Browse
Submit Data
Databases
API
Help

Dataset Information

17 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Thiourea-catalyzed enantioselective iso-Pictet-Spengler reactions.

ABSTRACT: A one-pot condensation of isotryptamines and aldehydes that affords enantiomerically enriched 4-substituted tetrahydro-?-carbolines is reported. The reaction is induced by a chiral thiourea/benzoic acid dual catalyst system. Purification of the N-Boc-protected products by trituration or crystallization provides the optically pure tetrahydro-?-carboline derivatives in a scalable and highly practical procedure.

SUBMITTER: Lee Y

PROVIDER: S-EPMC3206290 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Thiourea-catalyzed enantioselective iso-Pictet-Spengler reactions.

Lee Yunmi Y Klausen Rebekka S RS Jacobsen Eric N EN

Organic letters 20110915 20

A one-pot condensation of isotryptamines and aldehydes that affords enantiomerically enriched 4-substituted tetrahydro-γ-carbolines is reported. The reaction is induced by a chiral thiourea/benzoic acid dual catalyst system. Purification of the N-Boc-protected products by trituration or crystallization provides the optically pure tetrahydro-γ-carboline derivatives in a scalable and highly practical procedure. ...[more]

PMID: 21919478

Similar Datasets

Weak Bronsted acid-thiourea co-catalysis: enantioselective, catalytic protio-Pictet-Spengler reactions.

Project description:The development of one-pot imine formation and asymmetric Pictet-Spengler reactions cocatalyzed by a chiral thiourea and benzoic acid is described. Optically active tetrahydro-beta-carbolines, ubiquitous structural motifs in biologically active natural products, are obtained in high ee directly from tryptamine and aldehyde precursors.

| S-EPMC2664157 | biostudies-literature

Enantioselective Pictet-Spengler Reactions of Isatins for the Synthesis of Spiroindolones.

Project description:The condensation cyclization between isatins and 5-methoxy tryptamine catalyzed by chiral phosphoric acids provides spirooxindole tetrahydro-?-carboline products in excellent yields (up to 99%) and enantioselectivity (up to 98:2 er). A comparison of catalysts provides insight for the substrate scope and factors responsible for efficient catalytic activity and selectivity in the spirocyclization. Chiral phosphoric acids with different 3,3'-substitution on the binaphthyl system and opposite axial chirality afford the spiroindolone product with the same absolute configuration.

| S-EPMC3307811 | biostudies-literature

Catalytic Enantioselective Pictet-Spengler Reaction of α-Ketoamides Catalyzed by a Single H-Bond Donor Organocatalyst.

Project description:The asymmetric Pictet-Spengler reaction (PSR) with aldehydes is well known. However, PSR involving ketones as electrophilic partners is far-less developed. We report herein the first examples of catalytic enantioselective PSR of tryptamines with α-ketoamides. A new class of easily accessible prolyl-urea organocatalysts bearing a single H-bond donor function catalyzes the title reaction to afford 1,1-disubstituted tetrahydro-β-carbolines in excellent yields and enantioselectivities. The kinetic isotope effect using C2-deuterium-labelled tryptamine indicates that the rearomatization of the pentahydro-β-carbolinium ion intermediate might be the rate- and the enantioselectivity-determining step.

| S-EPMC9313548 | biostudies-literature

Mild and efficient cyanuric chloride catalyzed Pictet-Spengler reaction.

Project description:A practical, mild and efficient protocol for the Pictet-Spengler reaction catalyzed by cyanuric chloride (trichloro-1,3,5-triazine, TCT) is described. The 6-endo cyclization of tryptophan/tryptamine and modified Pictet-Spengler substrates with both electron-withdrawing and electron-donating aldehydes was carried out by using a catalytic amount of TCT (10 mol %) in DMSO under a nitrogen atmosphere. TCT catalyzed the Pictet-Spengler reaction involving electron-donating aldehydes in excellent yield. Thus, it has a distinct advantage over the existing methodologies where electron-donating aldehydes failed to undergo 6-endo cyclization. Our methodology provided broad substrate scope and diversity. This is indeed the first report of the use of TCT as a catalyst for the Pictet-Spengler reaction.

| S-EPMC3701375 | biostudies-literature

Enantioselective thiourea-catalyzed cationic polycyclizations.

