Browse
Submit Data
Databases
API
Help

Dataset Information

20 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Facile generation of bridged medium-sized polycyclic systems by rhodium-catalysed intramolecular (3+2) dipolar cycloadditions.

ABSTRACT: Bridged medium-sized bicyclo[m.n.2] ring systems are common in natural products and potent pharmaceuticals, and pose a great synthetic challenge. Chemistry for making bicyclo[m.n.2] ring systems remains underdeveloped. Currently, there are no general reactions available for the single-step synthesis of various bridged bicyclo[m.n.2] ring systems from acyclic precursors. Here, we report an unusual type II intramolecular (3+2) dipolar cycloaddition strategy for the syntheses of various bridged bicyclo[m.n.2] ring systems. This rhodium-catalysed cascade reaction provides a relatively general strategy for the direct and efficient regioselective and diastereoselective synthesis of highly functionalized and synthetically challenging bridged medium-sized polycyclic systems. Asymmetric total synthesis of nakafuran-8 was accomplished using this method as a key step. Quantum mechanical calculations demonstrate the mechanism of this transformation and the origins of its multiple selectivities. This reaction will inspire the design of the strategies to make complex bioactive molecules with bridged medium-sized polycyclic systems.

SUBMITTER: Hou BL

PROVIDER: S-EPMC8413281 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Synthesis of Spirobicyclic Pyrazoles by Intramolecular Dipolar Cycloadditions/[1s, 5s] Sigmatropic Rearrangements.

Project description:The formation of fused pyrazoles via intramolecular 1,3-dipolar cycloadditions of diazo intermediates with pendant alkynes is described. A subsequent thermal [1s, 5s] sigmatropic shift of these pyrazole systems resulted in a ring contraction, forming spirocyclic pyrazoles. The limitations of this rearrangement were explored by changing the substituents on the nonmigrating aromatic ring and by using substrates lacking an aromatic linkage to the propargyl group.

| S-EPMC6955098 | biostudies-literature

Asymmetric synthesis of medium-sized rings by intramolecular Au(I)-catalyzed cyclopropanation.

Project description:An efficient method for the asymmetric gold(I)-catalyzed preparation of medium sized rings has been developed. The method provides 7- to 9-membered rings in excellent yield. High enantioselectivities can be achieved for 7- and 8-membered ring products employing chiral gold(I) complexes. The results provide insight into the mechanism, showing the fluxional nature of gold(I)-stabilized vinyl carbenoid intermediates.

| S-EPMC2662771 | biostudies-literature

Sesquiterpene Synthase-Catalysed Formation of a New Medium-Sized Cyclic Terpenoid Ether from Farnesyl Diphosphate Analogues.

Project description:Terpene synthases catalyse the first step in the conversion of prenyl diphosphates to terpenoids. They act as templates for their substrates to generate a reactive conformation, from which a Mg2+ -dependent reaction creates a carbocation-PPi ion pair that undergoes a series of rearrangements and (de)protonations to give the final terpene product. This tight conformational control was exploited for the (R)-germacrene A synthase- and germacradien-4-ol synthase-catalysed formation of a medium-sized cyclic terpenoid ether from substrates containing nucleophilic functional groups. Farnesyl diphosphate analogues with a 10,11-epoxide or an allylic alcohol were efficiently converted to a 11-membered cyclic terpenoid ether that was characterised by HRMS and NMR spectroscopic analyses. Further experiments showed that other sesquiterpene synthases, including aristolochene synthase, δ-cadinene synthase and amorphadiene synthase, yielded this novel terpenoid from the same substrate analogues. This work illustrates the potential of terpene synthases for the efficient generation of structurally and functionally novel medium-sized terpene ethers.

| S-EPMC6334173 | 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

A general strategy for diversifying complex natural products to polycyclic scaffolds with medium-sized rings.

Project description:The interrogation of complex biological pathways demands diverse small molecule tool compounds, which can often lead to important therapeutics for the treatment of human diseases. Since natural products are the most valuable source for the discovery of therapeutics, the derivatization of natural products has been extensively investigated to generate molecules for biological screenings. However, most previous approaches only modified a limited number of functional groups, which resulted in a limited number of skeleta. Here we show a general strategy for the preparation of a library of complex small molecules by combining state-of-the-art chemistry - the site-selective oxidation of C-H bonds - with reactions that expand rigid, small rings in polycyclic steroids to medium-sized rings. This library occupies a unique chemical space compared to selected diverse reference compounds. The diversification strategy developed herein for steroids can also be expanded to other types of natural products.

| S-EPMC6728360 | biostudies-literature

Intramolecular thermal allenyne [2 + 2] cycloadditions; facile construction of the 5-6-4 ring core of sterpurene.

