Enantioselective Nucleophilic Vinylic Substitution of Nitroolefins for the Synthesis of 3-Alkenyl Oxindoles.

An asymmetric catalytic nucleophilic vinylic substitution (SV) reaction of 5-thiazol-4-ones and nitroolefins has been developed for the synthesis of 3-alkenyl oxindoles. The enantioselective SV reaction with a nitro group as the leaving group proceeded smoothly to afford 3-alkenyl oxindoles in good yields with high regio- and enantioselectivity. The reaction showed broad substrate applicability.

Synthesis of Pyrimido[1,2-]indolediones and Pyrimidinediones via [4+2] Annulation of 2-Azirine-2-carbaldehydes.

NHC-catalyzed [4+2] annulation of 2-azirine-2-carbaldehydes with ketimines and isocyanates has been developed, providing straightforward synthetic protocols for constructing structurally intriguing pyrimido[1,2-]indolediones and pyrimidinediones under mild conditions with excellent yields. This protocol can be used to synthesize the core skeleton of pharmaceutically important drugs and pyrimido[1,2-]indoledione-containing natural products, making it potentially valuable for creating biologically active derivatives.

Desymmetric [3+3] Cyclization of -Quinamines for the Synthesis of 1,2,4-Oxadiazines and Hydroquinoxalines.

General and efficient strategies for highly diastereoselective synthesis of divergent heterocyclic scaffolds through desymmetric [3+3] cycloaddition of -quinamines with 1,3-dipole surrogates hydroximoyl halides and α-halohydroxamates have been developed. This synthetic protocol provided a variety of heterocyclic architectures containing 1,2,4-oxadiazine and hydroquinoxaline skeletons in good yields with a wide substrate scope.

Origin, structure and functional transition of sex pheromone components in a false widow spider.

Female web-building spiders disseminate pheromone from their webs that attracts mate-seeking males and deposit contact pheromone on their webs that induces courtship by males upon arrival. The source of contact and mate attractant pheromone components, and the potential ability of females to adjust their web's attractiveness, have remained elusive. Here, we report three new contact pheromone components produced by female false black widow spiders, Steatoda grossa: N-4-methylvaleroyl-O-butyroyl-L-serine, N-4-methylvaleroyl-O-isobutyroyl-L-serine and N-4-methylvaleroyl-O-hexanoyl-L-serine.

Organocatalytic Asymmetric Synthesis of Tetrahydroquinolines from -Aminophenyl -Quinone Methides.

The asymmetric catalytic [4 + 2] cycloannulation of -aminophenyl -QMs with different types of alkenes for the construction of tetrahydroquinolines containing three contiguous stereogenic centers was developed. This is the first example of catalytic asymmetric cycloannulation of -aminophenyl -QMs. This reaction exhibits excellent functional group tolerance.

Asymmetric α-Regioselective [3 + 2] Annulation of Morita-Baylis-Hillman Carbonates: Construction of Three Contiguous Stereocenters with Vicinal Quaternary Carbon Centers.

Asymmetric α-regioselective annulation of MBH carbonates with 4-arylmethylisoxazol-5-ones has been developed to afford spirocyclic oxindole derivatives containing three contiguous stereogenic centers and vicinal all-carbon quaternary chiral centers. This reaction exhibits a broad substrate scope and excellent functional group tolerance. Excellent yields with high diastereo- and enantioselectivities were obtained in this efficient organocatalytic reaction.

Diversity-oriented synthesis of glycomimetics.

Glycomimetics are structural mimics of naturally occurring carbohydrates and represent important therapeutic leads in several disease treatments. However, the structural and stereochemical complexity inherent to glycomimetics often challenges medicinal chemistry efforts and is incompatible with diversity-oriented synthesis approaches. Here, we describe a one-pot proline-catalyzed aldehyde α-functionalization/aldol reaction that produces an array of stereochemically well-defined glycomimetic building blocks containing fluoro, chloro, bromo, trifluoromethylthio and azodicarboxylate functional groups.

A Sentence-Level Joint Relation Classification Model Based on Reinforcement Learning.

Relation classification is an important semantic processing task in the field of natural language processing (NLP). Data sources generally adopt remote monitoring strategies to automatically generate large-scale training data, which inevitably causes label noise problems. At the same time, another challenge is that important information can appear at any place in the sentence.

Glycoside hydrolase stabilization of transition state charge: new directions for inhibitor design.

Carbasugars are structural mimics of naturally occurring carbohydrates that can interact with and inhibit enzymes involved in carbohydrate processing. In particular, carbasugars have attracted attention as inhibitors of glycoside hydrolases (GHs) and as therapeutic leads in several disease areas. However, it is unclear how the carbasugars are recognized and processed by GHs.

Isolation, Structure Elucidation, and Total Synthesis of Dolichovespulide, a Sesquiterpene from Yellowjackets.

As part of an ongoing program to identify sex attractant pheromone components that mediate sexual communication in yellowjacket wasps, a novel sesquiterpene was isolated from body surface extracts of virgin bald-faced hornet queens, . The gross structure of this sesquiterpene was proposed through microscale spectroscopic analyses, and the configuration of the central olefin was subsequently confirmed by total synthesis. This new natural product (termed here dolichovespulide) represents an important addition to the relatively small number of terpenoids reported from the taxonomic insect family Vespidae.

Author Correction: Revealing the mechanism for covalent inhibition of glycoside hydrolases by carbasugars at an atomic level.

In the originally published version of this Article, the affiliation details for Tracey M. Gloster were incorrectly given as 'Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada'. The correct affiliation is 'Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK'.

Revealing the mechanism for covalent inhibition of glycoside hydrolases by carbasugars at an atomic level.

