Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Creation and manipulation of common functional groups en route to a skeletally diverse chemical library.

ABSTRACT: We have developed an efficient strategy to a skeletally diverse chemical library, which entailed a sequence of enyne cycloisomerization, [4 + 2] cycloaddition, alkene dihydroxylation, and diol carbamylation. Using this approach, only 16 readily available building blocks were needed to produce a representative 191-member library, which displayed broad distribution of molecular shapes and excellent physicochemical properties. This library further enabled identification of a small molecule, which effectively suppressed glycolytic production of ATP and lactate in CHO-K1 cell line, representing a potential lead for the development of a new class of glycolytic inhibitors.

SUBMITTER: Cui J

PROVIDER: S-EPMC3084086 | biostudies-other | 2011 Apr

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Creation and manipulation of common functional groups en route to a skeletally diverse chemical library.

Cui Jiayue J Hao Jason J Ulanovskaya Olesya A OA Dundas Joseph J Liang Jie J Kozmin Sergey A SA

Proceedings of the National Academy of Sciences of the United States of America 20110307 17

We have developed an efficient strategy to a skeletally diverse chemical library, which entailed a sequence of enyne cycloisomerization, [4 + 2] cycloaddition, alkene dihydroxylation, and diol carbamylation. Using this approach, only 16 readily available building blocks were needed to produce a representative 191-member library, which displayed broad distribution of molecular shapes and excellent physicochemical properties. This library further enabled identification of a small molecule, which e ...[more]

PMID: 21383124

Similar Datasets

Emulating the logic of monoterpenoid alkaloid biogenesis to access a skeletally diverse chemical library.

Project description:We have developed a synthetic strategy that mimics the diversity-generating power of monoterpenoid indole alkaloid biosynthesis. Our general approach goes beyond diversification of a single natural product-like substructure and enables production of a highly diverse collection of small molecules. The reaction sequence begins with rapid and highly modular assembly of the tetracyclic indoloquinolizidine core, which can be chemoselectively processed into several additional skeletally diverse structural frameworks. The general utility of this approach was demonstrated by parallel synthesis of two representative chemical libraries containing 847 compounds with favorable physicochemical properties to enable its subsequent broad pharmacological evaluation.

| S-EPMC3842850 | biostudies-literature

Synthesis of skeletally diverse and stereochemically complex library templates derived from isosteviol and steviol.

Project description:We have applied a diversity-oriented approach for the synthesis of skeletally diverse and stereochemically complex templates for small-molecule library production by performing Beckmann rearrangement and Beckmann fragmentation reactions on the bicyclo[3.2.1]octane rings of steviol and isosteviol, aglycones derived from the diterpene natural product stevioside. The optimization of these two reaction pathways is presented along with the successful application of a photo-Beckmann rearrangement. This work also led to the discovery of cyano-Prins-type and Thorpe-Ziegler-type cyclization reactions.

| S-EPMC3638842 | biostudies-literature

Antiferromagnetic Skyrmion: Stability, Creation and Manipulation.

Project description:Magnetic skyrmions are particle-like topological excitations in ferromagnets, which have the topo-logical number Q?=?±?1, and hence show the skyrmion Hall effect (SkHE) due to the Magnus force effect originating from the topology. Here, we propose the counterpart of the magnetic skyrmion in the antiferromagnetic (AFM) system, that is, the AFM skyrmion, which is topologically protected but without showing the SkHE. Two approaches for creating the AFM skyrmion have been described based on micromagnetic lattice simulations: (i) by injecting a vertical spin-polarized current to a nanodisk with the AFM ground state; (ii) by converting an AFM domain-wall pair in a nanowire junction. It is demonstrated that the AFM skyrmion, driven by the spin-polarized current, can move straightly over long distance, benefiting from the absence of the SkHE. Our results will open a new strategy on designing the novel spintronic devices based on AFM materials.

| S-EPMC4838875 | biostudies-other

Facile and unified approach to skeletally diverse, privileged scaffolds.

Project description:A novel strategy has been developed to generate a diverse array of privileged scaffolds from readily available tetrahydropyridine precursors that may be prepared by a multicomponent assembly process followed by a ring-closing metathesis. The functionality embedded in these key intermediates enables their facile elaboration into more complex structures of biological relevance by a variety of ring-forming processes and refunctionalizations.

| S-EPMC3094476 | biostudies-literature

Synthetic, Mechanistic, and Biological Interrogation of <i>Ginkgo biloba</i> Chemical Space En Route to (-)-Bilobalide.