Project description:A new thiourea catalyst is reported for the enantioselective cationic polycyclization of hydroxylactams. Both the yield and enantioselectivity of this transformation were found to vary strongly with the identity of a single aromatic residue on a common catalyst framework, with more expansive and polarizable arenes proving optimal. Evidence is presented for a mechanism in which stabilizing cation-pi interactions are a principal determinant of enantioselectivity.

| S-EPMC2989498 | biostudies-literature

Chiral Thioureas Promote Enantioselective Pictet-Spengler Cyclization by Stabilizing Every Intermediate and Transition State in the Carboxylic Acid-Catalyzed Reaction.

Project description:An investigation of the mechanism of benzoic acid/thiourea co-catalysis in the asymmetric Pictet-Spengler reaction is reported. Kinetic, computational, and structure-activity relationship studies provide evidence that rearomatization via deprotonation of the pentahydro-?-carbolinium ion intermediate by a chiral thiourea·carboxylate complex is both rate- and enantioselectivity-determining. The thiourea catalyst induces rate acceleration over the background reaction mediated by benzoic acid alone by stabilizing every intermediate and transition state leading up to and including the final selectivity-determining step. Distortion-interaction analyses of the transition structures for deprotonation predicted using density functional theory indicate that differential ?-? and C-H···? interactions within a scaffold organized by multiple hydrogen bonds dictate stereoselectivity. The principles underlying rate acceleration and enantiocontrol described herein are expected to have general implications for the design of selective transformations involving deprotonation of high-energy intermediates.

| S-EPMC5674793 | biostudies-literature

Thiourea-catalyzed enantioselective cyanosilylation of ketones.

Project description:The new chiral amino thiourea catalyst 3d promotes the highly enantioselective cyanosilylation of a wide variety of ketones. The hindered tertiary amine substituent plays a crucial role with regard to both stereoinduction and reactivity, suggesting a cooperative mechanism involving electrophile activation by thiourea and nucleophile activation by the amine.

| S-EPMC3166885 | biostudies-literature

Enantioselective thiourea-catalyzed additions to oxocarbenium ions.

Project description:Asymmetric, catalytic reactions of oxocarbenium ions are reported. Simple, chiral urea and thiourea derivatives are shown to catalyze the enantioselective substitution of silyl ketene acetals onto 1-chloroisochromans. A mechanism involving anion binding by the chiral catalyst to generate a reactive oxocarbenium ion is invoked. Catalysts bearing tertiary benzylic amide groups afforded highest enantioselectivities, with the optimal structure being derived from enantioenriched 2-arylpyrrolidine derivatives.

| S-EPMC2574628 | biostudies-literature

Enantioselective thiourea-catalyzed intramolecular cope-type hydroamination.

Project description:Catalysis of Cope-type rearrangements of bis-homoallylic hydroxylamines is demonstrated using chiral thiourea derivatives. This formal intramolecular hydroamination reaction provides access to highly enantioenriched ?-substituted pyrrolidine products and represents a complementary approach to metal-catalyzed methods.

| S-EPMC3689223 | biostudies-literature

Inverted Binding of Non-natural Substrates in Strictosidine Synthase Leads to a Switch of Stereochemical Outcome in Enzyme-Catalyzed Pictet-Spengler Reactions.

Project description:The Pictet-Spengler reaction is a valuable route to 1,2,3,4-tetrahydro-β-carboline (THBC) and isoquinoline scaffolds found in many important pharmaceuticals. Strictosidine synthase (STR) catalyzes the Pictet-Spengler condensation of tryptamine and the aldehyde secologanin to give (S)-strictosidine as a key intermediate in indole alkaloid biosynthesis. STRs also accept short-chain aliphatic aldehydes to give enantioenriched alkaloid products with up to 99% ee STRs are thus valuable asymmetric organocatalysts for applications in organic synthesis. The STR catalysis of reactions of small aldehydes gives an unexpected switch in stereopreference, leading to formation of the (R)-products. Here we report a rationale for the formation of the (R)-configured products by the STR enzyme from Ophiorrhiza pumila (OpSTR) using a combination of X-ray crystallography, mutational, and molecular dynamics (MD) studies. We discovered that short-chain aldehydes bind in an inverted fashion compared to secologanin leading to the inverted stereopreference for the observed (R)-product in those cases. The study demonstrates that the same catalyst can have two different productive binding modes for one substrate but give different absolute configuration of the products by binding the aldehyde substrate differently. These results will guide future engineering of STRs and related enzymes for biocatalytic applications.

| S-EPMC6966912 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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