The sequencing of multicomponent reactions (MCRs) and subsequent cyclization is a powerful stratagem for the rapid synthesis diverse heterocyclic scaffolds. optimal MCR sufficiently flexible that it can be employed to generate adducts bearing variety functional groups may then selectively paired enable different manifolds, thereby leading collection products. growing interest in diversity-oriented has led increased attention this paradigm library synthesis, which inspired many advances...

Significance Of the many receptors that were pharmacologically described during 20th century, almost all cloned by end of 1990s. A key exception is σ 2 receptor, a potential therapeutic target for diseases as diverse schizophrenia, Alzheimer’s disease, and cancer. Despite development rich pharmacopeia, unknown molecular identity receptor has crippled biological investigation. Here, we identify TMEM97, membrane protein implicated in cancer binding partner Niemann–Pick disease NPC1. Our...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHigh enantioselectivity in the intramolecular cyclopropanation of allyl diazoacetates using a novel rhodium(II) catalystMichael P. Doyle, Roland J. Pieters, Stephen F. Martin, Richard E. Austin, Christopher Oalmann, and Paul MuellerCite this: Am. Chem. Soc. 1991, 113, 4, 1423–1424Publication Date (Print):February 1, 1991Publication History Published online1 May 2002Published inissue 1 February...

As a prelude to undertaking the total syntheses of complex manzamine alkaloids, series model studies were conducted establish scope and limitations intramolecular [4 + 2] cycloadditions N-acylated vinylogous ureas with trienic substrates 17a,b, 28a,b, 34. These experiments clearly demonstrated that geometry internal double bond presence an electron-withdrawing group on diene moiety essential for facile stereoselective formation desired cycloadducts. The enantioselective alkaloids ircinol A...

A four-component coupling process involving sequential reactions of aldehydes, primary amines, acid chlorides, and nucleophiles has been developed to prepare multifunctional substrates that may be employed in subsequent ring-forming generate a diverse array functionalized heterocyclic scaffolds. This new approach diversity-oriented synthesis was then applied the first total isopavine alkaloid (+/-)-roelactamine.

A novel bifunctional catalyst derived from BINOL has been developed that promotes the highly enantioselective bromolactonizations of a number structurally distinct unsaturated acids. Like some known catalysts, this 4- and 5-aryl-4-pentenoic acids, but it also catalyzes 5-alkyl-4(Z)-pentenoic These reactions represent first catalytic alkyl-substituted olefinic acids proceed via 5-exo mode cyclizations to give lactones in which new carbon-bromine bonds are formed at stereogenic center with...

Abstract One of the major challenges in contemporary synthetic organic chemistry is design and development new tactics strategies their application to concise efficient syntheses biologically active natural products. Strategies that utilize reactions enable rapid assembly skeletal framework such targets are thus especially attractive. In this context, we have developed novel applications imine Mannich related reactions, cascade processes, multicomponent (MCRs) rapidly assemble structural...

Succinate- and cyclopropane-derived phosphotyrosine (pY) replacements were incorporated into a series of Grb2 SH2 binding ligands wherein the pY+1 residue was varied to determine explicitly how variations in ligand preorganization affect energetics structure. The complexes these with domain examined thermodynamic structural investigations using isothermal titration calorimetry X-ray crystallography. enthalpies for all favorable, although entropies having hydrophobic at site those hydrophilic...

Accumulating evidence suggests that modulating the sigma 2 receptor (Sig2R) can provide beneficial effects for neurodegenerative diseases. Herein, we report identification of a novel class Sig2R ligands and their cellular in vivo activity experimental models Alzheimer's disease (AD). We SAS-0132 DKR-1051, selective Sig2R, modulate intracellular Ca2+ levels human SK-N-SH neuroblastoma cells. The JVW-1009 are neuroprotective C. elegans model amyloid precursor protein-mediated...

Neuropathic pain is an important medical problem with few effective treatments. The sigma 1 receptor (σ1R) known to be a potential target for neuropathic therapeutics, and antagonists this are in preclinical models currently phase II clinical trials. Conversely, relatively little about σ2R, which has recently been identified as transmembrane protein 97 (Tmem97). We generated series of σ1R σ2R/Tmem97 agonists tested them efficacy the mouse spared nerve injury (SNI) model. In agreement...

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTEnantioselective Total Syntheses of Ircinal A and Related Manzamine AlkaloidsStephen F. Martin, John M. Humphrey, Amjad Ali, Michael C. HillierView Author Information Department Chemistry Biochemistry The University Texas, Austin, TX 78712 Cite this: J. Am. Chem. Soc. 1999, 121, 4, 866–867Publication Date (Web):January 15, 1999Publication History Received14 August 1998Published online15 January 1999Published inissue 1 February...

A linear synthesis of the indole alkaloid (±)-akuammicine (2) was completed by a novel sequence reactions requiring only 10 steps from commercially available starting materials. The approach features tandem vinylogous Mannich addition and an intramolecular hetero Diels−Alder reaction to rapidly assemble pentacyclic heteroyohimboid derivative 8 readily hydrocarboline 6. Oxidation E ring gave lactone 9 that converted into deformylgeissoschizine (11). subsequent elaboration 11 2 effected...

The methodology for the preparation of aldehydes, ketones, and carboxylic acids or their derivatives from lower carbonyl compounds by carbon-carbon bond forming reactions is reviewed. material presented according to number carbon atoms (1, 2, 3, 4) that separate acyl group, added during formation, original electrophilic center. 1. Introduction 2. Aldehydes Ketones One Carbon Elongations 2.1. Addition Masked Acyl Anions 2.2. Reductive Nucleophilic Acylation 2.3. Followed Additional Carbonyl...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTGeneral strategies for the synthesis of indole alkaloids. Total (.+-.)-reserpine and (.+-.)-.alpha.-yohimbineStephen F. Martin, Heinrich Rueger, Sidney A. Williamson, Slawek GrzejszczakCite this: J. Am. Chem. Soc. 1987, 109, 20, 6124–6134Publication Date (Print):September 1, 1987Publication History Published online1 May 2002Published inissue 1 September...

A substituted heterocyclic scaffold comprising a 1,4-benzodiazepine fused with 1,2,3-triazole ring has been synthesized and diversified via variety of refunctionalizations. The strategy features the rapid assembly by combining 3−4 reactants in an efficient multicomponent process, followed intramolecular Huisgen cycloaddition.

A mild and general protocol for the carbonylative cross-coupling of sterically hindered ortho-disubstituted aryl iodides is reported. Carbonylative Suzuki−Miyaura couplings a variety boronic acids provide an array substituted biaryl ketones in modest to excellent yield. Negishi coupling that utilizes alkynyl nucleophiles also described.

The first enantioselective total synthesis of (-)-citrinadin A has been accomplished in 20 steps from commercially available materials via an approach that minimizes refunctionalization and protection/deprotection operations. cornerstone this features asymmetric vinylogous Mannich addition a dienolate to chiral pyridinium salt set the initial center. sequence substrate-controlled reactions, including highly stereoselective epoxidation/ring-opening oxidative rearrangement indole furnish...