regioselective alkylation Dotaz Zobrazit nápovědu
The meta-iodo derivative, fixed in the cone conformation, enables the gram-scale preparation of a meta-bridged calix[4]arene. This intermediate, possessing a fluorene moiety within the macrocyclic skeleton, can be regioselectively alkylated on the corresponding methylene bridge to form a unique substitution pattern in classical calixarene chemistry.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: 6-Bromo-7-[11C]methylpurine ([11C]BMP) is a radiotracer for positron emission tomography (PET) to measure multidrug resistance-associated protein 1 (MRP1) transport activity in different tissues. Previously reported radiosyntheses of [11C]BMP afforded a mixture of 7- and 9-[11C]methyl regioisomers. To prepare for clinical use, we here report an improved regioselective radiosynthesis of [11C]BMP, the results of a non-clinical toxicity study as well as human dosimetry estimates based on mouse PET data. RESULTS: [11C]BMP was synthesised by regioselective N7-methylation of 6-bromo-7H-purine (prepared under good manufacturing practice) with [11C]methyl triflate in presence of 2,2,6,6-tetramethylpiperidine magnesium chloride in a TRACERlab™ FX2 C synthesis module. [11C]BMP was obtained within a total synthesis time of approximately 43 min in a decay-corrected radiochemical yield of 20.5 ± 5.2%, based on starting [11C]methyl iodide, with a radiochemical purity > 99% and a molar activity at end of synthesis of 197 ± 130 GBq/μmol (n = 28). An extended single-dose toxicity study conducted in male and female Wistar rats under good laboratory practice after single intravenous (i.v.) administration of unlabelled BMP (2 mg/kg body weight) revealed no test item related adverse effects. Human dosimetry estimates, based on dynamic whole-body PET data in female C57BL/6J mice, suggested that an i.v. injected activity amount of 400 MBq of [11C]BMP will deliver an effective dose in the typical range of 11C-labelled radiotracers. CONCLUSIONS: [11C]BMP can be produced in sufficient amounts and acceptable quality for clinical use. Data from the non-clinical safety evaluation showed no adverse effects and suggested that the administration of [11C]BMP will be safe and well tolerated in humans.
A new N7 direct regioselective method allowing the introduction of tert-alkyl groups into appropriate 6-substituted purine derivatives is developed. This method is based on a reaction of N-trimethylsilylated purines with a tert-alkyl halide using SnCl4 as a catalyst. In this work, we study the structure and optimal reaction conditions leading to the N7 isomer and in some cases also to the N9 isomer. The main goal is devoted to preparing 7-(tert-butyl)-6-chloropurine as a suitable compound for other purine transformations. The stability of the tert-butyl group at the N7 position is tested for classic model reactions, leading to the preparation of new 6,7-disubstituted purine derivatives, which is also interesting from the point of view of possible biological activity.
- Publikační typ
- časopisecké články MeSH
Monosubstituted derivatives of γ-cyclodextrin (γ-CD) are suitable building blocks for supramolecular polymers, and can also serve as precursors for the synthesis of other regioselectively monosubstituted γ-CD derivatives. We prepared a set of monosubstituted 2I-O-, 3I-O-, and 6I-O-(3-(naphthalen-2-yl)prop-2-en-1-yl) derivatives of γ-CD using two different methods. A key step of the first synthetic procedure is a cross-metathesis between previously described regioisomers of mono-O-allyl derivatives of γ-CD and 2-vinylnaphthalene which gives yields of about 16-25% (2-5% starting from γ-CD). To increase the overall yields, we have developed another method, based on a direct alkylation of γ-CD with 3-(naphthalen-2-yl)allyl chloride as the alkylating reagent. Highly regioselective reaction conditions, which differ for each regioisomer in a used base, gave the monosubstituted isomers in yields between 12-19%. Supramolecular properties of these derivatives were studied by DLS, ITC, NMR, and Cryo-TEM.
- Klíčová slova
- naphthylallyl derivatives, regioselective alkylation, supramolecular properties, synthesis, γ-cyclodextrin,
- Publikační typ
- časopisecké články MeSH
An improved synthetic pathway to the nanobelt-like 1,1,9,9-tetramethyl[9](2,11)teropyrenophane has been developed, and enables the synthesis of gram quantities of material. Key innovations are the development of a sequential chlorination/Friedel-Crafts alkylation reaction, a sequential iodination/Wurtz coupling reaction, and a room-temperature teropyrene-forming reaction. The teropyrenophane was found to form a very stable radical cation and undergo a completely regioselective fourfold bromination reaction.
