Browse
Submit Data
Databases
API
Help

Dataset Information

7 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A general and enantioselective approach to pentoses: a rapid synthesis of PSI-6130, the nucleoside core of sofosbuvir.

ABSTRACT: An efficient route towards biologically relevant pentose derivatives is described. The de novo synthetic strategy features an enantioselective ?-oxidation reaction enabled by a chiral amine in conjunction with copper(II) catalysis. A subsequent Mukaiyama aldol coupling allows for the incorporation of a wide array of modular two-carbon fragments. Lactone intermediates accessed via this route provide a useful platform for elaboration, as demonstrated by the preparation of a variety of C-nucleosides and fluorinated pentoses. Finally, this work has facilitated expedient syntheses of pharmaceutically active compounds currently in clinical use.

SUBMITTER: Peifer M

PROVIDER: S-EPMC4210058 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

A general and enantioselective approach to pentoses: a rapid synthesis of PSI-6130, the nucleoside core of sofosbuvir.

Peifer Manuel M Berger Raphaëlle R Shurtleff Valerie W VW Conrad Jay C JC MacMillan David W C DW

Journal of the American Chemical Society 20140409 16

An efficient route towards biologically relevant pentose derivatives is described. The de novo synthetic strategy features an enantioselective α-oxidation reaction enabled by a chiral amine in conjunction with copper(II) catalysis. A subsequent Mukaiyama aldol coupling allows for the incorporation of a wide array of modular two-carbon fragments. Lactone intermediates accessed via this route provide a useful platform for elaboration, as demonstrated by the preparation of a variety of C-nucleoside ...[more]

PMID: 24670208

Similar Datasets

A general, enantioselective synthesis of ?- and ?-fluoroamines.

Project description:In this Letter, we describe a short, high yielding protocol for the enantioselective (87-96% ee) and general synthesis of ?-fluoroamines and previously difficult to access ?-fluoroamines from commercial aldehydes via organocatalysis.

| S-EPMC3769685 | biostudies-literature

A general, enantioselective synthesis of protected morpholines and piperazines.

Project description:A short, high yielding protocol has been developed for the enantioselective and general synthesis of C2-functionalized, benzyl protected morpholines and orthogonally N,N'-protected piperazines from a common intermediate.

| S-EPMC3369273 | biostudies-literature

Perylenequinone natural products: enantioselective synthesis of the oxidized pentacyclic core.

Project description:An enantioselective approach to the perylenequinone core found in the mold perylenequinone natural products is outlined. Specifically, the first asymmetric syntheses of helical chiral perylenequinones absent any additional stereogenic centers are described. Key elements of the synthetic venture include a catalytic enantioselective biaryl coupling, a PIFA-induced naphthalene hydroxylation, and a palladium-mediated aromatic decarboxylation. Transfer of the binaphthalene axial stereochemistry to the perylenequinone helical stereochemistry proceeded with good fidelity. Furthermore, the resultant perylenequinones were shown to possess sufficient atropisomeric stability to be viable intermediates in the biogenesis of the perylenequinone natural products. This stability supports the use of the helical axis as a stereochemical relay in synthesis of the natural products containing additional stereochemical centers.

| S-EPMC2798903 | biostudies-literature

A general approach for retrosynthetic molecular core analysis.

Project description:Scaffold analysis of compound data sets has reemerged as a chemically interpretable alternative to machine learning for chemical space and structure-activity relationships analysis. In this context, analog series-based scaffolds (ASBS) are synthetically relevant core structures that represent individual series of analogs. As an extension to ASBS, we herein introduce the development of a general conceptual framework that considers all putative cores of molecules in a compound data set, thus softening the often applied "single molecule-single scaffold" correspondence. A putative core is here defined as any substructure of a molecule complying with two basic rules: (a) the size of the core is a significant proportion of the whole molecule size and (b) the substructure can be reached from the original molecule through a succession of retrosynthesis rules. Thereafter, a bipartite network consisting of molecules and cores can be constructed for a database of chemical structures. Compounds linked to the same cores are considered analogs. We present case studies illustrating the potential of the general framework. The applications range from inter- and intra-core diversity analysis of compound data sets, structure-property relationships, and identification of analog series and ASBS. The molecule-core network herein presented is a general methodology with multiple applications in scaffold analysis. New statistical methods are envisioned that will be able to draw quantitative conclusions from these data. The code to use the method presented in this work is freely available as an additional file. Follow-up applications include analog searching and core structure-property relationships analyses.

| S-EPMC6760108 | biostudies-literature

Rapid synthesis of the core scaffold of crinane and haemanthamine through a multi-component approach.

Project description:A rapid synthesis of the core structures of crinane and haemanthamine has been developed, enabled by a multicomponent approach. This work constitutes a formal synthesis of crinane and sets the stage for access to both families of natural products and key analogues. A key highlight of the approach is the modularity of the core synthesis, overcoming existing challenges for these scaffolds and providing a path to explore site-selective oxidation to expand the scope of molecules accessible from common intermediates.

| S-EPMC8224825 | biostudies-literature

Biomimetic Approach to the Catalytic Enantioselective Synthesis of Flavonoids.

