Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Structure-Activity Relationship Studies of Cyclopropenimines as Enantioselective Bronsted Base Catalysts.

ABSTRACT: We recently demonstrated that chiral cyclopropenimines are viable Brønsted base catalysts in enantioselective Michael and Mannich reactions. Herein, we describe a series of structure-activity relationship studies that provide an enhanced understanding of the effectiveness of certain cyclopropenimines as enantioselective Brønsted base catalysts. These studies underscore the crucial importance of dicyclohexylamino substituents in mediating both reaction rate and enantioselectivity. In addition, an unusual catalyst CH···O interaction, which provides both ground state and transition state organization, is discussed. Cyclopropenimine stability studies have led to the identification of new catalysts with greatly improved stability. Finally, additional demonstrations of substrate scope and current limitations are provided herein.

SUBMITTER: Bandar JS

PROVIDER: S-EPMC4618405 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

N-Heterocyclic carbenes as chiral Bronsted base catalysts: a highly diastereo- and enantioselective 1,6-addition reaction.

Project description:Highly diastereo- and enantioselective 1,6-addition of 1,3-ketoamides to p-quinone methides (p-QMs) using chiral NHCs as Brønsted base catalysts is developed. The reaction is based on the utilization of a 1,3-ketoamide having acidic N-H that forms a chiral ion-pair consisting of the enolate and the azolium ion. Different β-ketoamides and functionalized p-QMs are applicable to the reaction. Synthetic application of the method is demonstrated via the preparation of highly enantioenriched β and γ-lactam derivatives.

| S-EPMC6144034 | biostudies-literature

Enantioselective bromocycloetherification by Lewis base/chiral Bronsted acid cooperative catalysis.

Project description:A binary catalyst system for the enantioselective bromocycloetherification of 5-arylpentenols is described. The combination of an achiral Lewis base and a chiral Brønsted acid affords good enantioselectivities for the cyclization of Z configured 5-arylpentenols to form bromomethyltetrahydrofurans. The constitutional site selectivity is highly dependent upon the aromatic substituent and the configuration of the double bond.

| S-EPMC3238797 | biostudies-literature

Transition state analysis of enantioselective Bronsted base catalysis by chiral cyclopropenimines.

Project description:Experimental (13)C kinetic isotope effects have been used to interrogate the rate-limiting step of the Michael addition of glycinate imines to benzyl acrylate catalyzed by a chiral 2,3-bis(dicyclohexylamino) cyclopropenimine catalyst. The reaction is found to proceed via rate-limiting carbon-carbon bond formation. The origins of enantioselectivity and a key noncovalent CH···O interaction responsible for transition state organization are identified on the basis of density functional theory calculations and probed using experimental labeling studies. The resulting high-resolution experimental picture of the enantioselectivity-determining transition state is expected to guide new catalyst design and reaction development.

| S-EPMC4230825 | biostudies-literature

Lewis Base-Bronsted Acid-Enzyme Catalysis in Enantioselective Multistep One-Pot Syntheses.

Project description:Establishing one-pot, multi-step protocols combining different types of catalysts is one important goal for increasing efficiency in modern organic synthesis. In particular, the high potential of biocatalysts still needs to be harvested. Based on an in-depth mechanistic investigation of a new organocatalytic protocol employing two catalysts {1,4-diazabicyclo[2.2.2]octane (DABCO); benzoic acid (BzOH)}, a sequence was established providing starting materials for enzymatic refinement (ene reductase; alcohol dehydrogenase): A gram-scale access to a variety of enantiopure key building blocks for natural product syntheses was enabled utilizing up to six catalytic steps within the same reaction vessel.

| S-EPMC8360128 | biostudies-literature

Chiral Bronsted base-promoted nitroalkane alkylation: enantioselective synthesis of sec-alkyl-3-substituted indoles.

