Browse
Submit Data
Databases
API
Help

Dataset Information

28 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

5-(Methylthio)tetrazoles as Versatile Synthons in the Stereoselective Synthesis of Polycyclic Pyrazolines via Photoinduced Intramolecular Nitrile Imine-Alkene 1,3-Dipolar Cycloaddition.

ABSTRACT: A key thioether substituent in readily accessible 2-alkyl-5-(methylthio)tetrazoles enables facile photoinduced denitrogenation and intramolecular nitrile imine 1,3-dipolar cycloaddition to afford a wide range of polycyclic pyrazoline products with excellent diastereoselectivity. The methylthio group red-shifts the UV absorbance of the tetrazole, obviating the requirement in all previous substrate systems for at least one aryl substituent, and can subsequently be converted into a variety of other functionalities. This synthetic platform has been applied to the concise total syntheses of the alkaloid natural products (±)-newbouldine and withasomnine.

SUBMITTER: Pla D

PROVIDER: S-EPMC4126266 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

5-(Methylthio)tetrazoles as Versatile Synthons in the Stereoselective Synthesis of Polycyclic Pyrazolines via Photoinduced Intramolecular Nitrile Imine-Alkene 1,3-Dipolar Cycloaddition.

Pla Daniel D Tan Derek S DS Gin David Y DY

Chemical science 20140601 6

A key thioether substituent in readily accessible 2-alkyl-5-(methylthio)tetrazoles enables facile photoinduced denitrogenation and intramolecular nitrile imine 1,3-dipolar cycloaddition to afford a wide range of polycyclic pyrazoline products with excellent diastereoselectivity. The methylthio group red-shifts the UV absorbance of the tetrazole, obviating the requirement in all previous substrate systems for at least one aryl substituent, and can subsequently be converted into a variety of other ...[more]

PMID: 25114776

Similar Datasets

Isoxazolodihydropyridinones: 1,3-dipolar cycloaddition of nitrile oxides onto 2,4-dioxopiperidines.

Project description:Practical and efficient methods have been developed for the diversity-oriented synthesis of isoxazolodihydropyridinones via the 1,3-dipolar cycloaddition of nitrile oxides onto 2,4-dioxopiperidines. A select few of these isoxazolodihydropyridinones were further elaborated with triazoles by copper-catalyzed azide-alkyne cycloaddition reactions. A total of 70 compounds and intermediates were synthesized and analyzed for drug likeness. Sixty-four of these novel compounds were submitted to the NIH Molecular Libraries Small Molecule Repository for high-throughput biological screening.

| S-EPMC3345193 | biostudies-literature

Azirine ligation: fast and selective protein conjugation via photoinduced azirine-alkene cycloaddition.

Project description:We report a new bioorthogonal ligation reaction between p-nitrodiphenylazirine and dimethyl fumarate. This photoinduced azirine-alkene cycloaddition provides a rapid (~2 min) and highly selective route to protein conjugation at neutral pH and room temperature in biological medium.

| S-EPMC2964347 | biostudies-literature

Direct observation of a photoinduced nonstabilized nitrile imine structure in the solid state.

Project description:We report the direct observation of a bent geometry for a nonstabilized nitrile imine in a metal-coordination crystal. The photoinduced tetrazole ring rupture to release N(2) appears to depend on the size of voids around the N(3)-N(4) bond in the crystal lattice. We further observed the selective formation of the 1,3-addition product when a reactive nitrile imine was photogenerated in water. Overall, the bent nitrile imine geometry agrees with the 1,3-dipolar structure, a transient reactive species that mediates the photoinduced 1,3-dipolar cycloaddition in the aqueous medium.

| S-EPMC2797338 | biostudies-literature

Fast alkene functionalization in vivo by Photoclick chemistry: HOMO lifting of nitrile imine dipoles.

Project description:Extremely fast fluorescence labeling (<1 min) of a recombinant alkene-encoded protein in living Escherichia coli cells was observed with tetrazole 1. The electron-donating methoxy substituent raises the energy of the highest occupied molecular orbital of the nitrile-imine intermediate derived from 1. This strategy greatly accelerates the functionalization of alkenes by 1,3-dipolar cycloaddition in living systems.

| S-EPMC2763439 | biostudies-literature

Rapid Metal -free Macromolecular Coupling via in situ Nitrile Oxide-Activated Alkene Cycloaddition.

