Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of a Spirocyclic Oxetane-Fused Benzimidazole.

ABSTRACT: A new synthesis of 2-oxa-7-azaspiro[3.5]nonane is described. Spirocyclic oxetanes, including 2-oxa-6-azaspiro[3.3]heptane were converted into o-cycloalkylaminoacetanilides for oxidative cyclizations using Oxone® in formic acid. The expanded spirocyclic oxetane successfully gave the [1,2-a] ring-fused benzimidazole. X-ray crystal structure of the resultant new tetracyclic system, 1',2'-dihydro-4'H-spiro[oxetane-3,3'-pyrido[1,2-a]benzimidazole] and the azetidine ring-opened adduct, N-(2-acetamido-4-bromophenyl)-N-{[3-(chloromethyl) oxetan-3-yl]methyl}acetamide are disclosed.

SUBMITTER: Gurry M

PROVIDER: S-EPMC6332447 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis of a Spirocyclic Oxetane-Fused Benzimidazole.

Gurry Michael M McArdle Patrick P Aldabbagh Fawaz F

Molecules (Basel, Switzerland) 20150730 8

A new synthesis of 2-oxa-7-azaspiro[3.5]nonane is described. Spirocyclic oxetanes, including 2-oxa-6-azaspiro[3.3]heptane were converted into o-cycloalkylaminoacetanilides for oxidative cyclizations using Oxone® in formic acid. The expanded spirocyclic oxetane successfully gave the [1,2-a] ring-fused benzimidazole. X-ray crystal structure of the resultant new tetracyclic system, 1',2'-dihydro-4'H-spiro[oxetane-3,3'-pyrido[1,2-a]benzimidazole] and the azetidine ring-opened adduct, N-(2-acetamido- ...[more]

PMID: 26263961

Similar Datasets

Synthesis of Pyrimidine- and Quinazoline-Fused Benzimidazole-4,7-diones Using Combinatorial Cyclocondensation and Oxidation.

Project description:β-Bromo-α,β-unsaturated aldehydes and 2-bromobenzaldehydes react with 4,7-dimethoxy-1H-benzo[d]imidazole-2-amine by microwave irradiation in dimethylformamide in the presence of a base to give the corresponding dimethoxy-substituted benzo[4,5]imidazo[1,2-a]pyrimidines and benzo[4,5]imidazo[1,2-a]quinazolines, respectively, in moderate to good yields. Oxidation of such N-fused hybrid scaffolds by aqueous ceric ammonium nitrate affords pyrimidine- and quinazoline-fused benzimidazole-4,7-diones in high yields.

| S-EPMC6643376 | biostudies-literature

From Oxetane to Thietane: Extending the Antiviral Spectrum of 2'-Spirocyclic Uridines by Substituting Oxygen with Sulfur.

Project description:In continuation of our efforts of finding novel nucleoside inhibitors for the treatment of viral diseases, we initiated a discovery research program aimed at identifying novel nucleos(t)ide inhibitors for emerging diseases like Dengue and Chikungunya. Based on the previously reported 2'-spiro-oxetane uridine derivatives active against Hepatitis C Virus (HCV), we envisaged its sulfur analogue as an interesting congener both from a synthetic as well as biological point of view. Surprisingly, we found the 2'-spirothietane uridine derivatives not only to be active against HCV and Dengue virus (DENV), viruses belonging to the flavivirus family, but also to demonstrate activity against alphaviruses like Chikungunya virus (CHIKV) and Sindbis virus (SINV).

| S-EPMC9743439 | biostudies-literature

Synthesis, Spectroscopic, X-ray Diffraction and DFT Studies of Novel Benzimidazole Fused-1,4-Oxazepines.

Project description:A series of benzimidazole-tethered oxazepine heterocyclic hybrids has been synthesized in good to excellent yields from an N-alkylated benzimidazole 2-carboxaldehyde, which in turn was accomplished from o-phenylenediamine in three good yielding steps. The calculated molecular structure of compounds 2-methyl-4-(2-((phenylimino)methyl)-1H-benzo-[d]imidazol-1-yl)-butan-2-ol 9 and 10 3,3-dimethyl-N-phenyl-1,2,3,5-tetrahydrobenzo-[4,5]imidazo[2,1-c][1,4]oxazepin-5-amine using the B3LYP/6-31 G(d, p) method were found to agree well with their X-ray structures. The charge distributions at the different atomic sites were computed using the natural bond orbital (NBO) method. The regions of electrophilic and nucleophilic reactivity were shown using a molecular electrostatic potential (MEP) map. In addition, the frontier molecular orbitals of these compounds were discussed at the same level of theory. Nonlinear optical (NLO) properties have also been investigated by computational hyperpolarizability studies, and it was found that Compound 9 is the best candidate for NLO applications.

| S-EPMC6272878 | biostudies-other

Synthesis of N-Fused Benzimidazole-4,7-diones via Sequential Copper-Catalyzed C-N Coupling/Cyclization and Oxidation.

