Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Practical, asymmetric route to sitagliptin and derivatives: development and origin of diastereoselectivity.

ABSTRACT: The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate S═O, consistent with MsOH being crucial for high selectivity. The second is a novel C-H···F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand.

SUBMITTER: Gutierrez O

PROVIDER: S-EPMC4576936 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Practical, asymmetric route to sitagliptin and derivatives: development and origin of diastereoselectivity.

Gutierrez Osvaldo O Metil Dattatray D Dwivedi Namrata N Gudimalla Nagaraju N Chandrashekar E R R ER Dahanukar Vilas H VH Bhattacharya Apurba A Bandichhor Rakeshwar R Kozlowski Marisa C MC

Organic letters 20150323 7

The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate S═O, consistent with MsOH being crucial for high selectivity. The second is a novel C-H···F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand. ...[more]

PMID: 25799267

Similar Datasets

Practical Asymmetric Synthesis of Sitagliptin Phosphate Monohydrate.

Project description:Optically pure sitagliptin phosphate monohydrate is efficiently and practically synthesized through a chiral hemiacetal as the key intermediate in 54% overall yield starting from (E)-4-(2,4,5-trifluorophenyl)but-2-enal and N-boc-protected hydroxylamine. The chiral hemiacetal fragment is constructed by a tandem aza-Michael/hemiacetal reaction catalyzed by an organocatalyst and the influence of acidity of Brønsted acid on tandem aza-Michael/hemiacetal reaction is researched in detail.

| S-EPMC6099835 | biostudies-other

Copper-catalyzed asymmetric conjugate reduction as a route to novel beta-azaheterocyclic acid derivatives.

Project description:A chiral copper-hydride catalyst for the asymmetric conjugate reduction of alpha,beta-unsaturated carbonyl compounds has been used for the reduction of substrates containing beta-nitrogen substituents. A new set of reaction conditions has allowed for a variety of beta-azaheterocyclic acid derivatives to be synthesized in excellent yields and with high degrees of enantioselectivity. In addition, the effect that the nature of the nitrogen substituent has on the rate of the conjugate reduction reaction has been explored.

| S-EPMC395992 | biostudies-literature

Origin of High Diastereoselectivity in Reactions of Seven-Membered-Ring Enolates.

Project description:Unlike many reactions of their six-membered-ring counterparts, the reactions of chiral seven-membered-ring enolates are highly diastereoselective. Diastereoselectivity was observed for a range of substrates, including lactam, lactone, and cyclic ketone derivatives. The stereoselectivity arises from torsional and steric interactions that develop when electrophiles approach the diastereotopic π-faces of the enolates, which are distinguished by subtle differences in the orientation of nearby atoms of the ring.

| S-EPMC8940697 | biostudies-literature

Origin of the Diastereoselectivity of the Heterogeneous Hydrogenation of a Substituted Indolizine.

Project description:In this work, the stereoselective heterogeneous hydrogenation of a tetrasubstituted indolizine was studied. Partial hydrogenation products were obtained in three steps from a substituted pyridine-2-carboxaldehyde prepared from commercial pyridoxine hydrochloride. The hydrogenation of the indolizine ring was shown to be diastereoselective, forming trans-6b and cis-9. Theoretical calculations (ab initio and DFT) were used to rationalize the unusual trans stereoselectivity for 6b, and a keto-enol tautomerism under kinetic control has been proposed as the source of diastereoselectivity.

| S-EPMC7498159 | biostudies-literature

A catalytic asymmetric route to carbapenems.

Project description:Efficient syntheses of N-acetyl thienamycin and epithienamycin A in their readily deprotected form are reported where three contiguous stereocenters are established in a single catalytic asymmetric azetidinone-forming reaction. These examples are a template for synthesizing C-5/C-6 cis or trans carbapenems with independent control of the C-8 stereocenter. A library of oxidatively and sterochemically defined azetidinone precursors to a variety of naturally occurring carbapenems and potential biosynthetic intermediates has been prepared to facilitate studies of carbapenem antibiotic biosynthesis.

| S-EPMC2736320 | biostudies-literature

Practical Route for Catalytic Ring-Opening Metathesis Polymerization.

