Browse
Submit Data
Databases
API
Help

Dataset Information

44 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Access to Indole-Annulated Medium-Sized Lactams through Protonation/Deuteration-Induced Ring-Opening of Spiroindolines.

ABSTRACT: A protocol has been developed to access indole-annulated eight- and nine-membered lactams through protonation-induced ring-opening of spiroindolines, which are dearomative Heck products of tetrahydro-β-carbolines or hexahydroazepino[3,4-b]indoles. Brønsted acids and nucleophiles were explored and compared in the transformation. A combination of deuterated hydrochloride and deuterated methanol enables deuterative ring-opening of spiroindolines to afford medium-sized lactam diastereoisomers with a deuterium content ratio around 1:1.

SUBMITTER: Qiao J

PROVIDER: S-EPMC8482774 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Access to Indole-Annulated Medium-Sized Lactams through Protonation/Deuteration-Induced Ring-Opening of Spiroindolines.

Qiao Jianhui J Liu Huili H Wang Shaozhong S

ACS omega 20210914 38

A protocol has been developed to access indole-annulated eight- and nine-membered lactams through protonation-induced ring-opening of spiroindolines, which are dearomative Heck products of tetrahydro-β-carbolines or hexahydroazepino[3,4-<i>b</i>]indoles. Brønsted acids and nucleophiles were explored and compared in the transformation. A combination of deuterated hydrochloride and deuterated methanol enables deuterative ring-opening of spiroindolines to afford medium-sized lactam diastereoisomers ...[more]

PMID: 34604684

Similar Datasets

Antimalarial Dibenzannulated Medium-Ring Keto Lactams.

Project description:We discovered dibenzannulated medium-ring keto lactams (11,12-dihydro-5H-dibenzo[b,g]azonine-6,13-diones) as a new antimalarial chemotype. Most of these had chromatographic LogD7.4 values ranging from <0 to 3 and good kinetic solubilities (12.5 to >100 μg/mL at pH 6.5). The more polar compounds in the series (LogD7.4 values of <2) had the best metabolic stability (CLint values of <50 μL/min/mg protein in human liver microsomes). Most of the compounds had relatively low cytotoxicity, with IC50 values >30 μM, and there was no correlation between antiplasmodial activity and cytotoxicity. The four most potent compounds had Plasmodium falciparum IC50 values of 4.2 to 9.4 nM and in vitro selectivity indices of 670 to >12,000. They were more than 4 orders-of-magnitude less potent against three other protozoal pathogens (Trypanosoma brucei rhodesiense, Trypanosoma cruzi, and Leishmania donovani) but did have relatively high potency against Toxoplasma gondii, with IC50 values ranging from 80 to 200 nM. These keto lactams are converted into their poorly soluble 4(1H)-quinolone transannular condensation products in vitro in culture medium and in vivo in mouse blood. The similar antiplasmodial potencies of three keto lactam-quinolone pairs suggest that the quinolones likely contribute to the antimalarial activity of the lactams.

| S-EPMC10860121 | biostudies-literature

Synthesis of Benzannulated Medium-ring Lactams via a Tandem Oxidative Dearomatization-Ring Expansion Reaction.

Project description:Medium-ring natural products exhibit diverse biological activities but such scaffolds are underrepresented in probe and drug discovery efforts due to the limitations of classical macrocyclization reactions. We report herein a tandem oxidative dearomatization-ring-expanding rearomatization (ODRE) reaction that generates benzannulated medium-ring lactams directly from simple bicyclic substrates. The reaction accommodates diverse aryl substrates (haloarenes, aryl ethers, aryl amides, heterocycles) and strategic incorporation of a bridgehead alcohol generates a versatile ketone moiety in the products amenable to downstream modifications. Cheminformatic analysis indicates that these medium rings access regions of chemical space that overlap with related natural products and are distinct from synthetic drugs, setting the stage for their use in discovery screening against novel biological targets.

| S-EPMC6242278 | biostudies-literature

A ring fragmentation approach to medium-sized cyclic 2-alkynones.

Project description:Bicyclic γ-silyloxy-β-hydroxy-α-diazoketones, in which the Cβ-Cγ bond is the ring fusion bond, productively fragment when treated with tin(IV) chloride to provide medium-sized cyclic 2-alkynones. This method provides good to excellent yields of 10-, 11-, and 12-membered alkynone products.

| S-EPMC3253231 | biostudies-literature

Protonation of P-Stereogenic Phosphiranes: Phospholane Formation via Ring Opening and C-H Activation.

Project description:Protonation of cyclopropanes and aziridines is well-studied, but reactions of phosphiranes with acids are rare and have not been reported to result in ring opening. Treatment of syn-Mes*PCH2CHR (Mes* = 2,4,6-(t-Bu)3C6H2, R = Me or Ph, syn-1-2) or anti-Mes*PCH2CHPh (anti-2) with triflic acid resulted in regiospecific anti-Markovnikov C-protonation with ring opening and cyclophosphination of a Mes* ortho-t-Bu group to yield the phospholanium cations [PH(CH2CH2R)(4,6-(t-Bu)2-2-CMe2CH2C6H2)][OTf] (R = Me or Ph, 3-4), which were deprotonated with NEt3 to give phospholanes 5-6. Enantioenriched or racemic syn-1 both gave racemic 3. The byproduct [Mes*PH(CH2CH2Me)(OH)][OTf] (7) was formed from syn-1 and HOTf in the presence of water. Density functional theory calculations suggested that P-protonation followed by ring opening and hydride migration to C yields the phosphenium ion, [Mes*P(CH2CH2Me)][OTf], which undergoes C-H oxidative addition of an o-t-Bu methyl group. This work established a new reactivity pattern for phosphiranes.

| S-EPMC10077540 | biostudies-literature

Synthesis of Indole Derivatives via Aryl Triazole Ring-Opening and Subsequent Cyclization.

