Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD) is a well-characterized model of human multiple sclerosis (MS) that closely resembles the chronic and progressive clinical form disease. Recent studies have described involvement cannabinoid system in progression benefits associated with administration agonists. With objective to study whether "indirect" agonists, is, compounds able reinforce physiological endocannabinoid transmission and, therefore, devoid...

Herein, we describe the catalytic enantioselective cross-coupling of 1,2-bisboronic esters. Prior work on group specific cross coupling is limited to use geminal bis-boronates. This desymmetrization provides a novel approach prepare enantioenriched cyclopropyl boronates with three contiguous stereocenters, that could be further derivatized through selective functionalization carbon-boron bond. Our results suggest transmetallation, which enantiodetermining step, takes place retention...

Selective functionalization of the C–B bond in 1,2-bis(boronate) esters has emerged as a powerful tool to prepare 1,2-difunctionalized compounds with stereocontrol. Suzuki cross-coupling, oxidation, amination, and homologation reactions serve platforms wide variety from common intermediate. The exquisite selectivity offered their easy preparation feedstock material using myriad catalytic transformations make them attractive building blocks for complex molecules. In this Perspective, we...

The cellular inactivation of the endogenous cannabinoid (endocannabinoid) anandamide (AEA) represents a controversial and intensely investigated subject. This process has been proposed to involve two proteins, transporter that promotes uptake AEA fatty acid amide hydrolase (FAAH), which hydrolyzes arachidonic acid. However, whereas role FAAH in metabolism is well-characterized, identity putative remains enigmatic. Indeed, indirect pharmacological evidence used support existence an suggested...

A new series of arachidonic acid derivatives were synthesized and evaluated as inhibitors the endocannabinoid uptake. Most them are able to inhibit anandamide uptake with IC50 values in low micromolar range (IC50 = 0.8−24 μM). In general, compounds had only weak effects upon CB1, CB2, VR1 receptors (Ki > 1000−10000 nM). addition, there was no obvious relationship between abilities affect metabolism by fatty amidohydrolase (FAAH; 30−113 This indicates that do not exert their secondarily FAAH...

Gold mesoionic carbenes having a chiral sulfoxide group attached to the C4 position of five membered ring have been prepared and tested as catalysts in cycloisomerization enynes. These new are very efficient, with moiety playing key role their activity N1-substituent control regioselectivity these processes.

In the present work, we have designed and synthesized a series of arachidonic acid derivatives general structure I which been characterized as highly potent selective inhibitors anandamide transporter (IC50 = 24−0.8 μM, Ki > 1000−5000 nM for CB1 CB2 cannabinoid receptors vanilloid VR1 receptor). Among them, N-(3-furylmethyl)eicosa-5,8,11,14-tetraenamide deserves special attention being most endocannabinoid inhibitor 0.8 μM) described to date.

A new procedure for the asymmetric synthesis of imidazolidines and vicinal diamines is reported. The 1,3-dipolar cycloaddition between nonracemic p-tolylsulfinimines azomethine ylides generated in situ from alpha-iminoesters LDA produces N-sulfinylimidazolidines with a high degree stereocontrol. In contrast, presence Lewis acids promotes formation cycloadducts through highly diastereoselective process opposite stereochemistry. Subsequent transformations including oxidative, reductive,...

We have designed and synthesized a new series of arylpiperazines V exhibiting high 5-HT1AR affinity selectivity over α1-adrenoceptors. The selective ligands contain hydantoin (m = 0) or diketopiperazine 1) moiety an arylpiperazine separated by one methylene unit (n 1). aryl substituent the piperazine (Ar) consists different benzofused rings mimicking favorable voluminous substituents at ortho meta positions predicted 3D-QSAR analysis in previously reported I. In particular,...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTKinetic resolution of racemic disubstituted 1-pyrrolines via asymmetric reduction with a chiral titanocene catalystAlma Viso, Nancy E. Lee, and Stephen L. BuchwaldCite this: J. Am. Chem. Soc. 1994, 116, 20, 9373–9374Publication Date (Print):October 1, 1994Publication History Published online1 May 2002Published inissue 1 October 1994https://pubs.acs.org/doi/10.1021/ja00099a082https://doi.org/10.1021/ja00099a082research-articleACS PublicationsRequest...

