Browse
Submit Data
Databases
API
Help

Dataset Information

24 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A concise synthesis of the molecular framework of pleuromutilin.

ABSTRACT: Two syntheses of the tricyclic carbon skeleton of pleuromutilin are reported. Diastereoselective 1,4-conjugate additions were used to elaborate bicyclic precursors at an early stage of each route, while ring-forming olefin metatheses were executed to complete the pleuromutilin carbon framework. The congeners prepared are appropriately functionalized to enable access to diverse pleuromutilin analogues.

SUBMITTER: Liu J

PROVIDER: S-EPMC3156455 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A concise synthesis of the molecular framework of pleuromutilin.

Liu Junjia J Lotesta Stephen D SD Sorensen Erik J EJ

Chemical communications (Cambridge, England) 20101116 5

Two syntheses of the tricyclic carbon skeleton of pleuromutilin are reported. Diastereoselective 1,4-conjugate additions were used to elaborate bicyclic precursors at an early stage of each route, while ring-forming olefin metatheses were executed to complete the pleuromutilin carbon framework. The congeners prepared are appropriately functionalized to enable access to diverse pleuromutilin analogues. ...[more]

PMID: 21079876

Similar Datasets

Total Synthesis of (+)-Pleuromutilin.

Project description:An 18-step synthesis of the antibiotic (+)-pleuromutilin is disclosed. The key steps of the synthesis include a highly stereoselective SmI2-mediated cyclization to establish the eight-membered ring and a stereospecific transannular [1,5]-hydrogen atom transfer to set the C10 stereocenter. This strategy was also used to prepare (+)-12-epi-pleuromutilin. The chemistry described here will enable efforts to prepare new mutilin antibiotics.

| S-EPMC5988231 | biostudies-literature

Total synthesis of structurally diverse pleuromutilin antibiotics.

Project description:The emergence of drug-resistant bacterial pathogens has placed renewed emphasis on the total chemical synthesis of novel antibacterials. Tetracyclines, macrolides, streptogramins and lincosamides are now accessible through flexible and general synthetic routes. Pleuromutilins (antibiotics based on the fungal metabolite pleuromutilin) have remained resistant to this approach, in large part due to the difficulties encountered in the de novo construction of the decahydro-3a,9-propanocyclopenta[8]annulene skeleton. Here we present a platform for the total synthesis of pleuromutilins that provides access to diverse derivatives bearing alterations at previously inaccessible skeletal and peripheral positions. The synthesis is enabled by the serendipitous discovery of a vinylogous Wolff rearrangement, which serves to establish the C9 quaternary centre in the targets, and the development of a highly diastereoselective butynylation of an α-quaternary aldehyde, which forms the C14 secondary alcohol. The versatility of the route is demonstrated through the synthesis of seventeen structurally distinct derivatives, with many possessing potent antibacterial activity.

| S-EPMC9633427 | biostudies-literature

Concise synthesis of capuramycin.

Project description:A concise total synthesis of capuramycin (1), a promising preclinical TB drug lead, is achieved by high-yield formations of the cyanohydrin 5a and 4'',5''-glycal derivative 12. Capuramycin can be synthesized in eight steps from the uridine building block 5a with >30% overall yield. The synthetic intermediates reported here are useful for generation of analogs to improve pharmacokinetic properties of capuramycin.

| S-EPMC4784474 | biostudies-literature

Concise synthesis of (+)-fastigiatine.

Project description:(+)-Fastigiatine was assembled in six steps from (R)-5-methylcyclohex-2-en-1-one. Intermolecular Diels-Alder reaction introduced most of the carbon atoms for the target. The two Boc-protected nitrogen atom building blocks were introduced by a Suzuki coupling and a cuprate addition. A biomimetic transannular Mannich reaction generated the two quaternary centers at a late stage. Each step builds core bonds, and combined with a minimalist protecting group strategy, this approach led to a very concise synthesis.

| S-EPMC5580306 | biostudies-literature

A modular and enantioselective synthesis of the pleuromutilin antibiotics.