Mechanism-based glycoside hydrolase inhibitors are carbohydrate analogs that mimic the natural substrate's structure. Their covalent bond formation with the glycoside hydrolase makes these compounds excellent tools for chemical biology and potential drug candidates. Here we report the synthesis of cyclohexene-based α-galactopyranoside mimics and the kinetic and structural characterization of their inhibitory activity toward an α-galactosidase from Thermotoga maritima (TmGalA).

Maculatic Acids-Sex Attractant Pheromone Components of Bald-Faced Hornets.

Yellowjackets in the genera Vespula and Dolichovespula are prevalent eusocial insects of great ecological and economic significance, but the chemical signals of their sexual communication systems have defied structural elucidation. Herein, we report the identification of sex attractant pheromone components of virgin bald-faced hornet queens (Dolichovespula maculata). We analyzed body surface extracts of queens by coupled gas chromatographic-electroantennographic detection (GC-EAD), isolated the compounds that elicited responses from male antennae by high-performance liquid chromatography (HPLC), and identified these components by GC mass spectrometry (MS), HPLC-MS, and NMR spectroscopy.

Total Synthesis of (±)-Strictamine.

The total synthesis of strictamine has been achieved in nine steps from a known enol triflate. Characteristic features of our approach included: a) creation of a C7 all-carbon quaternary stereocenter at an early synthetic stage; b) use of an N,N-dimethyl tertiary amine as a surrogate of the primary amine for the rapid build-up of a functionalized 2-azabicyclo[3,3,1]nonan-9-one skeleton (achieved by using a reaction sequence of α-bromination of the ketone, followed by a stereoconvergent intramolecular nucleophilic substitution reaction); and c) a late-stage construction of the indolenine unit.

Total synthesis of (±)-aspidophylline A.

A total synthesis of aspidophylline A, a pentacyclic akuammiline-type monoterpene indole alkaloid, is described. The synthesis features: 1) rapid access to a fully functionalized dihydrocarbazole through the desymmetrization of readily available 2-allyl-2-(o-nitrophenyl)cyclohexane-1,3-dione; 2) an intramolecular azidoalkoxylation of an enecarbamate to install both the furoindoline ring and the azido functionality; and 3) an intramolecular Michael addition for the construction of the 2-azabicyclo[3.3.

Automatic salient object detection via maximum entropy estimation.

This Letter proposes a rapid method for automatic salient object detection inspired by the idea that an image consists of redundant information and novelty fluctuations. We believe object detection can be achieved by removing the nonsalient parts and focusing on the salient object. Considering the relation between the composition of the image and the aim of object detection, we constructed what we believe is a more reliable saliency map to evaluate the image composition.

Diastereoselective total synthesis of (±)-schindilactone a, Part 3: The final phase and completion.

The final phase for the total synthesis of (±)-schindilactone A (1) is described herein. Two independent synthetic approaches were developed that featured Pd-thiourea-catalyzed cascade carbonylative annulation reactions to construct intermediate 3 and a RCM reaction to make intermediate 4. Other important steps that enabled the completion of the synthesis included: 1) A Ag-mediated ring-expansion reaction to form vinyl bromide 17 from dibromocyclopropane 30; 2) a Pd-catalyzed coupling reaction of vinyl bromide 17 with a copper enolate to synthesize ketoester 16; 3) a RCM reaction to generate oxabicyclononenol 10 from diene 11; 4) a cyclopentenone fragment in substrate 8 was constructed through a Co-thiourea-catalyzed Pauson-Khand reaction (PKR); 5) a Dieckmann-type condensation to successfully form the A ring of schindilactone A (1).

Diastereoselective total synthesis of (±)-schindilactone A, Part 2: Construction of the fully functionalized CDEFGH ring system.

The successful synthesis of the highly complex model compound (2) of the CEFGH ring system of schindilactone A (1) is described. Several synthetic methodologies were developed and applied to achieve this goal, including ring-closing metathesis (RCM) and Co-thiourea-catalyzed Pauson-Khand reactions. Furthermore, two independent approaches were developed for the construction of the GH ring of model compound 2, the key steps of which included Pd-thiourea-catalyzed carbonylative annulation, methylation, and sequential RCM/oxa-Michael-addition reactions.

Diastereoselective total synthesis of (±)-schindilactone A, Part 1: Construction of the ABC and FGH ring systems and initial attempts to construct the CDEF ring system.

First-generation synthetic strategies for the diastereoselective total synthesis of schindilactone A (1) are presented and methods for the synthesis of the ABC, FGH, and CDEF moieties are explored. We have established a method for the synthesis of the ABC moiety, which included both a Diels-Alder reaction and a ring-closing metathesis as the key steps. We have also developed a method for the synthesis of the FGH moiety, which involved the use of a Pauson-Khand reaction and a carbonylative annulation reaction as the key steps.

Enantioselective and collective syntheses of xanthanolides involving a controllable dyotropic rearrangement of cis-β-lactones.

Let's swap: a scalable, atom-economic, enantio-, and diastereoselective synthetic route to trisubstituted γ-butyrolactones based on a Wagner-Meerwein-type dyotropic rearrangement of cis-β-lactones is described. This methodology was applied in efficient and protecting-group-free formal syntheses and total syntheses of various xanthanolide natural products.

Stereoselective construction of an unprecedented 7-8 fused ring system in micrandilactone a by [3,3]-sigmatropic rearrangement.

The 7-8 bicyclic ring system of micrandilactone A (1) with the required stereochemistry and functional groups was constructed by a Bu3Al-promoted Claisen rearrangement. Computational studies indicated that the exocyclic vinyl ether undergoes a [3,3] sigmatropic process via a chairlike transition state to afford exclusively the Z-double bond in the newly generated 8-membered ring with a high level of chirality transfer.