Synthesis of macrocyclic or linear pyridinium oligomers from 3-substituted pyridines. Model synthetic studies toward macrocyclic marine alkaloids

Gil, Laurent Frédéric; Gateau‐Olesker, Alice; Wong, Yung‐Sing; Chernatova, Lyubov; Marazano, Christian; Das, Bhupesh C.

doi:10.1016/0040-4039(95)00181-b

Cited by 25 publications

(26 citation statements)

References 9 publications

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“…4 3-Alkylpyridinium oligomers mimicking the EGF-active factors, with an oxygen atom in place of a methylene group in the alkyl chain, have been recently synthesized. 9 Some of these studies revealed that the higher the polymerization degree the higher were both biological activity 1,9 and hydrophilicity. 9 Despite the well-defined structure of a single 3-alkylpyridinium unit, little is known about the size of 3-alkylpyridinium polymers (poly-APS) and their possible formation of supramolecular structures in aqueous solutions that might also have an impact on their biological activities.…”

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confidence: 99%

Characterization of Anticholinesterase-Active 3-Alkylpyridinium Polymers from the Marine Sponge Reniera sarai in Aqueous Solutions

et al. 1997

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From the marine sponge Reniera sarai 3-alkylpyridinium oligomers and polymers have been isolated. 3-Alkylpyridinium polymers are potent anticholinesterase agents; in addition, they show hemolytic and cytotoxic activities. Oligomers with a molecular weight lower than 3000 Da do not possess any significant activity. We report structural characterization of 3-alkylpyridinium polymers and their behavior in aqueous solutions. We found that biologically active polymers are composed of head-to-tail 3-alkylpyridinium units. According to MALDI-TOF spectrometry two species of polymers exist, the smaller with a molecular weight of 5520 Da and the larger with a molecular weight of 18 900 Da. Both polymers are soluble only in water, while low molecular oligomers are readily soluble in organic solvents. Polymers form large water-dissolved supramolecular structures with an average hydrodynamic radius of 23 ( 2 nm and, therefore, cannot be separated with size-exclusion chromatography.Recently, several 3-alkylpyridinium compounds endowed with potent biological activities have been isolated from various marine sponges. These compounds have been described as constituted of 3-alkylpyridinium salt subunits (APS). The 3-alkyl chain is bound headto-tail to the nitrogen of the adjacent subunit as in (a) epidermal growth factor (EFG)-active factors, constituted of oligomers built on straight C 8 alkyl chains (1); 1 (b) halitoxin, built on C 8 -C 11 methyl branched alkyl chains (2); 2 (c) cyclostellettamines, composed of straight C 12 -C 15 alkyl chains (3); 3 and (d) amphitoxin, which is composed of oligomeric chains of 3-alkylpyridinium and 3-alkenylpyridinium units (4a, 4b). 4 Related to these compounds are niphatoxins, non-ring oligomers with uncharged pyridine end groups, 5 and haliclamines, trihydropyridine cyclic compounds. 6 These have been proposed as models of biogenic precursors for many complex alkaloids, such as the manzamines 7 and the petrosins, 8 all isolated from marine sponges.The isolated compounds exerted cytotoxicity towards tumor cell lines and hemolysis, 2 inhibition of the epidermal growth factor and toxicity to fish and mice, 1 inhibition of binding of methyl quinuclidinyl benzilate to muscarinic acetylcholine receptors, 3 and strong antifeeding activity. 4 3-Alkylpyridinium oligomers mimicking the EGF-active factors, with an oxygen atom in place of a methylene group in the alkyl chain, have been recently synthesized. 9 Some of these studies revealed that the higher the polymerization degree the higher were both biological activity 1,9 and hydrophilicity. 9Despite the well-defined structure of a single 3-alkylpyridinium unit, little is known about the size of 3-alkylpyridinium polymers (poly-APS) and their possible formation of supramolecular structures in aqueous solutions that might also have an impact on their biological activities. We found that aqueous extracts from the marine sponge Reniera ()Haliclona) sarai Pulitzer-Finali (Haliclonidae) possess strong anticholinesterase and hemolytic activity as well as ...

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confidence: 99%

Characterization of Anticholinesterase-Active 3-Alkylpyridinium Polymers from the Marine Sponge Reniera sarai in Aqueous Solutions

et al. 1997

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“…Previous reports have described the usefulness of Zincke reaction for the preparation of macrocycles and oligomers. [28,29] Our results demonstrate its efficiency for the preparation of porous ionic COPs.…”

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confidence: 62%

Morphological Diversity in Nanoporous Covalent Organic Materials Derived from Viologen and Pyrene