Project description:Herein is reported the direct asymmetric addition of phenol nucleophiles to benzopyrylium salts as a means to produce enantioenriched flavonoid-like compounds. This enantioselective C-C bond construction was achieved through a chiral anion phase-transfer strategy that mimics the proposed biosynthesis of this structurally diverse set of natural products. The utility of this methodology was demonstrated in enantioselective synthesis of a 2,8-dioxabicyclo[3.3.1]nonane and a 2,4-diarylbenzopyran.

| S-EPMC5149420 | biostudies-literature

A general approach to the enantioselective ?-oxidation of aldehydes via synergistic catalysis.

Project description:A new enantioselective ?-oxidation of aldehydes has been accomplished using TEMPO and a synergistic combination of copper and organic catalysis. Expanding upon recently reported mechanistic studies, these mild catalytic conditions provide stable aldehyde products bearing a wide array of electronically and sterically diverse substructures. The utility of these oxidized products is highlighted by subsequent derivatization to a variety of common chiral synthons, without loss in enantiopurity.

| S-EPMC3269783 | biostudies-literature

Sustainable Synthesis of Chiral Tetrahydrofurans through the Selective Dehydration of Pentoses.

Project description:L-Arabinose is an abundant resource available as a waste product of the sugar beet industry. Through use of a hydrazone-based strategy, L-arabinose was selectively dehydrated to form a chiral tetrahydrofuran on a multi-gram scale without the need for protecting groups. This approach was extended to other biomass-derived reducing sugars and the mechanism of the key cyclization investigated. This methodology was applied to the synthesis of a range of functionalized chiral tetrahydrofurans, as well as a formal synthesis of 3R-3-hydroxymuscarine.

| S-EPMC4648048 | biostudies-literature

Enantioselective, Convergent Synthesis of the Ineleganolide Core by a Tandem Annulation Cascade.

Project description:An enantioselective and diastereoselective approach toward the synthesis of the polycyclic norditerpenoid ineleganolide is disclosed. A palladium-catalyzed enantioselective allylic alkylation is employed to stereoselectively construct the requisite chiral tertiary ether and facilitate the synthesis of a 1,3-cis-cyclopentenediol building block. Careful substrate design enabled the convergent assembly of the ineleganolide [6,7,5,5]-tetracyclic scaffold by a diastereoselective cyclopropanation-Cope rearrangement cascade under unusually mild conditions. Computational evaluation of ground state energies of late-stage synthetic intermediates was used to guide synthetic development and aid in the investigation of the conformational rigidity of these highly constrained and compact polycyclic structures. This work represents the first successful synthesis of the core structure of any member of the polycyclic norcembranoid diterpene family of natural products. Advanced synthetic manipulations generated a series of natural product-like compounds that were shown to possess selective secretory antagonism of either interleukin-5 or interleukin-17. This bioactivity stands in contrast to the known antileukemic activity of ineleganolide and suggests the norcembranoid natural product core may serve as a useful scaffold for the development of diverse therapeutics.

| S-EPMC5321630 | biostudies-literature

Enzymatic Synthesis of the Ribosylated Glycyl-Uridine Disaccharide Core of Peptidyl Nucleoside Antibiotics.

Project description:Muraymycins belong to a family of nucleoside antibiotics that have a distinctive disaccharide core consisting of 5-amino-5-deoxyribofuranose (ADR) attached to 6'- N-alkyl-5'- C-glycyluridine (GlyU). Here, we functionally assign and characterize six enzymes from the muraymycin biosynthetic pathway involved in the core assembly that starts from uridine monophosphate (UMP). The biosynthesis is initiated by Mur16, a nonheme Fe(II)- and ?-ketoglutarate-dependent dioxygenase, followed by four transferase enzymes: Mur17, a pyridoxal-5'-phosphate (PLP)-dependent transaldolase; Mur20, an aminotransferase; Mur26, a pyrimidine phosphorylase; and Mur18, a nucleotidylyltransferase. The pathway culminates in glycosidic bond formation in a reaction catalyzed by an additional transferase enzyme, Mur19, a ribosyltransferase. Analysis of the biochemical properties revealed several noteworthy discoveries including that (i) Mur16 and downstream enzymes can also process 2'-deoxy-UMP to generate a 2-deoxy-ADR, which is consistent with the structure of some muraymycin congeners; (ii) Mur20 prefers l-Tyr as the amino donor source; (iii) Mur18 activity absolutely depends on the amine functionality of the ADR precursor consistent with the nucleotidyltransfer reaction occurring after the Mur20-catalyzed aminotransfer reaction; and (iv) the bona fide sugar acceptor for Mur19 is (5' S,6' S)-GlyU, suggesting that ribosyltransfer occurs prior to N-alkylation of GlyU. Finally, a one-pot, six-enzyme reaction was utilized to generate the ADR-GlyU disaccharide core starting from UMP.

| S-EPMC6291243 | 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