Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Divergent Synthesis and Real-Time Biological Annotation of Optically Active Tetrahydrocyclopenta[c]pyranone Derivatives.

ABSTRACT: Sp³-rich compounds are underrepresented in libraries for probe- and drug-discovery, despite their promise of extending the range of accessible molecular shapes beyond planar geometries. With this in mind, a collection of single-enantiomer bicyclic, fused cyclopentenones underpinned by a complexity-generating Pauson-Khand cyclization was synthesized. A fingerprint of biological actions of these compounds was determined immediately after synthesis using real-time annotation-a process relying on multiplexed measurements of alterations in cell morphological features.

SUBMITTER: Nelson SD

PROVIDER: S-EPMC5171204 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Divergent Synthesis and Real-Time Biological Annotation of Optically Active Tetrahydrocyclopenta[c]pyranone Derivatives.

Nelson Shawn D SD Wawer Mathias J MJ Schreiber Stuart L SL

Organic letters 20161207 24

Sp<sup>3</sup>-rich compounds are underrepresented in libraries for probe- and drug-discovery, despite their promise of extending the range of accessible molecular shapes beyond planar geometries. With this in mind, a collection of single-enantiomer bicyclic, fused cyclopentenones underpinned by a complexity-generating Pauson-Khand cyclization was synthesized. A fingerprint of biological actions of these compounds was determined immediately after synthesis using real-time annotation-a process re ...[more]

PMID: 27978655

Similar Datasets

Real-Time Biological Annotation of Synthetic Compounds.

Project description:Organic chemists are able to synthesize molecules in greater number and chemical complexity than ever before. Yet, a majority of these compounds go untested in biological systems, and those that do are often tested long after the chemist can incorporate the results into synthetic planning. We propose the use of high-dimensional "multiplex" assays, which are capable of measuring thousands of cellular features in one experiment, to annotate rapidly and inexpensively the biological activities of newly synthesized compounds. This readily accessible and inexpensive "real-time" profiling method can be used in a prospective manner to facilitate, for example, the efficient construction of performance-diverse small-molecule libraries that are enriched in bioactives. Here, we demonstrate this concept by synthesizing ten triads of constitutionally isomeric compounds via complexity-generating photochemical and thermal rearrangements and measuring compound-induced changes in cellular morphology via an imaging-based "cell painting" assay. Our results indicate that real-time biological annotation can inform optimization efforts and library syntheses by illuminating trends relating to biological activity that would be difficult to predict if only chemical structure were considered. We anticipate that probe and drug discovery will benefit from the use of optimization efforts and libraries that implement this approach.

| S-EPMC4976700 | biostudies-literature

Synthesis of Thiol Derivatives of Biological Active Compounds for Nanotechnology Application.

Project description:An efficient method of thiol group introduction to the structure of common natural products and synthetic active compounds with recognized biological efficacy such genistein (1), 5,11-dimethyl-5H-indolo[2,3-b]quinolin (2), capecitabine (3), diosgenin (4), tigogenin (5), flumethasone (6), fluticasone propionate (7), ursolic acid methyl ester (8), and β-sitosterol (9) was developed. In most cases, the desired compounds were obtained easily via two-step processes involving esterification reaction employing S-trityl protected thioacetic acid and the corresponding hydoxy-derivative, followed by removal of the trityl-protecting group to obtain the final compounds. The results of our preliminary experiments forced us to change the strategy in the case of genistein (1), and the derivatization of diosgenin (4), tigogenin (5), and capecitabine (3) resulted in obtaining different compounds from those designed. Nevertheless, in all above cases we were able to obtain thiol-containing derivatives of selected biological active compounds. Moreover, a modelling study for the two-step thiolation of genistein and some of its derivatives was accomplished using the density functional theory (B3LP). A hypothesis on a possible reason for the unsuccessful deprotection of the thiolated genistein is also presented based on the semiempirical (PM7) calculations. The developed methodology gives access to new sulphur derivatives, which might find a potential therapeutic benefit.

| S-EPMC7435828 | biostudies-literature

Synthesis, antitumor activity, and mechanism of action of 6-acrylic phenethyl ester-2-pyranone derivatives.