Project description:Norbornene derivatives are typical monomers for ring-opening metathesis polymerization (ROMP) for synthesizing highly functional polymers. However, the lack of catalytic methods, that is, the lack of readily available chain transfer agents (CTAs) for these monomers has been a significant cost limitation when large-scale syntheses are required. Here, we report commercially available styrene and its derivatives as efficient regioselective CTAs for the catalytic synthesis of metathesis polymers requiring up to 1000 times less ruthenium than in classical ROMP experiments. The molecular weight of the synthesized polymers was controlled by the monomer-to-CTA ratio. Low molecular weight ROMP polymers known for their antimicrobial properties were also synthesized on a gram scale in this report. Polymers were characterized by SEC, 1H NMR spectroscopy, and isotopically resolved MALDI-TOF MS. This approach describes a greener, more cost-effective, and eco-friendly methodology for the preparation of metathesis-based materials on the multigram scale.

| S-EPMC9795566 | biostudies-literature

Ligand tuning in asymmetric hydrovinylation of 1,3-dienes: a stereoselective route to either steroid-C20 (S) or -C20 (R) derivatives.

Project description:1,3-Dienes derived from steroidal D-ring C 17-ketones undergo Ni(II)-catalyzed hydrovinylation to give 1,2- or 1,4-addition of ethylene. Using finely tuned phosphoramidite ligands, it is possible to synthesize either the C 20 ( R)- or ( S)-derivatives without mutual contamination. The proportion of the 1,4-adduct, which is also formed stereoselectively, can be minimized by optimizing the reaction conditions. Because the two alkenes in the resultant dienes have differing steric demands for many potential reactions, and are ideally juxtaposed for further D-ring functionalization, these intermediates could be useful for the preparation of biologically important compounds such as vitamin D analogs and various antitumor steroidal glycosides.

| S-EPMC2652850 | biostudies-literature

Pseudoephenamine: a practical chiral auxiliary for asymmetric synthesis.

Project description: Not available

| S-EPMC3854953 | biostudies-literature

A Photochemical Macrocyclization Route to Asymmetric Strained [3.2] Paracyclophanes.

Project description:The intricate frameworks of paracyclophanes are an important target for synthesis since they are found in various chiral auxiliaries, solar cells, high-performance plastics, pharmaceuticals, and molecular machines. Whereas numerous methods exist for the preparation of symmetric paracyclophanes, protocols for the efficient synthesis of strained asymmetric scaffolds are limited. Here we report a remarkably simple photochemical route to strained [3.2]paracyclophanes starting from readily available educts. By way of NMR and X-ray analyses, we discovered that UV-irradiation of an aromatic carboxylic ester tethered to a toluene moiety leads to the intramolecular formation of a new C-C bond, with loss of an alcohol. A systematic evaluation of the reaction conditions and substituents, as well as radical starter and triplet quenching experiments, point to a reaction mechanism involving an excited triplet state and hydrogen atom transfer. The new method proved to be robust and versatile enabling the synthesis of a range of cyclophanes with different substitutions, including an unusual diastereoisomer with two planar chiral centers, and thus proved to be a valuable addition to the synthetic toolbox.

| S-EPMC10092696 | biostudies-literature

Asymmetric visual input and route recapitulation in homing pigeons.

Project description:Pigeons (Columba livia) display reliable homing behaviour, but their homing routes from familiar release points are individually idiosyncratic and tightly recapitulated, suggesting that learning plays a role in route establishment. In light of the fact that routes are learned, and that both ascending and descending visual pathways share visual inputs from each eye asymmetrically to the brain hemispheres, we investigated how information from each eye contributes to route establishment, and how information input is shared between left and right neural systems. Using on-board global positioning system loggers, we tested 12 pigeons' route fidelity when switching from learning a route with one eye to homing with the other, and back, in an A-B-A design. Two groups of birds, trained first with the left or first with the right eye, formed new idiosyncratic routes after switching eyes, but those that flew first with the left eye formed these routes nearer to their original routes. This confirms that vision plays a major role in homing from familiar sites and exposes a behavioural consequence of neuroanatomical asymmetry whose ontogeny is better understood than its functional significance.

| S-EPMC4614786 | 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