Project description:The tricyclic diterpene fungal metabolite (+)-pleuromutilin has served as a starting point for antibiotic development. Semisynthetic modification of its glycolic acid subunit at C14 provided the first analogs fit for human use, and derivatization at C12 led to 12-epi-pleuromutilins with extended-spectrum antibacterial activity, including activity against Gram-negative pathogens. Given the inherent limitations of semisynthesis, however, accessing derivatives of (+)-pleuromutilin with full control over their structure presents an opportunity to develop derivatives with improved antibacterial activities. Here we disclose a modular synthesis of pleuromutilins by the convergent union of an enimide with a bifunctional iodoether. We illustrate our approach through synthesis of (+)-12-epi-mutilin, (+)-11,12-di-epi-mutilin, (+)-12-epi-pleuromutilin, (+)-11,12-di-epi-pleuromutilin, and (+)-pleuromutilin itself in 17 to 20 steps.

| S-EPMC7001679 | biostudies-literature

Concise Synthesis of Broussonone A.

Project description:A concise and expeditious approach to the total synthesis of broussonone A, a p-quinol natural compound, has been developed. The key features of the synthesis include the Grubbs II catalyst mediated cross metathesis of two aromatic subunits, and a chemoselective oxidative dearomatizationin the presence of two phenol moieties. Especially, optimization associated with the CM reaction of ortho-alkoxystyrenes was also studied, which are known to be ineffective for Ru-catalyzed metathesis reactions under conventional reaction conditions because ortho-alkoxy group could coordinate to the ruthenium center, resulting in the potential complication of catalyst inhibition.

| S-EPMC6331890 | biostudies-other

Concise Synthesis of Tetrazole Macrocycle.

Project description:A concise two step synthesis of tetrazole containing macrocycles from readily accessible starting materials is presented. The first step comprises a chemoselective amidation of amino acid derived isocyanocarboxylicacid esters with unprotected symmetrical diamines to afford diverse ?-isocyano-?-amines. In the second step, the ?-isocyano-?-amines undergo an Ugi tetrazole reaction to close the macrocycle. Advantageously, this strategy allows short access to 11-19-membered macrocycles in which substituents can be independently varied at three different positions.

| S-EPMC5633831 | biostudies-literature

A concise synthesis of carolacton.

Project description:A synthesis of carolacton, a myxobacterial natural product that has profound effects on Streptococcus mutans biofilms, is reported. The synthesis proceeds via a longest linear sequence of 14 steps from an Evans ?-ketoimide and enabled preliminary evaluations of the effects of late-stage intermediates on S. mutans biofilms. These studies suggest that further investigations into carolacton's structure-function relationships are warranted.

| S-EPMC3993612 | biostudies-literature

Concise asymmetric synthesis of (-)-bilobalide.

Project description:The Ginkgo biloba metabolite bilobalide is widely ingested by humans but its effect on the mammalian central nervous system is not fully understood1-4. Antagonism of γ-aminobutyric acid A receptors (GABAARs) by bilobalide has been linked to the rescue of cognitive deficits in mouse models of Down syndrome5. A lack of convulsant activity coupled with neuroprotective effects have led some to postulate an alternative, unidentified target4; however, steric congestion and the instability of bilobalide1,2,6 have prevented pull-down of biological targets other than the GABAΑRs. A concise and flexible synthesis of bilobalide would facilitate the development of probes for the identification of potential new targets, analogues with differential selectivity between insect and human GABAΑRs, and stabilized analogues with an enhanced serum half-life7. Here we exploit the unusual reactivity of bilobalide to enable a late-stage deep oxidation that symmetrizes the molecular core and enables oxidation states to be embedded in the starting materials. The same overall strategy may be applicable to G. biloba congeners, including the ginkgolides-some of which are glycine-receptor-selective antagonists8. A chemical synthesis of bilobalide should facilitate the investigation of its biological effects and its therapeutic potential.

| S-EPMC7017908 | biostudies-literature

Concise Synthesis of Functionalized Benzocyclobutenones.

Project description:A concise approach to access functionalized benzocyclobutenones from 3-halophenol derivatives is described. This modified synthesis employs a [2+2] cycloaddition between benzynes generated from dehydrohalogenation of aryl halides using LiTMP and acetaldehyde enolate generated from n-BuLi and THF, followed by oxidation of the benzocyclobutenol intermediates to provide benzocyclobutenones. The [2+2] reaction can be run on a 10-gram scale with an increased yield. A number of functional groups including alkenes and alkynes are tolerated. Coupling of benzynes with ketene silyl acetals to give 8-substituted benzocyclobutenones is also demonstrated.

| S-EPMC4049219 | 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