Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Catalytic asymmetric formal synthesis of beraprost.

ABSTRACT: The first catalytic asymmetric synthesis of the key intermediate for beraprost has been achieved through an enantioselective intramolecular oxa-Michael reaction of an ?,?-unsaturated amide mediated by a newly developed benzothiadiazine catalyst. The Weinreb amide moiety and bromo substituent of the Michael adduct were utilized for the C-C bond formations to construct the scaffold. All four contiguous stereocenters of the tricyclic core were controlled via Rh-catalyzed stereoselective C-H insertion and the subsequent reduction from the convex face.

SUBMITTER: Kobayashi Y

PROVIDER: S-EPMC4685892 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Catalytic asymmetric formal synthesis of beraprost.

Kobayashi Yusuke Y Kuramoto Ryuta R Takemoto Yoshiji Y

Beilstein journal of organic chemistry 20151218

The first catalytic asymmetric synthesis of the key intermediate for beraprost has been achieved through an enantioselective intramolecular oxa-Michael reaction of an α,β-unsaturated amide mediated by a newly developed benzothiadiazine catalyst. The Weinreb amide moiety and bromo substituent of the Michael adduct were utilized for the C-C bond formations to construct the scaffold. All four contiguous stereocenters of the tricyclic core were controlled via Rh-catalyzed stereoselective C-H inserti ...[more]

PMID: 26734111

Similar Datasets

A catalytic, asymmetric formal synthesis of (+)-hamigeran B.

Project description:A concise asymmetric, formal synthesis of (+)-hamigeran B is reported. A Pd-catalyzed, decarboxylative allylic alkylation, employing a trifluoromethylated derivative of t-BuPHOX, is utilized as the enantioselective step to form the critical quaternary carbon center in excellent yield and enantioselectivity. The product is converted in three steps to a late-stage intermediate previously used in the synthesis of hamigeran B.

| S-EPMC3045637 | biostudies-literature

Catalytic Asymmetric Formal Total Synthesis of (-)-Triptophenolide and (+)-Triptolide.

Project description:Catalytic asymmetric formal synthesis of (-)-Triptophenolide and (+)-Triptolide have been achieved. Key reaction involves Palladium catalyzed asymmetric conjugate addition of aryl boronic acid to 3-methyl cyclohexe-1-none to form quaternary carbon. Claisen rearrangement and subsequent aldol reaction furnished trans-decaline key intermediate, which assured a formal total synthesis of (-)-Triptophenolide and (+)-Triptolide.

| S-EPMC5385656 | biostudies-literature

Catalytic Asymmetric Formal [3+2] Cycloaddition of Azoalkenes with 3-Vinylindoles: Synthesis of 2,3-Dihydropyrroles.

Project description:Chiral phosphoric acid-catalyzed highly enantioselective formal [3 + 2] cycloaddition reaction of azoalkenes with 3-vinylindoles has been established. Under mild conditions, the projected cycloaddition proceeded smoothly, affording a variety of 2,3-dihydropyrroles in high yields and excellent enantioselectivities, and also in a diastereospecific manner. As opposed to the common 4-atom synthons in the previous literature reports, azoalkenes served as 3-atom synthons. Besides, the observed selectivity was supported by primary theoretical calculation. The unique chemistry of azoalkenes disclosed herein will empower asymmetric synthesis of nitrogen-containing ring structural motifs in a broader context.

| S-EPMC7021545 | biostudies-literature

De Novo Synthesis of Dihydrobenzofurans and Indolines and Its Application to a Modular, Asymmetric Synthesis of Beraprost.

Project description:Dihydrobenzofurans and indolines are important constituents of pharmaceuticals. Herein, we describe a novel strategy for their construction in which the aromatic ring is created de novo through an inverse-electron demand Diels-Alder reaction and cheletropic extrusion sequence of a 2-halothiophene-1,1-dioxide with an enol ether/enamide, followed by aromatization. Unusually, the aromatization process proved to be highly challenging, but it was discovered that treatment of the halocyclohexadienes with a base effected an α-elimination-aromatization reaction. Mechanistic investigation of this step using deuterium-labeling studies indicated the intermediacy of a carbene which undergoes a 1,2-hydrogen shift and subsequent aromatization. The methodology was applied to a modular and stereoselective total synthesis of the antiplatelet drug beraprost in only 8 steps from a key enal-lactone. This lactone provided the core of beraprost to which both its sidechains could be appended through a 1,4-conjugate addition process (lower ω-sidechain), followed by de novo construction of beraprost's dihydrobenzofuran (upper α-sidechain) using our newly developed methodology. Additionally, we have demonstrated the breadth of our newly established protocol in the synthesis of functionalized indolines, which occurred with high levels of regiocontrol. According to density-functional theory (DFT) calculations, the high selectivity originates from attractive London dispersion interactions in the TS of the Diels-Alder reaction.