Project description:A Brønsted base-catalyzed reaction of nitroalkanes with alkyl electrophiles provides indole heterocycles substituted at C3 bearing a sec-alkyl group with good enantioselectivity (up to 90% ee). Denitration by hydrogenolysis provides a product with equally high ee. An indolenine intermediate is implicated in the addition step, and surprisingly, water cosolvent was found to have a beneficial effect in this step, leading to a one-pot protocol for elimination/enantioselective addition using PBAM, a bis(amidine) chiral nonracemic base.

| S-EPMC3005818 | biostudies-literature

Enantioselective small molecule synthesis by carbon dioxide fixation using a dual Bronsted acid/base organocatalyst.

Project description:Carbon dioxide exhibits many of the qualities of an ideal reagent: it is nontoxic, plentiful, and inexpensive. Unlike other gaseous reagents, however, it has found limited use in enantioselective synthesis. Moreover, unprecedented is a tool that merges one of the simplest biological approaches to catalysis-Brønsted acid/base activation-with this abundant reagent. We describe a metal-free small molecule catalyst that achieves the three component reaction between a homoallylic alcohol, carbon dioxide, and an electrophilic source of iodine. Cyclic carbonates are formed enantioselectively.

| S-EPMC4708058 | biostudies-literature

Structure-activity relationship studies of SETD8 inhibitors.

Project description:SETD8 (also known as SET8, PR-SET7, or KMT5A (lysine methyltransferase 5A)) is the only known lysine methyltransferase that catalyzes monomethylation of histone H4 lysine 20 (H4K20). In addition to H4K20, SETD8 monomethylates non-histone substrates such as the tumor suppressor p53 and proliferating cell nuclear antigen (PCNA). Because of its role in regulating diverse biological processes, SETD8 has been pursued as a potential therapeutic target. We recently reported the first substrate-competitive SETD8 inhibitor, UNC0379 (1), which is selective for SETD8 over 15 other methyltransferases. We characterized this inhibitor in a battery of biochemical and biophysical assays. Here we describe our comprehensive structure-activity relationship (SAR) studies of this chemical series. In addition to 2- and 4-substituents, we extensively explored 6- and 7-substituents of the quinazoline scaffold. These SAR studies led to the discovery of several new compounds, which displayed similar potencies as compound 1, and interesting SAR trends.

| S-EPMC4278651 | biostudies-literature

Relaxin family peptides: structure-activity relationship studies.

Project description:The human relaxin peptide family consists of seven cystine-rich peptides, four of which are known to signal through relaxin family peptide receptors, RXFP1-4. As these peptides play a vital role physiologically and in various diseases, they are of considerable importance for drug discovery and development. Detailed structure-activity relationship (SAR) studies towards understanding the role of important residues in each of these peptides have been reported over the years and utilized for the design of antagonists and minimized agonist variants. This review summarizes the current knowledge of the SAR of human relaxin 2 (H2 relaxin), human relaxin 3 (H3 relaxin), human insulin-like peptide 3 (INSL3) and human insulin-like peptide 5 (INSL5). LINKED ARTICLES:This article is part of a themed section on Recent Progress in the Understanding of Relaxin Family Peptides and their Receptors. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.10/issuetoc.

| S-EPMC5406294 | biostudies-literature

Truncated Orexin Peptides: Structure-Activity Relationship Studies.

Project description:Orexin receptors are involved in many processes including energy homeostasis, wake/sleep cycle, metabolism and reward. Development of potent and selective ligands is an essential step for defining the mechanism(s) underlying such critical processes. The goal of this study was to further investigate the structure-activity relationships of these peptides and to identify truncated form of the orexin peptides active at OX1. Truncation studies have led to OXA (17-33) as the shortest active peptide known to date with a 23-fold selectivity for OX1 over OX2. Alanine, D-amino acid and proline scans have highlighted the particular importance of Tyr17, Leu20, Asn25 and His26 for agonist properties of OXA(17-33). The conformation of the C-terminus might also be a defining factor in agonist activity and selectivity of the orexin peptides for the OX1 receptor.

| S-EPMC3975045 | biostudies-literature

Development and mechanism of an enantioselective bromocycloetherification reaction via Lewis base/chiral Bronsted acid cooperative catalysis.

Project description:The development of a binary catalyst system for bromocycloetherification, consisting of an achiral Lewis base and a chiral Brønsted acid, is described in detail. The results of preliminary kinetic studies are also presented.

| S-EPMC4676414 | 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