Erick M Carreira

ETH Zurich | ETH Zürich

The involvement of planar carbocation intermediates is generally considered undesirable in asymmetric catalysis due to the difficulty in gaining facial control and their intrinsic stability issues. Recently, suitably designed chiral catalyst(s) have enabled a guided approach of nucleophiles to one of the prochiral faces of carbocations affording hi...

Intermolecular cyclopropanation of mono-, di-, and trisubstituted olefins with α-bromo-β-ketoesters and α-bromomalonates under organophotocatalysis is reported. The reaction displays broad functional group tolerance, including substrates bearing acids, alcohols, halides, ethers, ketones, nitriles, esters, amides, carbamates, silanes, stannanes, bor...

Pharmacological modulation of cannabinoid receptor type 2 (CB2R) holds promise for the treatment of neuroinflammatory disorders, such as Alzheimer’s disease. Despite the importance of CB2R, its expression and downstream signaling are insufficiently understood in disease- and tissue-specific con-texts. Ligand-directed covalent (LDC) labeling enables...

The molecular and crystal structures of 19 N‐alkyl‐substituted pipecolamide derivatives with partial fluorination of N‐propyl and N‐butyl groups are presented. Fluorination patterns include one fluorine atom at internal or terminal locations, two fluorine atoms in geminal or vicinal arrangements at various positions, as well as terminal trifluorome...

Host-associated bacteria are increasingly being recognized as underexplored sources of bioactive natural products with unprecedented chemical scaffolds. A recently identified example is the plant-root-associated marine bacterium Gynuella sunshinyii of the chemically underexplored order Oceanospirillales. Its genome contains at least 22 biosynthetic...

Labeled chemical probes are of utmost importance to bring drugs from the laboratory through the clinic and ultimately to market. They support and impact all research and discovery phases: target verification and validation; assay development; lead optimization; and biomarker engagement in the context of preclinical studies and human trials. Probes...

The cycloisomerization of β-, γ-, and δ-unsaturated N-acyl sulfonamides to N-sulfonyl lactams and imidates is reported. This transformation is effected in the presence of a CoIII(salen) catalyst using t-BuOOH or air as the oxidant. The method shows good functional group tolerance (alkyl, aryl, heteroaryl, ether, N-Boc) and furnishes an underexplore...

The distribution and roles of the cannabinoid CB2 receptor in the CNS are still a matter of debate. Recent data suggest that, in addition to its presence in microglial cells, the CB2 receptor may be also expressed at low levels, yet biologically relevant, in other cell types such as neurons. It is accepted that the expression of CB2 receptors in th...

Aging is impacted by interventions across species, often converging on metabolic pathways. Transcription factors regulate longevity yet approaches for their pharmacological modulation to exert geroprotection remain sparse. We show that increased expression of the transcription factor Grainyhead 1 (GRH-1) promotes lifespan and pathogen resistance in...

The molecular nanoscale organization of the surfaceome is a fundamental regulator of cellular signaling in health and disease. Technologies for mapping the spatial relationships of cell surface receptors and their extracellular signaling synapses would unlock theranostic opportunities to target protein communities and the possibility to engineer ex...

We report a modular approach toward novel arylazotriazole photoswitches and their photophysical characterization. Addition of lithiated TIPS-acetylene to aryldiazonium tetrafluoroborate salts gives a wide range of azoacetylenes, constituting an underexplored class of stable intermediates. In situ desilylation transiently leads to terminal arylazoac...

The cis-stereoisomers of Δ⁹-THC [(−)-3 and (+)-3] were identified and quantified in a series of low-THC-containing varieties of Cannabis sativa registered in Europe as fiber hemp and in research accessions of cannabis. While Δ⁹-cis-THC (3) occurs in cannabis fiber hemp in the concentration range of (−)-Δ⁹-trans-THC [(−)-1], it was undetectable in a...

A method for the enantio- and chemoselective iridium-catalyzed O-allylation of oximes is described. Kinetic resolution in an intramolecular setting provides enantioenriched oxime ethers and aliphatic allylic alcohols. The synthetic potential of the products generated with this method is showcased by their elaboration into a series of heterocyclic c...

Enantioselective bond formation between sterically hindered fragments to furnish acyclic products with vicinal quaternary centers is a formidable challenge. We report a solution that involves cocatalysis between a chiral Ir-(phosphoramidite,olefin) complex and La(OTf)3. This robust catalytic system effects highly enantioconvergent and regioselectiv...

Cannabinoid receptor 2 (CB2) is a promising target for the treatment of neuroinflammation and other diseases. However, a lack of understanding of its complex signaling in cells and tissues complicates the therapeutic exploitation of CB2 as a drug target. We show for the first time that benchmark CB2 agonist HU308 increases cytosolic Ca2+ levels in...

Saturated heterocycles are very common motifs in numerous natural products and biologically active molecules. This chapter outlines various asymmetric approaches to piperidines. It focuses on catalytic, enantioselective methods that assemble piperidines from achiral or racemic building blocks. The chapter provides an overview of desymmetrization re...

A highly enantioselective and diastereoselective total synthesis of the diterpenoid (-)-mitrephorone A is presented. Key to the synthesis are stereocontrolled 1,4-semihydrogenation of a 1,3-diene to a tetrasubstituted double bond, enzyme-catalyzed malonate desymmetrization, and highly diastereoselective nitrile oxide cycloaddition. The streamlined...

Pharmacological modulation of cannabinoid type 2 receptor (CB2R) holds promise for the treatment of numerous con-ditions, including inflammatory diseases, autoimmune disorders, pain, and cancer. Despite the significance of this re-ceptor, researchers lack reliable tools to address questions concerning the expression and complex mechanism of CB2R si...