| S-EPMC10311537 | biostudies-literature

Catalytic Asymmetric Synthesis of meta Benzene Isosteres

Project description:Aromatic rings are common elements in pharmaceutically active compounds; however, their ready oxidation can present a liability with respect to a drug's metabolic stability. Replacing these aromatic rings in pharmaceutical compounds with non-aromatic isosteric motifs can enhance properties such as potency, metabolic stability, solubility, and lipophilicity. Since the binding pockets of most pharmaceutical targets are chiral, the stereochemical configuration of the isosteric replacements are expected to have an impact on the affinity of derived ligands for target receptors. A significant impediment to this approach is the lack of simple, and scalable catalytic enantioselective syntheses of candidate isosteres from readily available precursors. In this work, we present a heretofore unknown palladium-catalyzed reaction that converts hydrocarbon-derived precursors to chiral boron-containing nortricyclanes and we show that that shape of these nortricyclanes makes them plausible isosteres for meta disubstituted aromatic rings. With chiral catalysts, the Pd-catalyzed reaction can be accomplished in an enantioselective fashion and subsequent transformation of the boron group provides access to a broad array of structures. We also show that incorporation of nortricyclanes into pharmaceutical motifs can result in improved biophysical properties along with stereochemistry-dependent activity. We anticipate that these features, coupled with the simple, inexpensive synthesis of the functionalized nortricyclane scaffold will render this platform a useful foundation for assembly of new biologically active agents.

2024-09-11 | PXD051400 | Pride

Formal enantioconvergent substitution of alkyl halides via catalytic asymmetric photoredox radical coupling.

Project description:Classic nucleophilic substitution reactions (SN1 and SN2) are not generally amenable to the enantioselective variants that use simple and racemic alkyl halide electrophiles. The merging of transition metal catalysis and radical chemistry with organometallic nucleophiles is a versatile method for addressing this limitation. Here, we report that visible light-driven catalytic asymmetric photoredox radical coupling can act as a complementary and generic strategy for the enantioconvergent formal substitution of alkyl haldies with readily available and bench-stable organic molecules. Single-electron reductive debrominations of racemic ?-bromoketones generate achiral alkyl radicals that can participate in asymmetric Csp3-Csp3 bonds forming cross-coupling reactions with ?-amino radicals derived from N-aryl amino acids. A wide range of valuable enantiomerically pure ?2- and ?2,2-amino ketones were obtained in satisfactory yields with good-to-excellent enantioselectivities by using chiral phosphoric acid catalysts to control the stereochemistry and chemoselectivity. Fluoro-hetero-quaternary and full-carbon quaternary stereocenters that are challenging to prepare were successfully constructed.

| S-EPMC6015005 | biostudies-literature

Catalytic asymmetric synthesis of geminal-dicarboxylates.

Project description:Stereogenic acetals, spiroacetals and ketals are well-studied stereochemical features that bear two heteroatoms at a common carbon atom. These stereocenters are normally found in cyclic structures while linear (or acyclic) analogues bearing two heteroatoms are rare. Chiral geminal-dicarboxylates are illustrative, there is no current way to access this class of compounds while controlling the stereochemistry at the carbon center bound to two oxygen atoms. Here we report a rhodium-catalysed asymmetric carboxylation of ester-containing allylic bromides to form stereogenic carbon centers bearing two different carboxylates with high yields and enantioselectivities. The products, which are surprisingly stable to a variety of acidic and basic conditions, can be manipulated with no loss of enantiomeric purity as demonstrated by ring closing metathesis reactions to form chiral lactones, which have been extensively used as building blocks in asymmetric synthesis.

| S-EPMC6063137 | biostudies-literature

Asymmetric Formal Synthesis of the Long-Acting DPP-4 Inhibitor Omarigliptin.

Project description:A highly efficient asymmetric synthesis of the key tetrahydropyranol intermediate of DPP-4 inhibitor omarigliptin (1) is described. The successful development of a protecting-group- and precious-metal-free synthesis was achieved via the discovery of a practical asymmetric Henry reaction and the application of a one-pot nitro-Michael-lactolization-dehydration through-process. Other features of the synthesis include a highly efficient MsCl-mediated dehydration and a crystallization-induced dynamic resolution for exceptional ee and dr upgrade. The synthesis of this complex intermediate utilizes simple starting materials and proceeds in four linear steps.

| S-EPMC5933450 | biostudies-literature

A catalytic, enantioselective formal synthesis of (+)-dichroanone and (+)-taiwaniaquinone H.

Project description:A catalytic, enantioselective formal synthesis of (+)-dichroanone and (+)-taiwaniaquinone H is reported. The all-carbon quaternary stereocenter was constructed by asymmetric conjugate addition catalyzed by a palladium(II) (S)-tert-butylpyridinooxazoline complex. The unexpected formation of a [3.2.1] bicyclic intermediate required the identification of a new route. Analysis of the Hammett constants for para-substituted arenes enabled the rational design of a highly enantioselective conjugate addition substrate that led to the completion of the formal synthesis.

| S-EPMC4275150 | biostudies-literature

Catalytic asymmetric allylic and homoallylic diamination of terminal olefins via formal C-H activation.

Project description:This paper describes a catalytic asymmetric diamination process for terminal olefins at allylic and homoallylic carbons via formal C-H activation using di-tert-butyldiaziridinone as nitrogen source with a catalyst generated from Pd2(dba)3 and chiral phosphorus amidite ligand. A wide variety of readily available terminal olefins can be effectively diaminated in good yields with high regio-, diastereo-, and enantioselectivities.

| S-EPMC2776772 | 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