Project description:Based on the scaffolds of caffeic acid phenethyl ester (CAPE) as well as bioactive lactone-containing compounds, 6-acrylic phenethyl ester-2-pyranone derivatives were synthesized and evaluated against five tumor cell lines (HeLa, C6, MCF-7, A549, and HSC-2). Most of the new derivatives exhibited moderate to potent cytotoxic activity. Moreover, HeLa cell lines showed higher sensitivity to these compounds. In particular, compound showed potent cytotoxic activity (IC50 = 0.50-3.45 ?M) against the five cell lines. Further investigation on the mechanism of action showed that induced apoptosis, arrested the cell cycle at G2/M phases in HeLa cells, and inhibited migration through disruption of the actin cytoskeleton. In addition, ADMET properties were also calculated in silico, and compound showed good ADMET properties with good absorption, low hepatotoxicity, and good solubility, and thus, could easily be bound to carrier proteins, without inhibition of CYP2D6. A structure-activity relationship (SAR) analysis indicated that compounds with ortho-substitution on the benzene ring exhibited obviously increased cytotoxic potency. This study indicated that compound is a promising compound as an antitumor agent.

| S-EPMC4390547 | biostudies-literature

Identification of Optically Active Pyrimidine Derivatives as Selective 5-HT2C Modulators.

Project description:A series of pyrimidine derivatives 4a-i were synthesized and evaluated for their binding affinities towards 5-HT2C receptors. With regard to designed molecules 4a-i, the influence of the size of alkyl ether and the absolute configuration of a stereogenic center on the 5-HT2C binding affinity and selectivity was studied. The most promising diasteromeric mixtures 4d and 4e were selected in the initial radioligand binding assay and they were further synthesized as optically active forms starting from optically active alcohols 5d and 5e, prepared by an enzymatic kinetic resolution. Pyrimidine analogue (R,R)-4e displayed an excellent 5-HT2C binding affinity with good selectivity values against a broad range of other 5-HT receptor subtypes.

| S-EPMC6151589 | biostudies-literature

Practical real-time MEG-based neural interfacing with optically pumped magnetometers.

Project description:BackgroundBrain-computer interfaces decode intentions directly from the human brain with the aim to restore lost functionality, control external devices or augment daily experiences. To combine optimal performance with wide applicability, high-quality brain signals should be captured non-invasively. Magnetoencephalography (MEG) is a potent candidate but currently requires costly and confining recording hardware. The recently developed optically pumped magnetometers (OPMs) promise to overcome this limitation, but are currently untested in the context of neural interfacing.ResultsIn this work, we show that OPM-MEG allows robust single-trial analysis which we exploited in a real-time 'mind-spelling' application yielding an average accuracy of 97.7%.ConclusionsThis shows that OPM-MEG can be used to exploit neuro-magnetic brain responses in a practical and flexible manner, and opens up new avenues for a wide range of new neural interface applications in the future.

| S-EPMC8356471 | biostudies-literature

Synthesis of Highly Functionalized 2-Pyranone from Silyl Ketene.

Project description:We report a highly functionalized 2-pyranone small molecule prepared from tert-butyl diphenyl silyl ketene using an alkoxide catalyst and thermally induced rearrangement. Treatment of the silyl ketene with a substoichiometric amount of alkoxide led to the formation of a trimer which was isolated and fully characterized; heating this trimer in a 1,4-dioxane solution induced a thermal rearrangement, yielding the product 2-pyranone. The isolated intermediate and product are characterized by 1D and 2D nuclear magnetic resonance (NMR) spectroscopies, mass spectrometry, and single crystal X-ray diffraction. A mechanism for the thermally induced rearrangement is proposed based on 1H NMR studies, and a rate law is derived from the proposed mechanism with steady-state approximation. This work illustrates a route for the formation of highly functionalized and modifiable 2-pyranone motifs with potential biological activity. The formation of the trimer, and thus the functionalized 2-pyranone, is highly dependent on the silyl substituents and alkoxide counterion and thus indicates the intriguing reactivity of highly functionalized small molecules.

| S-EPMC6645212 | biostudies-literature

Real-time divergent evolution in plants driven by pollinators.

