elements in pharmaceutically important peptide mimetics [1][2][3] and several important classes of natural products such as indolizidine and quinolizidine alkaloids and azasugars. [4][5][6] In consequence, a number of groups have

A convenient allylsilane- N-acyliminium route toward indolizidine and quinolizidine alkaloids

• Roland Remuson

Beilstein J. Org. Chem. 2007, 3, No. 32, doi:10.1186/1860-5397-3-32

• Roland Remuson UMR 6504, CNRS Université Blaise Pascal (Clermont-Fd), 63177 Aubière Cédex, France 10.1186/1860-5397-3-32 Abstract This review relates all the results that we obtained in the field of the total synthesis of indolizidine and quinolizidine alkaloids using a strategy of the addition

• natural alkaloids. Such compounds have been isolated from animals: poison frogs of the family Dendrobatidae have provided a rich source of novel pharmacologically active alkaloids, including a variety of bicyclic nitrogen heterocyclic compounds such as indolizidines. [1][2] Several quinolizidine alkaloids

• alkaloids ideal targets for total synthesis. We have developed a new method to generate bicyclic indolizidine and quinolizidine compounds based on an intramolecular cyclisation of acyliminium ions substituted by an allylsilyl side chain as an internal π-nucleophile (Scheme 1). [6] This reaction has proven

Indolizidines and quinolizidines: natural products and beyond

• Joseph P. Michael

Beilstein J. Org. Chem. 2007, 3, No. 27, doi:10.1186/1860-5397-3-27

• reviews in which their own contributions to the development of indolizidine and quinolizidine chemistry are highlighted. There are articles on the total synthesis of relevant natural products, as well as articles describing novel methodological approaches to the systems of interest. That what may appear

Pd-catalysed [3 + 3] annelations in the stereoselective synthesis of indolizidines

• Olivier Y. Provoost,
• Andrew J. Hazelwood and
• Joseph P. A. Harrity

Beilstein J. Org. Chem. 2007, 3, No. 8, doi:10.1186/1860-5397-3-8

• and have attracted considerable attention because of their varied biological activity (some examples are illustrated in Scheme 1) [1]. Recent studies in our labs have demonstrated that a range of piperidine alkaloids, [2][3][4][5][6] including quinolizidine based targets, [7][8] can be prepared

• cyclisation onto the ester. Previous work in the quinolizidine area had shown that these transformations could be achieved in one-pot by the use of Mg turnings in methanol at ambient temperature [7][8]. Indeed, subjecting 10 to these conditions provided the desired indolizidine 11, albeit in modest yield