Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enantioselective synthesis and selective functionalization of 4-aminotetrahydroquinolines as novel GLP-1 secretagogues.

ABSTRACT: Polysubstituted tetrahydroquinolines were obtained in moderate to high yields (28% to 92%) and enantiomeric ratios (er 89:11 to 99:1) by a three-component Povarov reaction using a chiral phosphoric acid catalyst. Significantly, post-Povarov functional group interconversions allowed a rapid access to a library of 36 enantioenriched 4-aminotetrahydroquinoline derivatives featuring five points of diversity. Selected analogs were assayed for their ability to function as glucagon-like peptide-1 (GLP-1) secretagogues.

SUBMITTER: Kazancioglu MZ

PROVIDER: S-EPMC8837726 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Enantioselective synthesis and selective functionalization of 4-aminotetrahydroquinolines as novel GLP-1 secretagogues.

Kazancioglu Mustafa Z MZ Quirion Kevin K Wipf Peter P Skoda Erin M EM

Chirality 20211228 3

Polysubstituted tetrahydroquinolines were obtained in moderate to high yields (28% to 92%) and enantiomeric ratios (er 89:11 to 99:1) by a three-component Povarov reaction using a chiral phosphoric acid catalyst. Significantly, post-Povarov functional group interconversions allowed a rapid access to a library of 36 enantioenriched 4-aminotetrahydroquinoline derivatives featuring five points of diversity. Selected analogs were assayed for their ability to function as glucagon-like peptide-1 (GLP- ...[more]

PMID: 34964164

Similar Datasets

Enantioselective synthesis of (-)-maoecrystal V by enantiodetermining C-H functionalization.

Project description:The evolution of a program directed at the enantioselective total synthesis of maoecrystal V, a highly modified ent-kauranoid, is described. An early stage chiral auxiliary-directed asymmetric C-H functionalization for the construction of a key benzofuran intermediate enabled the first asymmetric synthesis of the natural enantiomer of maoecrystal V, confirming the assigned stereochemistry. A divergent course of the central intramolecular Diels-Alder reaction, which is dependent on the nature of the dienophile, initially led to the development of an unanticipated and previously unknown isomer of maoecrystal V, which we named maoecrystal ZG. In light of the reported selective and potent cytotoxic activity of maoecrystal V, the cytotoxic properties of maoecrystal ZG were also investigated.

| S-EPMC4291805 | biostudies-literature

Enantioselective Synthesis of Isocarbostyril Alkaloids and Analogs Using Catalytic Dearomative Functionalization of Benzene.

Project description:Enantioselective total syntheses of the anticancer isocarbostyril alkaloids (+)-7-deoxypancratistatin, (+)-pancratistatin, (+)-lycoricidine, and (+)-narciclasine are described. Our strategy for accessing this unique class of natural products is based on the development of a Ni-catalyzed dearomative trans-1,2-carboamination of benzene. The effectiveness of this dearomatization approach is notable, as only two additional olefin functionalizations are needed to construct the fully decorated aminocyclitol cores of these alkaloids. Installation of the lactam ring has been achieved through several pathways and a direct interconversion between natural products was established via a late-stage C-7 cupration. Using this synthetic blueprint, we were able to produce natural products on a gram scale and provide tailored analogs with improved activity, solubility, and metabolic stability.

| S-EPMC6488038 | biostudies-literature

Enantioselective Synthesis of Triarylmethanes via Intermolecular C-H Functionalization of Cyclohexadienes with Diaryldiazomethanes.

Project description:Rhodium-catalyzed C-H functionalization of cyclohexadiene derivatives with diaryldiazomethanes followed by oxidation with DDQ provides ready access to triarylmethanes. Two chiral dirhodium tetracarboxylates, Rh2(S-PTAD)4 and Rh2(S-TPPTTL)4, were found to be the optimum chiral catalysts for these transformations. This method showcases the ability of diaryldiazomethanes to perform intermolecular C-H insertion with high enantioselectivity and good yields. The method has a broad substrate scope, leading to triarylmethane products with a variety of aryl and heteroaryl substituents, including benzofuran and pyridine heterocycles.

| S-EPMC10262276 | biostudies-literature

Design of catalysts for site-selective and enantioselective functionalization of non-activated primary C-H bonds.

Project description:C-H functionalization represents a promising approach for the synthesis of complex molecules. Instead of relying on modifying the functional groups present in a molecule, the synthetic sequence is achieved by carrying out selective reactions on the C-H bonds, which traditionally would have been considered to be the unreactive components of a molecule. A major challenge is to design catalysts to control both the site- and stereoselectivity of the C-H functionalization. We have been developing dirhodium catalysts with different selectivity profiles in C-H functionalization reactions with donor/acceptor carbenes as reactive intermediates. Here we describe a new dirhodium catalyst capable of the functionalization of non-activated primary C-H bonds with high levels of site selectivity and enantioselectivity.

| S-EPMC6650386 | biostudies-literature

1,2-Diborylsilanes: Catalytic Enantioselective Synthesis and Site-Selective Cross-Coupling

Project description: Not available

| S-EPMC10927258 | biostudies-literature

Enantioselective Synthesis of Dithia[5]helicenes and their Postsynthetic Functionalization to Access Dithia[9]helicenes.