Project description:A variety of 1-allenyl-2-propargyl-substituted cyclopentanol derivatives were found to undergo facile intramolecular microwave-assisted 2+2 alleneyne cycloaddition reactions to generate tricyclic 5-6-4 ring systems present in the sterpurenes.

| S-EPMC2701690 | biostudies-literature

Dynamic Catalytic Highly Enantioselective 1,3-Dipolar Cycloadditions.

Project description:In dynamic covalent chemistry, reactions follow a thermodynamically controlled pathway through equilibria. Reversible covalent-bond formation and breaking in a dynamic process enables the interconversion of products formed under kinetic control to thermodynamically more stable isomers. Notably, enantioselective catalysis of dynamic transformations has not been reported and applied in complex molecule synthesis. We describe the discovery of dynamic covalent enantioselective metal-complex-catalyzed 1,3-dipolar cycloaddition reactions. We have developed a stereodivergent tandem synthesis of structurally and stereochemically complex molecules that generates eight stereocenters with high diastereo- and enantioselectivity through asymmetric reversible bond formation in a dynamic process in two consecutive Ag-catalyzed 1,3-dipolar cycloadditions of azomethine ylides with electron-poor olefins. Time-dependent reversible dynamic covalent-bond formation gives enantiodivergent and diastereodivergent access to structurally complex double cycloadducts with high selectivity from a common set of reagents.

| S-EPMC8456807 | biostudies-literature

Understanding the 1,3-Dipolar Cycloadditions of Allenes.

Project description:We have quantum chemically studied the reactivity, site-, and regioselectivity of the 1,3-dipolar cycloaddition between methyl azide and various allenes, including the archetypal allene propadiene, heteroallenes, and cyclic allenes, by using density functional theory (DFT). The 1,3-dipolar cycloaddition reactivity of linear (hetero)allenes decreases as the number of heteroatoms in the allene increases, and formation of the 1,5-adduct is, in all cases, favored over the 1,4-adduct. Both effects find their origin in the strength of the primary orbital interactions. The cycloaddition reactivity of cyclic allenes was also investigated, and the increased predistortion of allenes, that results upon cyclization, leads to systematically lower activation barriers not due to the expected variations in the strain energy, but instead from the differences in the interaction energy. The geometric predistortion of cyclic allenes enhances the reactivity compared to linear allenes through a unique mechanism that involves a smaller HOMO-LUMO gap, which manifests as more stabilizing orbital interactions.

| S-EPMC7540365 | biostudies-literature

Intramolecular oxyallyl-carbonyl (3 + 2) cycloadditions.

Project description:Cycloadditions involving oxyallyl intermediates typically require an electron-rich diene or alkene, but we have discovered the first examples of the cycloaddition of heteroatom-stabilized oxyallyls onto carbonyl groups. An oxazolidinone-substituted oxyallyl undergoes chemoselective (3 + 2) cycloaddition onto the carbonyl group of a tethered dienone in preference to formation of the expected (4 + 3) cycloadduct. Density functional theory calculations indicated that the (3 + 2) cycloaddition takes place through a concerted, highly asynchronous mechanism. The transition state features simultaneous interactions of the oxyallyl LUMO with the carbonyl ? and lone-pair orbitals, making this reaction "hemipseudopericyclic" (halfway between purely pericyclic and purely pseudopericyclic). Further (3 + 2) cycloadditions involving tethered phenyl ketones and a tethered enone were predicted theoretically and verified experimentally.

| S-EPMC3642281 | biostudies-literature

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions.

Project description:An operationally simple, convenient, and mild strategy for the synthesis of triazole-substituted titanocenes via strain-driven 1,3-dipolar cycloadditions between azide-functionalized titanocenes and cyclooctyne has been developed. It features the first synthesis of titanocenes containing azide groups. These compounds constitute 'second-generation' functionalized titanocene building blocks for further synthetic elaboration. Our synthesis is modular and large numbers of the complexes can in principle be prepared in short periods of time. Some of the triazole-substituted titanocenes display high cyctotoxic activity against BJAB cells. Comparison of the most active complexes allows the identification of structural features essential for biological activity.

| S-EPMC4142980 | 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