Delineating the molecular nanoscale organization of the surfaceome is pre-requisite for understanding cellular signaling. Technologies for mapping the spatial relationships of cell surface receptors and their extracellular signaling synapses would open up theranostic opportunities and the possibility to engineer extracellular signaling. Here, we de...

Controlling inflammation is critical for preventing many diseases including cancer, autoimmune disorders and hypersensitivity reactions. NF-E2-related factor 2 (Nrf2) is a key transcription factor that controls the cellular antioxidant and cytoprotective response. Moreover, Nrf2 has been implicated in the regulation of inflammatory processes, altho...

Serendipity has played a role in many groundbreaking scientific discoveries. Key to their identification and exploitation is the ability to recognize the unexpected and invest time trying to understand it. Like any other field of scientific research, total synthesis requires determination and perseverance. When the first-generation route towards a...

Oxidized lipids play a critical role in a variety of diseases with two faces: pro- and anti-inflammatory. The molecular mechanisms of this Janus-faced activity remain largely unknown. Here, we have identified that cyclopentenone-containing prostaglandins such as 15d-PGJ2 and structurally related oxidized phospholipid species possess a dual and oppo...

The enantioselective α-allylation of aqueous solutions of acetaldehyde using iridium- and amine-catalyzed substitution of racemic allylic alcohols is described. The method utilizes a readily available, safely handled aqueous solution of acetaldehyde and furnishes γ,δ-unsaturated aldehydes in good yields and greater than 99% enantiomeric excess. The...

The endocannabinoid (eCB) system is implied in various human diseases ranging from central nervous system to autoimmune disorders. Cannabinoid receptor 2 (CB2R) is an integral component of the eCB system. Yet, the downstream effects elicited by this G protein‐coupled receptor upon binding of endogenous or synthetic ligands are insufficiently unders...

Cannabinoid type 2 receptor (CB₂R) is a fundamental part of the endocannabinoid signaling system (eCB system), and is known to play an important role in tissue injury, inflammation, cancer and pain. In stark contrast to its significance, the underlying signaling mechanisms and tissue expression profiles are poorly understood. Due to its...

Cannabinoid type 2 receptor (CB 2 R) is a fundamental part of the endocannabinoid signaling system (eCB system), and is known to play an important role in tissue injury, inflammation, cancer and pain. In stark contrast to its significance, the underlying signaling mechanisms and tissue expression profiles are poorly understood. Due to its low expre...

Pharmacological modulation of cannabinoid type 2 receptor (CB2R) holds promise for the treatment of numerous conditions including inflammatory diseases, autoimmune disorders, pain, and cancer. Despite its significance, researchers lack reliable tools to address questions concerning the complex mechanism of CB2R signaling and its downstream conseque...

The enantioselective addition of a metal acetylide to a carbonyl compound, known as the enantioselective Favorskii reaction, is a versatile method for the construction of enantiomerically enriched propargylic alcohols. The scope of this reaction is broad in terms of both the alkyne and the carbonyl compound employed, and under appropriate condition...

Enantioselective synthesis of a highly versatile building block en route to trachylobanes and related terpenoids is presented. The synthesis features diastereoselective Diels-Alder cycloaddition reaction, a cyclopropanation/homoquadricyclane rearrangement cascade, and palladium-catalyzed C-H acetoxylation. The targeted tricyclooctane was obtained i...

In this Review, we highlight recent advances in the understanding and design of N‐functionalized pyridinium scaffolds as single electron, redox‐triggered functional group transfer reagents. We provide a selection of representative methods that demonstrate reactivity and fundamental advances in this emerging field. Reactivity of these reagents can b...

The endocannabinoid (eCB) system is implied in various human diseases ranging from central nervous system to autoimmune disorders. Cannabinoid receptor 2 (CB₂R) is an integral component of the eCB system. Yet, the downstream effects elicited by this G protein-coupled receptor upon binding of endogenous or synthetic ligands are insufficie...

In this Review, we highlight recent advances in the understanding and design of N‐functionalized pyridinium scaffolds as single electron, redox‐triggered functional group transfer reagents. We provide a selection of representative methods that demonstrate reactivity and fundamental advances in this emerging field. Reactivity of these reagents can b...

Optically active 1,3-enyne aldehydes undergo stereoselective, Au-catalyzed conversion to bicyclo[3.3.0]octenones (up to 97% ee, good d.r.) via a domino sequence involving 1,3-acyloxy migration, Nazarov cyclization and an unprecedented aldol addition.

The iridium-catalyzed asymmetric allylic substitution under biphasic conditions is reported. This approach allows the use of various unstable and/or volatile nucleophiles including hydrazines, methyl-amine, t-butyl hydroperoxide, N-hydroxylamine, α-chloroacetaldehyde and glutaraldehyde. This transformation pro-vides rapid access to a broad range of...

The catalytic, asymmetric synthesis of complex molecules has been a core focus of our research program for some time because developments in the area can have an immediate impact on the identification of novel strategies for the synthesis of value-added molecules. In concert with this central interest, we have emphasized the design of ligand scaffo...

Stereoselective synthesis of bicyclo[3.3.0]octenones from chiral 1,3 enyne aldehydes bearing propargylic acetates is described. The method is based on a Au(I)-catalyzed domino sequence with concomitant transfer of chirality involving 1,3-acyloxy migration followed by Nazarov cyclization and an unprecedented aldol addition. The method furnishes dens...

A palladium-catalyzed C–H iodination of unactivated alkenes is reported. A picolinamide directing group enables the regioselec-tive functionalization of a wide array of olefins to furnish io-dination products as single stereoisomers. Mechanistic investiga-tions suggest the reversible formation of a six-membered alkenyl palladacycle intermediate thr...