Project description:A metal-free two-step synthetic approach for obtaining indole derivatives from aryl triazole fragment-containing compounds has been developed. In the first step, the Dimroth equilibrium, followed by nitrogen extrusion, Wolff rearrangement, and amine nucleophile addition, leads to the formation of N-aryl ethene-1,1-diamines. In the second step, the latter intermediates are cyclized into the target 1H-indoles in the presence of iodine. The developed method ensures the synthesis of indoles that possess N-substituents at the indole C2 position. Depending on the applied N-nucleophile, the indolization step provides a selectivity either towards 1H-indoles or 1-aryl-1H-indoles.

| S-EPMC11767399 | biostudies-literature

Synthesis of medium-ring lactams and macrocyclic peptide mimetics <i>via</i> conjugate addition/ring expansion cascade reactions.

Project description:A novel conjugate addition/ring expansion (CARE) cascade reaction sequence is reported that enables medium-sized ring and macrocyclic bis-lactams to be prepared from primary amines and cyclic imides. The reactions are simple to perform, generally high yielding, and very broad in scope, especially with respect to the primary amine component. CARE reactions can also be performed iteratively, enabling β-peptoid-based macrocyclic peptide mimetics to be 'grown' via well controlled, sequential 4-atom ring expansion reactions, with the incorporation of varied functionalised amines during each iteration.

| S-EPMC8905531 | biostudies-literature

Synthesis of a stereochemically diverse library of medium-sized lactams and sultams via S(N)Ar cycloetherification.

Project description:We have implemented an aldol-based "build/couple/pair" (B/C/P) strategy for the synthesis of stereochemically diverse 8-membered lactam and sultam scaffolds via S(N)Ar cycloetherification. Each scaffold contains two handles, an amine and aryl bromide, for solid-phase diversification via N-capping and Pd-mediated cross coupling. A sparse matrix design strategy that achieves the dual objective of controlling physicochemical properties and selecting diverse library members was implemented. The production of two 8000-membered libraries is discussed including a full analysis of library purity and property distribution. Library diversity was evaluated in comparison to the Molecular Library Small Molecule Repository (MLSMR) through the use of a multifusion similarity (MFS) map and principal component analysis (PCA).

| S-EPMC3134123 | biostudies-literature

Thionium ion initiated medium-sized ring formation: the total synthesis of asteriscunolide D.

Project description:The first synthesis of the biologically active humulene natural product asteriscunolide D has been accomplished in nine steps without the use of protecting groups. The challenging 11-membered ring was forged via a diastereoselective thionium ion initiated cyclization, which constitutes a formal aldol disconnection to form a strained macrocycle. A stereospecific thioether activation-elimination protocol was developed for selective E-olefin formation, thus providing access to the most biologically active asteriscunolide. The absolute stereochemical configuration was established by the Zn-ProPhenol catalyzed enantioselective addition of methyl propiolate to an aliphatic aldehyde to afford a γ-hydroxy propiolate as a handle for butenolide formation via Ru-catalyzed alkene-alkyne coupling.

| S-EPMC3268366 | biostudies-literature

Cobalt(III)-catalyzed asymmetric ring-opening of 7-oxabenzonorbornadienes via indole C-H functionalization.

Project description:Asymmetric ring-opening of 7-oxabenzonorbornadienes is achieved via Co-catalyzed indole C-H functionalization. The utilization of chiral Co-catalyst consisting of a binaphthyl-derived trisubstituted cyclopentadienyl ligand resulted in high yields (up to 99%) and excellent enantioselectivity (>99% ee) for the target products with tolerance for diverse functional groups. Opposite diastereoselectivities are obtained with chiral Co-catalyst or Cp*CoI2CO. Combined experimental and computational studies suggest β-oxygen elimination being the selectivity-determining step of the reaction. Meanwhile, the reactions of 7-azabenzonorbornadiene could also be executed in a diastereodivergent manner.

| S-EPMC9968317 | biostudies-literature

Conversion of Medium-Sized Lactams to α-Vinyl or α-Acetylenyl Azacycles via N,O-Acetal TMS Ethers.

Project description:α-Vinyl or α-acetylenyl azacycles were easily synthesized from 7- to 9-membered lactams and 6- to 9-membered lactams via N,O-acetal trimethylsilyl (TMS) ethers. Organocopper and organostannane reagents afforded reasonable yields for the respective N-acyliminium ion vinylation and acetylenylation intermediates generated from N,O-acetal TMS ethers in the presence of a Lewis acid.

| S-EPMC6278647 | 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