Project description:A highly enantioselective synthesis of 5,13-disubstituted dibenzo[d,d']benzo[1,2-b:4,3-b']dithiophenes is reported. Key for the successful assembly of these helical architectures is the last two successive Au-catalyzed intramolecular alkyne hydroarylation events. Specifically, the second cyclization is the enantiodetermining step of the whole process and provides the desired helicenes with excellent ee values when a TADDOL-derived 1,2,3-(triazolium)phosphonite moiety (TADDOL: α,α,α',α'-tetraaryl-1,3-dioxolane-4,5-dimethanol) is employed as an ancillary ligand. The absolute stereochemistry of the newly prepared structures has been determined by X-ray crystallography to be P; the optical properties of these heterohelicenes are also reported. A three-step procedure was subsequently developed that allows the transformation of the initially obtained dithia[5]helicenes into dithia[9]helicenes without erosion of the enantiopurity.

| S-EPMC9302117 | biostudies-literature

Enantioselective Synthesis of Spiroindenes by Enol-Directed Rhodium(III)-Catalyzed C-H Functionalization and Spiroannulation.

Project description:Chiral cyclopentadienyl rhodium complexes promote highly enantioselective enol-directed C(sp(2))-H functionalization and oxidative annulation with alkynes to give spiroindenes containing all-carbon quaternary stereocenters. High selectivity between two possible directing groups, as well as control of the direction of rotation in the isomerization of an O-bound rhodium enolate into the C-bound isomer, appear to be critical for high enantiomeric excesses.

| S-EPMC4648053 | biostudies-literature

Synthetic small molecule GLP-1 secretagogues prepared by means of a three-component indole annulation strategy.

Project description:Rational assembly of small molecule libraries for purposes of drug discovery requires an efficient approach in which the synthesis of bioactive compounds is enabled so that numerous structurally related compounds of a similar basic formulation can be derived. Here, we describe (4 + 3) and (3 + 2) indole annulation strategies that quickly generate complex indole heterocycle libraries that contain novel cyclohepta- and cyclopenta[b]indoles, respectively. Screening of one such library comprised of these indoles identifies JWU-A021 to be an especially potent stimulator of glucagon-like peptide-1 (GLP-1) secretion in vitro. Surprisingly, JWU-A021 is also a potent stimulator of Ca(2+) influx through TRPA1 cation channels (EC50 ca. 200 nM), thereby explaining its ability to stimulate GLP-1 release. Of additional importance, the available evidence indicates that JWU-A021 is one of the most potent non-electrophilic TRPA-1 channel agonists yet to be reported in the literature.

| S-EPMC4926213 | biostudies-literature

Catalytic enantioselective synthesis of benzocyclobutenols and cyclobutanols <i>via</i> a sequential reduction/C-H functionalization.

Project description:We report here a sequential enantioselective reduction/C-H functionalization to install contiguous stereogenic carbon centers of benzocyclobutenols and cyclobutanols. This strategy features a practical enantioselective reduction of a ketone and a diastereospecific iridium-catalyzed C-H silylation. Further transformations have been explored, including controllable regioselective ring-opening reactions. In addition, this strategy has been utilized for the synthesis of three natural products, phyllostoxin (proposed structure), grandisol and fragranol.

| S-EPMC8356817 | biostudies-literature

Nickel(II)/Salox-Catalyzed Enantioselective C-H Functionalization.

Project description:Recently, nickel catalysts have garnered considerable attention for their efficacy and versatility in asymmetric catalysis, attributed to their distinctive properties. However, the use of cost-effective and sustainable divalent nickel catalysts in C-H activation/asymmetric alkene insertion poses significant challenges due to the intricate control of stereochemistry in the transformation of the tetracoordinate C-Ni(II) intermediate. Herein, we report a Ni(II)-catalyzed enantioselective C-H/N-H annulation with oxabicyclic alkenes. This protocol offers straightforward access to chiral [2,2,1]-bridged bicyclic compounds bearing four consecutive stereocenters with high enantioselectivity (up to 96% ee). The development of a sterically hindered chiral salicyloxazoline (Salox) ligand, TMS-Salox, is key to the success of this protocol. Mechanistic investigations unveiled that a chiral Ni(III)-metalacyclic intermediate was formed through the in situ oxidation of achiral organometallic Ni(II) species and coordination of the Salox ligand. This process led to the creation of a tailored chiral pocket that guides the approach of alkenes, thereby influencing and determining the stereochemistry.

| S-EPMC11758223 | 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