- Klíčová slova
- EPR spectroscopy, aromaticity, bromination, cyclophanes, structure elucidation,
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The Baeyer-Villiger or Beckmann rearrangements are established methods for the cleavage of ketone derivatives under acidic conditions, proceeding for unsymmetrical precursors selectively at the more substituted site. However, the fragmentation regioselectivity cannot be switched and fragmentation at the less-substituted terminus is so far not possible. We report here that the reaction of ketone enolates with commercial alkyl nitrites provides a direct and regioselective way of fragmenting ketones into esters and oximes or ω-hydroxyimino esters, respectively. A comprehensive study of the scope of this reaction with respect to ketone classes and alkyl nitrites is presented. Control over the site of cleavage is gained through regioselective enolate formation by various bases. Oxidation of kinetic enolates of unsymmetrical ketones leads to the otherwise unavailable "anti-Beckmann" cleavage at the less-substituted side chain, while cleavage of thermodynamic enolates of the same ketones represents an alternative to the Baeyer-Villiger oxidation or the Beckmann rearrangement under basic conditions. The method is suited for the transformation of natural products and enables access to orthogonally reactive dicarbonyl compounds.
- Publikační typ
- časopisecké články MeSH
A general approach towards the synthesis of tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepin-4-one, tetrahydro[1,4]diazepino[1,2-a]indol-1-one and tetrahydro-1H-benzo[4,5]imidazo[1,2-a][1,4]diazepin-1-one derivatives was introduced. A regioselective strategy was developed for synthesizing ethyl 1-(oxiran-2-ylmethyl)-1H-pyrazole-5-carboxylates from easily accessible 3(5)-aryl- or methyl-1H-pyrazole-5(3)-carboxylates. Obtained intermediates were further treated with amines resulting in oxirane ring-opening and direct cyclisation-yielding target pyrazolo[1,5-a][1,4]diazepin-4-ones. A straightforward two-step synthetic approach was applied to expand the current study and successfully functionalize ethyl 1H-indole- and ethyl 1H-benzo[d]imidazole-2-carboxylates. The structures of fused heterocyclic compounds were confirmed by 1H, 13C, and 15N-NMR spectroscopy and HRMS investigation.
- Klíčová slova
- benzimidazole, cyclisation, fused N-heterocycles, indole, oxirane ring-opening, pyrazole, regioselective N-alkylation,
- MeSH
- cyklizace MeSH
- pyrazoly * MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- pyrazoly * MeSH
Chiral indoles annulated on the benzene ring are unique and significant in natural and medicinal compounds. However, accessing these enantioenriched molecules has often been overlooked. The present study introduces an organocatalytic protocol to access these compounds efficiently, demonstrated by substrate scope, functional group tolerance, and using only 1 mol % of a chiral conjugated acid catalyst. Additionally, the study explores regioselectivity, gram-scale reactions, and follow-up transformations, underscoring the method's potential.
- Publikační typ
- časopisecké články MeSH
Regioselective alkylation of γ-cyclodextrin with allyl or propargyl bromide, using optimized reaction conditions, followed by peracetylation of the remaining hydroxyl groups and separation of isomers resulted in the set of peracetylated 2(I)-O-, 3(I)-O- and 6(I)-O-alkylated cyclodextrins in up to 19% yields. Ozonolysis or oxidative cleavage of peracetylated allyl derivatives resulted in a complete set of peracetylated 2(I)-O-, 3(I)-O-, and 6(I)-O-formylmethyl or -carboxymethyl derivatives. All of these derivatives are useful precursors for further preparation of regioselectively monosubstituted derivatives of γ-cyclodextrin.
- MeSH
- alkylace MeSH
- gama-cyklodextriny chemická syntéza chemie MeSH
- magnetická rezonanční spektroskopie MeSH
- molekulární struktura MeSH
- oxidace-redukce MeSH
- pargylin analogy a deriváty chemie MeSH
- stereoizomerie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- gama-cyklodextriny MeSH
- pargylin MeSH
- propargyl bromide MeSH Prohlížeč
Herein, a nickel-catalyzed divergent reductive-Heck reaction of 1-bromo-2-((2-(aryl/alkyl ethynyl)phenoxy)methyl)benzene and 2-(aryl/alkyl ethynyl)phenyl 2-bromobenzenesulfonate derivatives has been demonstrated through the regulation of reducing agents and solvent systems. This scalable protocol offers regio- and stereoselective access to functionalized dibenzo[b,e]oxepine and dibenzo[c,f][1,2]oxathiepine 6,6-dioxide scaffolds in high to excellent yields under a mild set of reaction conditions. This methodology offers a predictable route for the synthesis of medium ring oxygen heterocycles and demonstrates wide substrate scope and outstanding tolerance to various functional groups like hydroxyl and, of course, practical instance via the synthesis of doxepin and nordoxepin molecules. We validate the experimentally proposed reaction mechanism using the density functional theory method. Further, molecular docking interactions were investigated accommodating some of our synthesized molecules.
- Publikační typ
- časopisecké články MeSH