Project description:Here we interrogate the structurally dense (1.64 mcbits/Å3) GABAA receptor antagonist bilobalide, intermediates en route to its synthesis, and related mechanistic questions. 13C isotope labeling identifies an unexpected bromine migration en route to an α-selective, catalytic asymmetric Reformatsky reaction, ruling out an asymmetric allylation pathway. Experiment and computation converge on the driving forces behind two surprising observations. First, an oxetane acetal persists in concentrated mineral acid (1.5 M DCl in THF-d8/D2O); its longevity is correlated to destabilizing steric clash between substituents upon ring-opening. Second, a regioselective oxidation of des-hydroxybilobalide is found to rely on lactone acidification through lone-pair delocalization, which leads to extremely rapid intermolecular enolate equilibration. We also establish equivalent effects of (-)-bilobalide and the nonconvulsive sesquiterpene (-)-jiadifenolide on action potential-independent inhibitory currents at GABAergic synapses, using (+)-bilobalide as a negative control. The high information density of bilobalide distinguishes it from other scaffolds and may characterize natural product (NP) space more generally. Therefore, we also include a Python script to quickly (ca. 132 000 molecules/min) calculate information content (Böttcher scores), which may prove helpful to identify important features of NP space.

| S-EPMC7727090 | biostudies-literature

Skeletally diverse small molecules using a build/couple/pair strategy.

Project description:Intermolecular couplings of simple building blocks using catalytic, stereoselective cross-Mannich reactions followed by intramolecular functional group-pairing reactions of easily accessed variants of the Mannich products are explored as a route to skeletally diverse small molecules. The synthetic pathway yields products having 12 different skeletons using only three steps and has the potential to enable substantial stereochemical diversification in the future.

| S-EPMC2661762 | biostudies-literature

Prion protein: evolution caught en route.

Project description:The prion protein displays a unique structural ambiguity in that it can adopt multiple stable conformations under physiological conditions. In our view, this puzzling feature resulted from a sudden environmental change in evolution when the prion, previously an integral membrane protein, got expelled into the extracellular space. Analysis of known vertebrate prions unveils a primordial transmembrane protein encrypted in their sequence, underlying this relocalization hypothesis. Apparently, the time elapsed since this event was insufficient to create a "minimally frustrated" sequence in the new milieu, probably due to the functional constraints set by the importance of the very flexibility that was created in the relocalization. This scenario may explain why, in a structural sense, the prion protein is still en route toward becoming a foldable globular protein.

| S-EPMC31852 | biostudies-literature

Biosynthesizing structurally diverse diols via a general route combining oxidative and reductive formations of OH-groups.

Project description:Diols encompass important bulk and fine chemicals for the chemical, pharmaceutical and cosmetic industries. During the past decades, biological production of C3-C5 diols from renewable feedstocks has received great interest. Here, we elaborate a general principle for effectively synthesizing structurally diverse diols by expanding amino acid metabolism. Specifically, we propose to combine oxidative and reductive formations of hydroxyl groups from amino acids in a thermodynamically favorable order of four reactions catalyzed by amino acid hydroxylase, L-amino acid deaminase, α-keto acid decarboxylase and aldehyde reductase consecutively. The oxidative formation of hydroxyl group from an alkyl group is energetically more attractive than the reductive pathway, which is exclusively used in the synthetic pathways of diols reported so far. We demonstrate this general route for microbial production of branched-chain diols in E. coli. Ten C3-C5 diols are synthesized. Six of them, namely isopentyldiol (IPDO), 2-methyl-1,3-butanediol (2-M-1,3-BDO), 2-methyl-1,4-butanediol (2-M-1,4-BDO), 2-methyl-1,3-propanediol (MPO), 2-ethyl-1,3-propanediol (2-E-1,3-PDO), 1,4-pentanediol (1,4-PTD), have not been biologically synthesized before. This work opens up opportunities for synthesizing structurally diverse diols and triols, especially by genome mining, rational design or directed evolution of proper enzymes.

| S-EPMC8948231 | biostudies-literature

Prephenate decarboxylases: a new prephenate-utilizing enzyme family that performs nonaromatizing decarboxylation en route to diverse secondary metabolites.

Project description:Prephenate is the direct precursor of phenylpyruvate and 4-hydroxyphenylpyruvate in the biogenesis of phenylalanine and tyrosine by action of the decarboxylative, aromatizing enzymes prephenate dehydratase and dehydrogenase, respectively. The recent characterization of BacA in bacilysin biosynthesis as a nonaromatizing decarboxylase reveals a new route from prephenate in the biosynthesis of nonproteinogenic amino acids. This study describes two additional enzymes, AerD from Planktothrix agardhii and SalX from Salinispora tropica, that utilize the central building block prephenate for flux down distinct pathways to amino acid products, representing a new metabolic fate for prephenate and establishing a new family of nonaromatizing prephenate decarboxylases.

| S-EPMC2957524 | biostudies-literature

Synthesis of a Diverse Library of N,N-Dimethylamino Containing Monomers Appropriate as Lipid Head Groups.

Project description:We report on the synthesis of a diverse library of N,N-dimethylamino containing monomers. Subjecting these monomers to Chabrier reaction conditions would yield lipids with polymerizable head groups. This library of lipid head groups is equipped with a variety of arm lengths containing reduction-oxidation polymerizable groups at the terminus.

| S-EPMC3180924 | 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