Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Practical Electrochemical Anodic Oxidation of Polycyclic Lactams for Late Stage Functionalization.

ABSTRACT: Electrochemistry provides a powerful tool for the late-stage functionalization of complex lactams. A two-stage protocol for converting lactams, many of which can be prepared through the intramolecular Schmidt reaction of keto azides, is presented. In the first step, anodic oxidation in MeOH using a repurposed power source provides a convenient route to lactams bearing a methoxy group adjacent to nitrogen. Treatment of these intermediates with a Lewis acid in dichloromethane permits the regeneration of a reactive acyliminium ion that is then reacted with a range of nucleophilic species.

SUBMITTER: Frankowski KJ

PROVIDER: S-EPMC4629799 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Practical Electrochemical Anodic Oxidation of Polycyclic Lactams for Late Stage Functionalization.

Frankowski Kevin J KJ Liu Ruzhang R Milligan Gregory L GL Moeller Kevin D KD Aubé Jeffrey J

Angewandte Chemie (International ed. in English) 20150901 36

Electrochemistry provides a powerful tool for the late-stage functionalization of complex lactams. A two-stage protocol for converting lactams, many of which can be prepared through the intramolecular Schmidt reaction of keto azides, is presented. In the first step, anodic oxidation in MeOH using a repurposed power source provides a convenient route to lactams bearing a methoxy group adjacent to nitrogen. Treatment of these intermediates with a Lewis acid in dichloromethane permits the regenerat ...[more]

PMID: 26371961

Similar Datasets

General α-Amino 1,3,4-Oxadiazole Synthesis via Late-Stage Reductive Functionalization of Tertiary Amides and Lactams*.

Project description:An iridium-catalyzed reductive three-component coupling reaction for the synthesis of medicinally relevant α-amino 1,3,4-oxadiazoles from abundant tertiary amides or lactams, carboxylic acids, and (N-isocyanimino) triphenylphosphorane, is described. Proceeding under mild conditions using (<1 mol %) Vaska's complex (IrCl(CO)(PPh3 )2 ) and tetramethyldisiloxane to access the key reactive iminium ion intermediates, a broad range of α-amino 1,3,4-oxadiazole architectures were accessed from carboxylic acid feedstock coupling partners. Extension to α-amino heterodiazole synthesis was readily achieved by exchanging the carboxylic acid coupling partner for C-, S-, or N-centered Brønsted acids, and provided rapid and modular access to these desirable, yet difficult-to-access, heterocycles. The high chemoselectivity of the catalytic reductive activation step allowed late-stage functionalization of 10 drug molecules, including the synthesis of heterodiazole-fused drug-drug conjugates.

| S-EPMC8457168 | biostudies-literature

Electrochemical C-H phosphorylation of arenes in continuous flow suitable for late-stage functionalization.

Project description:The development of efficient and sustainable methods for carbon-phosphorus bond formation is of great importance due to the wide application of organophosphorus compounds in chemistry, material sciences and biology. Previous C-H phosphorylation reactions under nonelectrochemical or electrochemical conditions require directing groups, transition metal catalysts, or chemical oxidants and suffer from limited scope. Herein we disclose a catalyst- and external oxidant-free, electrochemical C-H phosphorylation reaction of arenes in continuous flow for the synthesis of aryl phosphorus compounds. The C-P bond is formed through the reaction of arenes with anodically generated P-radical cations, a class of reactive intermediates remained unexplored for synthesis despite intensive studies of P-radicals. The high reactivity of the P-radical cations coupled with the mild conditions of the electrosynthesis ensures not only efficient reactions of arenes of diverse electronic properties but also selective late-stage functionalization of complex natural products and bioactive compounds. The synthetic utility of the electrochemical method is further demonstrated by the continuous production of 55.0 grams of one of the phosphonate products.

| S-EPMC8616953 | biostudies-literature

SuFEx Click Chemistry Enabled Late-Stage Drug Functionalization.

Project description:Sulfur(VI) Fluoride Exchange (SuFEx) is a new family of click chemistry transformations which relies on readily available materials to produce compounds bearing the SVI-F motif. The potential of SuFEx in drug discovery has just started to be explored. We report the first method of SuFEx chemistry for the conversion of phenolic compounds to their respective arylfluorosulfate derivatives in situ in 96-well plates. This method is compatible with automated synthesis and screening to quickly assess the biological activities of the in situ generated, crude products. Using this method, we perform late-stage functionalization of a panel of known anticancer drugs to generate the corresponding arylfluorosulfates. These in situ generated arylfluorosulfates are directly tested in a cancer-cell growth inhibition assay in parallel with their phenolic precursors. We discover three arylfluorosulfates that exhibit improved anticancer cell proliferation activities compared to their phenol precursors. Among these three compounds, the fluorosulfate derivative of Fulvestrant possesses significantly enhanced activity to down-regulate estrogen receptor (ER) expression in ER+ breast cancer cell line MCF-7 and the fluorosulfate derivative of Combretastatin A4-a general anticancer drug currently being evaluated under clinical trials-exhibits a 70-fold increase in potency in the drug resistant colon cancer cell line HT-29.

| S-EPMC6192542 | biostudies-literature

Aqueous Benzylic C-H Trifluoromethylation for Late-Stage Functionalization.

Project description:The installation of trifluoromethyl groups has become an essential step across a number of industries such as agrochemicals, drug discovery, and materials. Consequently, the rapid introduction of this critical functional group in a predictable fashion would benefit current practitioners in those fields. This communication describes a mild trifluoromethylation of benzylic C-H bonds with high selectivity for the least hindered hydrogen atom. The reaction provides monotrifluoromethylation and proceeds in an environmentally friendly acetone/water solvent system. The method can be used to install benzylic trifluoromethyl groups on highly functionalized drug molecules.

| S-EPMC6310231 | biostudies-literature

A Perspective on Late-Stage Aromatic C-H Bond Functionalization.