The diastereoselective addition of lithiated vinyl sulfoxides to enantiopure sulfinimines provides direct access a wide assortment allylic sulfinamides in good yields and excellent selectivities. These adducts are key precursors differently functionalized cis- trans-dihydropyrroles. Modulation the protecting group on nitrogen prior cyclization has significant impact stereochemical outcome, allowing for selective preparation 2,5-cis- or 2,5-trans-3-sulfinyl disubstituted dihydropyrroles from...

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTSulfur-Directed Asymmetric 1,3-Dipolar Cycloadditions of Azomethine Ylides with Enantiopure Sulfinimines†,‡Alma Viso, Roberto Fernández de la Pradilla, Carlos Guerrero-Strachan, Marta Alonso, Martín Martínez-Ripoll, and Isabelle AndréView Author Information Departamento Química Orgánica I, Facultad Química, Universidad Complutense, E-28040 Madrid, Spain, Instituto Orgánica, CSIC, Juan Cierva, 3, E-28006 Cristalografía, Química-Física...

A survey of routes for aminal cleavage N-sulfinylimidazolidines has been carried out, and selective conditions to cleave the moiety while preserving sulfinamide group unaltered have found. Thus, treatment enantiopure with aqueous H3PO4 in THF affords N-sulfinyldiamino esters excellent yields, presence MeOH as cosolvent allows simultaneous removal cleavage. The behavior these substrates a variety chemical transformations explored.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStrain-directed bridge cleavage of (phenylsulfonyl)-7-oxabicyclo[2.2.1]heptane derivatives: application to the total synthesis carba-.alpha.-DL-glucopyranoseJose Luis Acena, Odon Arjona, Roberto Fernandez de la Pradilla, Joaquin Plumet, and Alma VisoCite this: J. Org. Chem. 1992, 57, 7, 1945–1946Publication Date (Print):March 1, 1992Publication History Published online1 May 2002Published inissue 1 March...

The response of anandamide is terminated by a carrier‐mediated transport followed degradation catalyzed the cloned enzyme fatty acid amidohydrolase (FAAH). In this study, we provide biochemical data showing an uptake process and expression FAAH in human prostate. Anandamide was accumulated PC‐3 cells saturable temperature‐dependent process. Kinetic studies uptake, determined presence cannabinoid vanilloid antagonists, revealed apparent parameters K M =4.7±0.2 μ V max =3.3±0.3 pmol min −1 (10...

Enantiopure 1-benzyl-2,3-disubstituted piperazines (4) have been synthesized by treatment of N-sulfinyl-N-benzyldiamino alcohols (1) with diethyl oxalate and sodium methoxide followed reduction borane. Alternatively, the sulfinamido group was preserved an N-acylation/cyclization protocol using α-chloroacetyl chloride that led to synthesis N-sulfinyl ketopiperazines (11). Ensuing elimination sulfinyl NaH produced imino (9) are suitably functionalized for nucleophilic addition moiety....

The addition of enantiopure α-metalated vinyl and dienyl sulfoxides to enantiomerically pure N-sulfinimines takes place with high diastereoselectivity primarily directed by the N-sulfinimine sulfur. resulting allylic amines have been further transformed into highly functionalized 3-sulfinyl 3-sulfonyl 2,5-cis-dihydropyrroles reaction electrophiles.

The [2,3]-sigmatropic rearrangement of a variety configurationally stable diastereomeric allylic sulfinyl dihydropyrans, produced by base-promoted cyclization dienols, has been studied. In some cases, the efficient transformation these substrates into dihydropyranols required an in-depth study reaction conditions, with preferred protocol relying on use DABCO in warm toluene. This methodology applied to syntheses cores ent-dysiherbaine and deoxymalayamicin A means tethered aminohydroxylations.

The highly selective base-promoted cyclization of enantiopure sulfinyl dienols affords allylic dihydropyrans. scope this methodology, including the preparation seven-membered rings, has been studied in depth. reactivity our dihydropyrans toward oxidation, imination, and dihydroxylation explored, thus several routes to densely functionalized pyran derivatives have outlined. dihydropyranyl sulfones sulfoximines SN2′ processes with organocuprates examined. displacement products were obtained...