Project description:2-(2-Bromovinyl)- and 2-(2-bromoaryl)-benzimidazoles, including their 4,7-dimethoxy analogs, react with primary amides by microwave irradiation (or usual heating) in dimethylformamide in the presence of a catalytic amount of CuI along with a base to give the corresponding benzo[4,5]imidazo[1,2-c]-pyrimidines and -quinazolines in good yields. Treatment of benzo[4,5]imidazo[1,2-c]-pyrimidines and -quinazolines having methoxy group on benzimidazole moiety with aqueous ceric ammonium nitrate affords unprecedented N-fused hybrid scaffolds, benzo[4,5]imidazo[1,2-c]-pyrimidin-6,9-diones and -quinazoline-8,11-diones, respectively, in high yields.

| S-EPMC6642034 | biostudies-literature

Synthesis of Spirocyclic Piperidines by Radical Hydroarylation.

Project description:Reported here are conditions for the construction of spirocyclic piperidines from linear aryl halide precursors. These conditions employ a strongly reducing organic photoredox catalyst in combination with a trialkylamine reductant to achieve formation of aryl radical species. Regioselective cyclization followed by hydrogen-atom transfer affords a range of complex spiropiperidines. This system operates efficiently under mild conditions without the need for toxic reagents or precious metals.

| S-EPMC8318207 | biostudies-literature

Scalable Synthesis of Biologically Relevant Spirocyclic Pyrrolidines.

Project description:Synthetic approaches toward multigram preparation of spirocyclic α,α-disubstituted pyrrolidines from readily available starting materials are discussed. It was shown that although a number of synthetic methodologies have been known to date, many of the title compounds remain hardly accessible. The most appropriate literature method (which relied on reaction of imines and allyl magnesium halide, followed by bromocyclization) was identified and optimized. It was found that the method is most fruitful for simple non-functionalized substrates. Two novel approaches based on the Sakurai or Petasis reactions of cyclic ketones, followed by hydroboration-oxidation at the allyl moiety thus introduced, were elaborated. The latter method had the largest scope and was beneficial for the substrates containing organosulfur or protected amino functions. For the synthesis of 4-azaspiro[2.4]heptane, an alternative synthetic scheme commencing from tert-butyl cyclopropanecarboxylate (instead of the corresponding ketone) was developed. It was shown that the whole set of the methodologies developed can be used for the synthesis of various spirocyclic α,α-disubstituted pyrrolidines-advanced building blocks of potential importance to medicinal and agrochemistry-at up to a 100 g scale.

| S-EPMC6648774 | biostudies-literature

Stereoselective synthesis of spirocyclic oxindoles via Prins cyclizations.

Project description:The synthesis of spirocyclic oxindole pyran and oxepene frameworks using highly stereoselective Prins cyclizations of homoallylic and bis-homoallylic alcohols and isatin ketals is described.

| S-EPMC2739092 | biostudies-literature

Synthesis and In Vitro Evaluation of Taxol oxetane ring D precursors.

Project description:A series of potential taxoid substrates was prepared in radiolabelled form to probe in vitro for the oxirane formation step and subsequent ring expansion step to the oxetane (ring D) presumably involved in the biosynthesis of the anticancer agent Taxol. None of the taxoid test substrates underwent transformation in cell-free systems from Taxus suggesting that these surrogates bore substitution patterns inappropriate for recognition or catalysis by the target enzymes, or that taxoid oxiranes and oxetanes arise by independent biosynthetic pathways.

| S-EPMC2839165 | biostudies-literature

Synthesis and antiviral properties of spirocyclic [1,2,3]-triazolooxazine nucleosides.

Project description:An efficient synthesis of spirocyclic triazolooxazine nucleosides is described. This was achieved by the conversion of β-D-psicofuranose to the corresponding azido-derivative, followed by alkylation of the primary alcohol with a range of propargyl bromides, obtained by Sonogashira chemistry. The products of these reactions underwent 1,3-dipolar addition smoothly to generate the protected spirocyclic adducts. These were easily deprotected to give the corresponding ribose nucleosides. The library of compounds obtained was investigated for its antiviral activity using MHV (mouse hepatitis virus) as a model wherein derivative 3 f showed the most promising activity and tolerability.

| S-EPMC7162048 | biostudies-literature

New Methods for the Synthesis of Spirocyclic Cephalosporin Analogues.

Project description:Spiro compounds provide attractive targets in drug discovery due to their inherent three-dimensional structures, which enhance protein interactions, aid solubility and facilitate molecular modelling. However, synthetic methodology for the spiro-functionalisation of important classes of penicillin and cephalosporin β-lactam antibiotics is comparatively limited. We report a novel method for the generation of spiro-cephalosporin compounds through a Michael-type addition to the dihydrothiazine ring. Coupling of a range of catechols is achieved under mildly basic conditions (K2CO3, DMF), giving the stereoselective formation of spiro-cephalosporins (d.r. 14:1 to 8:1) in moderate to good yields (28-65%).

| S-EPMC8512572 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data