Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Enantioselective reduction of sulfur-containing cyclic imines through biocatalysis.

ABSTRACT: The 3-thiazolidine ring represents an important structural motif in life sciences molecules. However, up to now reduction of 3-thiazolines as an attractive approach failed by means of nearly all chemical reduction technologies for imines. Thus, the development of an efficient general and enantioselective synthetic technology giving access to a range of such heterocycles remained a challenge. Here we present a method enabling the reduction of 3-thiazolines with high conversion and high to excellent enantioselectivity (at least 96% and up to 99% enantiomeric excess). This technology is based on the use of imine reductases as catalysts, has a broad substrate range, and is also applied successfully to other sulfur-containing heterocyclic imines such as 2H-1,4-benzothiazines. Moreover the effiency of this biocatalytic technology platform is demonstrated in an initial process development leading to 99% conversion and 99% enantiomeric excess at a substrate loading of 18 g/L in the presence of designer cells.

SUBMITTER: Zumbragel N

PROVIDER: S-EPMC5955971 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

An (R)-Imine Reductase Biocatalyst for the Asymmetric Reduction of Cyclic Imines.

Project description:Although the range of biocatalysts available for the synthesis of enantiomerically pure chiral amines continues to expand, few existing methods provide access to secondary amines. To address this shortcoming, we have over-expressed the gene for an (R)-imine reductase [(R)-IRED] from Streptomyces sp. GF3587 in Escherichia coli to create a recombinant whole-cell biocatalyst for the asymmetric reduction of prochiral imines. The (R)-IRED was screened against a panel of cyclic imines and two iminium ions and was shown to possess high catalytic activity and enantioselectivity. Preparative-scale synthesis of the alkaloid (R)-coniine (90?% yield; 99?% ee) from the imine precursor was performed on a gram-scale. A homology model of the enzyme active site, based on the structure of a closely related (R)-IRED from Streptomyces kanamyceticus, was constructed and used to identify potential amino acids as targets for mutagenesis.

| S-EPMC4973613 | biostudies-literature

Enantioselective formal aza-Diels-Alder reactions of enones with cyclic imines catalyzed by primary aminothioureas.

Project description:A highly enantio- and diastereoselective synthesis of indolo- and benzoquinolizidine compounds has been developed through the formal aza-Diels-Alder reaction of enones with cyclic imines. This transformation is catalyzed by a new bifunctional primary aminothiourea that achieves simultaneous activation of both the enone and imine reaction components.

| S-EPMC3566267 | biostudies-literature

Catalytic Enantioselective Synthesis of Guvacine Derivatives through [4 + 2] Annulations of Imines with ?-Methylallenoates.

Project description:P-Chiral [2.2.1] bicyclic phosphines (HypPhos catalysts) have been applied to reactions between ?-alkylallenoates and imines, producing guvacine derivatives. These HypPhos catalysts were assembled from trans-4-hydroxyproline, with the modular nature of the synthesis allowing variations of the exocyclic P and N substituents. Among them, exo-( p-anisyl)-HypPhos was most efficacious for [4 + 2] annulations between ethyl ?-methylallenoate and imines. Through this method, ( R)-aplexone was identified as being responsible for the decrease in the cellular levels of cholesterol.

| S-EPMC6173629 | biostudies-literature

Direct Access to Highly Functionalized Heterocycles through the Condensation of Cyclic Imines and ?-Oxoesters.

Project description:A facile, gram-scale preparation of 2-hydroxy-5,6,7,7a-tetrahydro-3H-pyrrolizin-3-ones and 2-hydroxy-6,7,8,8a-tetrahydroindolizin-3(5H)-ones from a condensation cyclization of ?-oxoesters with five- and six-membered cyclic imines, respectively, is reported. This transformation enables a concise, three-step synthesis of the natural products phenopyrrozin and p-hydroxyphenopyrrozin. Further, biologically relevant scaffolds, such as ?-quaternary ?-homo prolines and ?-lactams, are also prepared in two- to three-steps from the versatile 2-hydroxy-5,6,7,7a-tetrahydro-3H-pyrrolizin-3-one core.

| S-EPMC6008790 | biostudies-literature

Catalytic, enantioselective 1,3-dipolar cycloadditions of nitrile imines with methyleneindolinones.