Project description:Pollinator-driven diversification is thought to be a major source of floral variation in plants. Our knowledge of this process is, however, limited to indirect assessments of evolutionary changes. Here, we employ experimental evolution with fast cycling Brassica rapa plants to demonstrate adaptive evolution driven by different pollinators. Our study shows pollinator-driven divergent selection as well as divergent evolution in plant traits. Plants pollinated by bumblebees evolved taller size and more fragrant flowers with increased ultraviolet reflection. Bumblebees preferred bumblebee-pollinated plants over hoverfly-pollinated plants at the end of the experiment, showing that plants had adapted to the bumblebees' preferences. Plants with hoverfly pollination became shorter, had reduced emission of some floral volatiles, but increased fitness through augmented autonomous self-pollination. Our study demonstrates that changes in pollinator communities can have rapid consequences on the evolution of plant traits and mating system.

| S-EPMC5424062 | biostudies-literature

Stereospecific synthesis of silicon-stereogenic optically active silylboranes and general synthesis of chiral silyl Anions.

Project description:Silicon-stereogenic optically active silylboranes could potentially allow the formation of chiral silyl nucleophiles as well as the synthesis of various chiral silicon compounds. However, the synthesis of such silicon-stereogenic silylboranes has not been achieved so far. Here, we report the synthesis of silicon-stereogenic optically active silylboranes via a stereospecific Pt(PPh3)4-catalyzed Si-H borylation of chiral hydrosilanes, which are synthesized by stoichiometric and catalytic asymmetric synthesis, in high yield and very high or perfect enantiospecificity (99% es in one case, and >99% es in the others) with retention of the configuration. Furthermore, we report a practical approach to generate silicon-stereogenic silyl nucleophiles with high enantiopurity and configurational stability using MeLi activation. This protocol is suitable for the stereospecific and general synthesis of silicon-stereogenic trialkyl-, dialkylbenzyl-, dialkylaryl-, diarylalkyl-, and alkylary benzyloxy-substituted silylboranes and their corresponding silyl nucleophiles with excellent enantiospecificity (>99% es except one case of 99% es). Transition-metal-catalyzed C-Si bond-forming cross-coupling reactions and conjugate-addition reactions are also demonstrated. The mechanisms underlying the stability and reactivity of such chiral silyl anion were investigated by combining NMR spectroscopy and DFT calculations.

| S-EPMC10492825 | biostudies-literature

Enantioselective Tail-to-Head Terpene Cyclizations by Optically Active Hexameric Resorcin[4]arene Capsule Derivatives.

Project description:Molecular capsules enable the conversion of substrates inside a closed cavity, mimicking to some extent enzymatic catalysis. Chirality transfer from the molecular capsule onto the encapsulated substrate has been only studied in a few cases. Here we demonstrate that chirality transfer is possible inside a rather large molecular container of approximately 1400 Å3 . Specifically, we present 1) the first examples of optically active hexameric resorcin[4]arene capsules, 2) their ability to enantioselectively catalyze tail-to-head terpene cyclizations, and 3) the surprisingly high sensitivity of enantioselectivity on the structural modifications.

| S-EPMC9323437 | biostudies-literature

Configurational Molecular Glue: One Optically Active Polymer Attracts Two Oppositely Configured Optically Active Polymers.

Project description:D-configured poly(D-lactic acid) (D-PLA) and poly(D-2-hydroxy-3-methylbutanoic acid) (D-P2H3MB) crystallized separately into their homo-crystallites when crystallized by precipitation or solvent evaporation, whereas incorporation of L-configured poly(L-2-hydroxybutanoic acid) (L-P2HB) in D-configured D-PLA and D-P2H3MB induced co-crystallization or ternary stereocomplex formation between D-configured D-PLA and D-P2H3MB and L-configured L-P2HB. However, incorporation of D-configured poly(D-2-hydroxybutanoic acid) (D-P2HB) in D-configured D-PLA and D-P2H3MB did not cause co-crystallization between D-configured D-PLA and D-P2H3MB and D-configured D-P2HB but separate crystallization of each polymer occurred. These findings strongly suggest that an optically active polymer (L-configured or D-configured polymer) like unsubstituted or substituted optically active poly(lactic acid)s can act as "a configurational or helical molecular glue" for two oppositely configured optically active polymers (two D-configured polymers or two L-configured polymers) to allow their co-crystallization. The increased degree of freedom in polymer combination is expected to assist to pave the way for designing polymeric composites having a wide variety of physical properties, biodegradation rate and behavior in the case of biodegradable polymers.

| S-EPMC5364539 | 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