Project description:Nitrile oxide 1,3 dipolar cycloaddition is a simple and powerful coupling methodology. However, the self-dimerization of nitrile oxides has prevented the widespread use of this strategy for macromolecular coupling. By combining an in situ nitrile oxide generation with a highly reactive activated dipolarophile, we have overcome these obstacles and present a metal-free macromolecular coupling strategy for the modular synthesis of several ABA triblock copolymers. Nitrile oxides were generated in situ from chloroxime terminated poly(dimethylsiloxane) B-blocks and coupled with several distinct hydrophilic (poly(2-methyloxazoline) and poly(ethylene glycol)), and poly(N-isopropylacrylamide) or hydrophobic (poly(L-lactide) A-blocks terminated in activated dipolarophiles in a rapid fashion with high yield. This methodology overcomes many drawbacks of previously reported metal-free methods due to its rapid kinetics, versatility, scalability, and ease of introduction of necessary functionality. Nitrile oxide cycloaddition should find use as an attractive macromolecular coupling strategy for the synthesis of biocompatible polymeric nanostructures.

| S-EPMC4723422 | biostudies-literature

Design and synthesis of laser-activatable tetrazoles for a fast and fluorogenic red-emitting 1,3-dipolar cycloaddition reaction.

Project description:The design and synthesis of a new class of laser light activatable tetrazoles with extended ?-systems is reported. Upon 405 nm laser light irradiation, these bithiophene-substituted tetrazoles underwent extremely fast 1,3-dipolar cycloaddition reactions with dimethyl fumarate with second-order rate constants approaching 4000 M(-1) s(-1). The resulting pyrazoline cycloadducts exhibited solvent-dependent red fluorescence, making these tetrazoles potentially useful as fluorogenic probes for detecting alkenes in vivo.

| S-EPMC3854928 | biostudies-literature

Facile synthesis of stapled, structurally reinforced peptide helices via a photoinduced intramolecular 1,3-dipolar cycloaddition reaction.

Project description:We report the first use of a photoinduced 1,3-dipolar cycloaddition reaction in "stapling" peptide sidechains to reinforce a model peptide helical structure with moderate to excellent yields; the resulting pyrazoline "staplers" exhibit unique fluorescence useful in a cell permeability study.

| S-EPMC2765658 | biostudies-literature

Environmentally Benign Lewis Acid Promoted [2+3]-Dipolar Cycloaddition Reactions of Nitrile Imines with Alkenes in Water.

Project description:Mild and environmentally benign Lewis acid promoted 1,3-dipolar cycloaddition reactions of ?-hydrazonyl chlorides with alkenes in water are reported. These ?-hydrazonyl chlorides, in the presence of Lewis acids, generate nitrile imines in situ which react with dipolarophiles to furnish the corresponding cycloaddition products. In many cases, the required times for the completion of the Lewis acid promoted 1,3-dipolar cycloaddition reactions in water were comparable to the equivalent reactions performed in an organic solvent. Analogous tetrahexylammonium chloride promoted 1,3-dipolar cycloaddition reactions were also performed. The comparison of reaction times and cycloadduct yields for the aforementioned 1,3-dipolar reactions in aqueous and organic media as well as the proposed role of the Lewis acid in the 1,3-dipolar cycloaddition reaction are described.

| S-EPMC3957226 | biostudies-literature

Photoinduced Porcine Gelatin Cross-Linking by Homobi- and Homotrifunctional Tetrazoles.

Project description:Gelatin is a costless polypeptide material of natural origin, able to form hydrogels that are potentially useful in biomaterial scaffold design for drug delivery, cell cultures, and tissue engineering. However, gelatin hydrogels are unstable at physiological conditions, losing their features only after a few minutes at 37 °C. Accordingly, treatments to address this issue are of great interest. In the present work, we propose for the first time the use of bi- and trifunctional tetrazoles, most of them unknown to date, for photoinduced gelatin cross-linking towards the production of physiologically stable hydrogels. Indeed, after UV-B irradiation, aryl tetrazoles generate a nitrilimine intermediate that is reactive towards different functionalities, some of them constitutively present in the amino acid side chains of gelatin. The efficacy of the treatment strictly depends on the structure of the cross-linking agent used, and substantial improved stability was observed by switching from bifunctional to trifunctional cross-linkers.

| S-EPMC8395868 | biostudies-literature

Improved Photoinduced Fluorogenic Alkene-Tetrazole Reaction for Protein Labeling.

Project description:The 1,3-dipolar cycloaddition reaction between an alkene and a tetrazole represents one elegant and rare example of fluorophore-forming bioorthogonal chemistry. This is an attractive reaction for imaging applications in live cells that requires less intensive washing steps and/or needs spatiotemporal resolutions. In the present work, as an effort to improve the fluorogenic property of the alkene-tetrazole reaction, an aromatic alkene (styrene) was investigated as the dipolarophile. Over 30-fold improvement in quantum yield of the reaction product was achieved in aqueous solution. According to our mechanistic studies, the observed improvement is likely due to an insufficient protonation of the styrene-tetrazole reaction product. This finding provides useful guidance to the future design of alkene-tetrazole reactions for biological studies. Fluorogenic protein labeling using the styrene-tetrazole reaction was demonstrated both in vitro and in vivo. This was realized by the genetic incorporation of an unnatural amino acid containing the styrene moiety. It is anticipated that the combination of styrene with different tetrazole derivatives can generally improve and broaden the application of alkene-tetrazole chemistry in real-time imaging in live cells.

| S-EPMC5688003 | 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