Project description:Catalytic, enantioselective 1,3-dipolar cycloadditions of nitrile imines with methyleneindolinones are reported. The spiro[pyrazolin-3,3'-oxindole] products are formed in good yields (up to 98%) and high enantioselectivity (up to 99% ee).

| S-EPMC3876797 | biostudies-literature

Enantioselective synthesis of cyclic carbamimidates via a three-component reaction of imines, terminal alkynes, and p-toluenesulfonylisocyanate using a monophosphine gold(I) catalyst().

Project description:A racemic Au(I)-catalyzed three-component reaction has been developed to prepare cyclic carbamimidates from imines, terminal alkynes, and sulfonylisocyanates. This reaction exploits the carbophilic ?-acidity of gold catalysts to first activate an alkyne toward deprotonation and secondly, to activate the internal alkyne generated toward intramolecular O-cyclization. Unlike similar previously reported multicomponent gold-catalyzed reactions, the stereocenter generated during the alkynylation is preserved in the product. This trait was exploited by developing an enantioselective variant, using an unusual trans-1-diphenylphosphino-2-arylsulfamidocyclohexane ligand. Moderate to excellent levels of enantioselectivity were obtained using a variety of N-arylbenzylidene anilines (41-95% ee, 18 examples).

| S-EPMC3376162 | biostudies-literature

Nickel-Catalyzed Asymmetric Hydrogenation of Cyclic Sulfamidate Imines: Efficient Synthesis of Chiral Cyclic Sulfamidates.

Project description:Chiral cyclic sulfamidates are useful building blocks to construct compounds, such as chiral amines, with important applications. Often these compounds can only be generated through expensive precious metal catalysts. Here, Ni(OAc)2/(S, S)-Ph-BPE-catalyzed highly efficient asymmetric hydrogenation of cyclic sulfamidate imines was successfully developed, affording various chiral cyclic sulfamidates with high yields and excellent enantioselectivities (up to 99% yield, >99% enantiomeric excess [ee]). This Ni-catalyzed asymmetric hydrogenation on a gram scale has been achieved with only 0.1 mol% catalyst loading in 99% yield with 93% ee. Other types of N-sulfonyl ketimines were also hydrogenated well to obtain the corresponding products with >99% conversion, 96%-97% yields, and 97%->99% ee. In addition, this asymmetric methodology could produce other enantioenriched organic molecules, such as chiral ?-fluoroamine, amino ether, and phenylglycinol. Moreover, a reasonable catalytic cycle was provided according to the deuterium-labeling studies, which could reveal a possible mechanism for this Ni-catalyzed asymmetric hydrogenation.

| S-EPMC6664198 | biostudies-literature

Mannich-type Reactions of Cyclic Nitrones: Effective Methods for the Enantioselective Synthesis of Piperidine-containing Alkaloids.

Project description:Even though there are dozens of biologically active 2-substituted and 2,6-disubstituted piperidines, only a limited number of approaches exist for their synthesis. Herein is described two Mannich-type additions to nitrones, one using ?-ketoacids under catalyst-free conditions and another using methyl ketones in the presence of chiral thioureas, which can generate a broad array of such 2-substituted materials, as well as other ring variants, in the form of ?-N-hydroxy-aminoketones. Both processes have broad scope, with the latter providing products with high enantioselectivity (up to 98?%). The combination of these methods, along with other critical steps, has enabled 8-step total syntheses of the 2,6-disubstituted piperidine alkaloids (-)-lobeline and (-)-sedinone.

| S-EPMC7199385 | biostudies-literature

Asymmetric synthesis of trifluoromethylated amines via catalytic enantioselective isomerization of imines.

Project description:A new approach toward the asymmetric synthesis of optically active trifluoromethylated amines was enabled by an unprecedented, highly enantioselective catalytic isomerization of trifluoromethyl imines with a new chiral organic catalyst. Not only aryl but also alkyl trifluoromethylated amines could be obtained in high enantioselectivities.

| S-EPMC3475161 | biostudies-literature

Enantioselective rhodium-catalyzed [4+2] cycloaddition of ?,?-unsaturated imines and isocyanates.

Project description:A [4+2] cycloaddition of ?,?-unsaturated imines and isocyanates catalyzed by a phosphoramidite-rhodium complex provides pyrimidinones in good yields and high enantioselectivities.

| S-EPMC3069138 | 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