Project description:Late-stage functionalization of C-H bonds (C-H LSF) can provide a straightforward approach to the efficient synthesis of functionalized complex molecules. However, C-H LSF is challenging because the C-H bond must be functionalized in the presence of various other functional groups. In this Perspective, we evaluate aromatic C-H LSF on the basis of four criteria─reactivity, chemoselectivity, site-selectivity, and substrate scope─and provide our own views on current challenges as well as promising strategies and areas of growth going forward.

| S-EPMC8855345 | biostudies-literature

Photocatalytic Late-Stage Functionalization of Sulfonamides via Sulfonyl Radical Intermediates.

Project description:A plethora of drug molecules and agrochemicals contain the sulfonamide functional group. However, sulfonamides are seldom viewed as synthetically useful functional groups. To confront this limitation, a late-stage functionalization strategy is described, which allows sulfonamides to be converted to pivotal sulfonyl radical intermediates. This methodology exploits a metal-free photocatalytic approach to access radical chemistry, which is harnessed by combining pharmaceutically relevant sulfonamides with an assortment of alkene fragments. Additionally, the sulfinate anion can be readily obtained, further broadening the options for sulfonamide functionalization. Mechanistic studies suggest that energy-transfer catalysis (EnT) is in operation.

| S-EPMC9127806 | biostudies-literature

Ambient methane functionalization initiated by electrochemical oxidation of a vanadium (V)-oxo dimer.

Project description:The abundant yet widely distributed methane resources require efficient conversion of methane into liquid chemicals, whereas an ambient selective process with minimal infrastructure support remains to be demonstrated. Here we report selective electrochemical oxidation of CH4 to methyl bisulfate (CH3OSO3H) at ambient pressure and room temperature with a molecular catalyst of vanadium (V)-oxo dimer. This water-tolerant, earth-abundant catalyst possesses a low activation energy (10.8?kcal mol?1) and a high turnover frequency (483 and 1336?hr-1 at 1-bar and 3-bar pure CH4, respectively). The catalytic system electrochemically converts natural gas mixture into liquid products under ambient conditions over 240?h with a Faradaic efficiency of 90% and turnover numbers exceeding 100,000. This tentatively proposed mechanism is applicable to other d0 early transition metal species and represents a new scalable approach that helps mitigate the flaring or direct emission of natural gas at remote locations.

| S-EPMC7378254 | biostudies-literature

Manganese-catalysed benzylic C(sp3)-H amination for late-stage functionalization.

Project description:Reactions that directly install nitrogen into C-H bonds of complex molecules are significant because of their potential to change the chemical and biological properties of a given compound. Although selective intramolecular C-H amination reactions are known, achieving high levels of reactivity while maintaining excellent site selectivity and functional-group tolerance remains a challenge for intermolecular C-H amination. Here, we report a manganese perchlorophthalocyanine catalyst [MnIII(ClPc)] for intermolecular benzylic C-H amination of bioactive molecules and natural products that proceeds with unprecedented levels of reactivity and site selectivity. In the presence of a Brønsted or Lewis acid, the [MnIII(ClPc)]-catalysed C-H amination demonstrates unique tolerance for tertiary amine, pyridine and benzimidazole functionalities. Mechanistic studies suggest that C-H amination likely proceeds through an electrophilic metallonitrene intermediate via a stepwise pathway where C-H cleavage is the rate-determining step of the reaction. Collectively, these mechanistic features contrast with previous base-metal-catalysed C-H aminations and provide new opportunities for tunable selectivities.

| S-EPMC6217814 | biostudies-literature

Silanol: a bifunctional group for peptide synthesis and late-stage functionalization.

Project description:Chemical modification of a specific amino acid residue on peptides represents an efficient strategy to improve their pharmacokinetics and facilitates the potential to achieve post-synthetic diversification of peptides. Herein, we reported the first Pd-catalyzed late-stage ortho-olefination of Tyr residues on peptides with high chemo- and site-selectivity, by employing the easily attached and removable silanol as a bifunctional protecting group and directing group. Up to hexapeptides with variation on amino acid sequences or locations of the Tyr residue and different olefins were compatible with this protocol, which enriched the chemical toolbox for late-stage modification via C(sp2)-H functionalization. Furthermore, the orthogonal protection strategies of Tyr were also developed and could be applied to SPPS.

| S-EPMC8159358 | biostudies-literature

Anodic oxidation triggered divergent 1,2- and 1,4-group transfer reactions of β-hydroxycarboxylic acids enabled by electrochemical regulation.

Project description:We report a set of electrochemically regulated protocols for the divergent synthesis of ketones and β-keto esters from the same β-hydroxycarboxylic acid starting materials. Enabled by electrochemical control, the anodic oxidation of carboxylic acids proceeded in either a one-electron or a two-electron pathway, leading to a 1,4-aryl transfer or a semipinacol-type 1,2-group transfer product with excellent chemoselectivity. The 1,4-aryl transfer represents an unprecedented example of carbon-to-oxygen group transfer proceeding via a radical mechanism. In contrast to previously reported radical group transfer reactions, this 1,4-group transfer process features the migration of electron-rich aryl substituents. Furthermore, with these chemoselective electrochemical oxidation protocols, a range of ketones and β-keto esters including those possessing a challenging-to-access medium-sized ring could be synthesized in excellent yields.

| S-EPMC8162457 | 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