Das¹,

Škorjanc²,

Sharma

et al. 2017

ChemNanoMat

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Adjustment of the morphology of covalent organic nanomaterials is a challenge but can be achieved by perturbing the planarity of the monomers used as core moieties in these polymers. Here we describe a templatefree Zincke reaction for the synthesis of covalent organic nanosheets (CONs) that stack several layers thick and of covalent organic tubes (COTs). Both materials contain the same viologen linker but different pyrene-based cores. Both polymeric materials are nanoporous, cationic, and highly stable in water, even in the presence of acid (1 M HCl) or base (1 M NaOH). Their porosity and ionic surfaces are responsible for high affinities and adsorption capacities for iodine vapor.Porous covalent organic polymers (COPs) are well known for their diverse applications in fields such as gas storage and separation, [1][2][3][4] catalysis, [5][6][7][8] sensing, [9,10] drug delivery, [11] and environmental remediation. [12] In order to design COPs with improved functionality, considerable research has been undertaken to understand the relationship between the morphologies and properties of these materials. [13][14][15] It has been observed that the morphology of COPs can be tuned by changing the symmetry of their constituent building blocks, but precise regulation of COP nanostructure remains a challenging task.Syntheses of covalent organic hollow tubes (COTs) and nanosheets (CONs) are of interest because their large surface areas facilitate the adsorption of small molecule guests. Porous, template-free COPs with uniform tube morphology have been used for device manufacturing [16] and catalysis, [17,18] but reports of the synthesis and application of this type of material remain scarce. Studies of covalent nanosheets are more prevalent, but, this type of material is obtained by either liquid phase exfoliation [19] or mechanical delamination, [20] and these two methods often result in low surface areas because the mechanical forces involved often cause pore blockage. In short, syntheses that rely on mechanical techniques for isolating nanosheets tend to be expensive and non-scalable and produce materials that have limited adsorption efficiency. Designing an efficient and green approach to the large-scale synthesis of porous CONs stacked several (or fewer) layers thick is an open challenge. [21] In general, porous COPs are synthesized from neutral building blocks, which limits the range of application for the materials. For example, neutral COPs are not optimal for the uptake of charged species, including toxic ionic guest molecules. To address this issue, we have begun to develop charged COPs that incorporate redox-active viologens and are capable of adsorbing iodine vapor, toxic dyes, and metal ions by anion exchange. [22,23] Despite their great potential, viologen-based COPs are still rarely documented in the literature, though Li et al. [24] have reported supramolecular organic frameworks (SOFs) that contain viologen struts and form in water.Herein, we report a one-pot, template-free solvothermal synthesis ...

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“…Previous studies [8,12,15] managed to synthesise only oligo-alkylpyridinium salts, but biological screening of some of them indicated that the pore-forming capability was abolished [19]. This highlighted the importance of high degree of polymerisation for this kind of biological activity.…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, the dibromoheptane (6) was coupled with 3-picoline to give the monomer (8). Initially, solutions of monomer in acetonitrile were refluxed to generate small oligomers [12], which was followed by concentration of the materials and subjecting them to microwave irradiation. The size of the polymers was controlled by altering the irradiation time (Fig.…”

Section: Synthesismentioning

confidence: 99%

“…This monomer was then refluxed in dichloromethane to give cyclic dimers and oligomers. Otherwise, refluxing a monomer bearing a terminal chlorine and a linking ether bridge in the alkyl chain, in acetonitrile in the presence of KI for a sustained period, resulted in the production of a mixture of cyclic and linear oligomers with a maximum of 15 monomer units [12]. A rather more sophisticated approach is the formation and subsequent reaction of an N-(2,4-dinitrobenzene) pyridinium salt (Zincke salt) to yield poly-alkylpyridinium salts with up to eight monomer units [15].…”

Section: Introductionmentioning

confidence: 99%

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Chemical synthesis and biological activities of 3-alkyl pyridinium polymeric analogues of marine toxins

et al. 2010

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Two new large poly-1,3-dodecylpyridinium salts, APS12 and APS12-2 of 12.5-and 14.7-kDa size, respectively, were synthesised and tested for their pore-forming and transfection capabilities in HEK 293 and undifferentiated mouse ES cells using patch-clamp recording, Ca 2+ imaging and flow cytometry. Polymerisation reactions were enhanced by microwaves, and the product sizes were controlled by altering the irradiation time. This method can also be applied to obtain polymers with variable linking chains as shown by the preparation of poly-(1,3-octylpyridinium) salt of 11.9-kDa size. Molecular weights of the final products were determined using ESIMS analysis, which also indicated the products to be amongst the largest macro-cycles ever recorded, up to a 900-membered ring. Anti-bacterial, haemolytic and anti-acetylcholinesterase activities were also reported for the two dodecyl pyridinium polymers. These biological activities are characteristic to the structurally related marine toxin, poly-APS.

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Synthesis of macrocyclic or linear pyridinium oligomers from 3-substituted pyridines. Model synthetic studies toward macrocyclic marine alkaloids

Cited by 25 publications

References 9 publications

Characterization of Anticholinesterase-Active 3-Alkylpyridinium Polymers from the Marine Sponge Reniera sarai in Aqueous Solutions

Characterization of Anticholinesterase-Active 3-Alkylpyridinium Polymers from the Marine Sponge Reniera sarai in Aqueous Solutions

Morphological Diversity in Nanoporous Covalent Organic Materials Derived from Viologen and Pyrene

Chemical synthesis and biological activities of 3-alkyl pyridinium polymeric analogues of marine toxins

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