Flavone‐3′‐sulfon­amide

In the title mol­ecule, C₁₅H₁₁NO₄S, the phenyl and benzene rings are quite planar, with maximum deviations from planarity of 0.009 (2) and 0.004 (1) Å, respectively. The γ‐pyrone ring deviates from planarity and makes a dihedral angle of 8.3 (3)° with the 2‐phenyl substituent. The sulfon­amide group is involved in N—H?O hydrogen bonding.     

Artificial β‐Double Helices from Achiral γ‐Peptides

Double helices are not common in polypeptides and proteins except in the peptide antibiotic gramicidin A and analogous l,d ‐peptides. In contrast to natural polypeptides, remarkable β‐double‐helical structures from achiral γ‐peptides built from α,β‐unsaturated γ‐amino acids have been observed. The crystal structures suggest that they adopted parallel β‐double helical structures and these structures are stabilized by the interstrand backbone amide H‐bonds. Furthermore, both NMR spectroscopy and fluorescence studies support the existence of double‐helical conformations in solution. Although a variety of folded architectures featuring distinct H‐bonds have been discovered from the β‐ and γ‐peptide foldamers, this is the first report to show that achiral γ‐peptides can spontaneously intertwine into β‐double helical structures.     

α‐Aminoxy‐Acid‐Auxiliary‐Enabled Intermolecular Radical γ‐C(sp3)−H Functionalization of Ketones

A method for site‐specific intermolecular γ‐C(sp³)?H functionalization of ketones has been developed using an α‐aminoxy acid auxiliary applying photoredox catalysis. Regioselective activation of an inert C?H bond is achieved by 1,5‐hydrogen atom abstraction by an oxidatively generated iminyl radical. Tertiary and secondary C‐radicals thus formed at the γ‐position of the imine functionality undergo radical conjugate addition to various Michael acceptors to provide, after reduction and imine hydrolysis, the corresponding γ‐functionalized ketones.     

Direct Catalytic Asymmetric Mannich‐type Reaction of α,β‐Unsaturated γ‐Butyrolactam with Ketimines

We report a direct catalytic asymmetric Mannich‐type addition of α,β‐unsaturated γ‐butyrolactam to α‐ethoxycarbonyl ketimines promoted by a soft Lewis acid/Brønsted base cooperative catalyst. A thiophosphinoyl group on the nitrogen of ketimines was crucial for both electrophilic activation and α‐addition of γ‐butyrolactams. The obtained aza‐Morita–Baylis–Hillman‐type products bear an α‐amino acid architecture with a tetra‐substituted stereogenic center.     

Palladium‐Catalyzed Cascade Annulation To Construct Functionalized β‐ and γ‐Lactones in Ionic Liquids

A highly efficient and mild palladium‐catalyzed, one‐pot, four‐step cascade annulation has been developed to afford functionalized β‐ and γ‐lactones in moderate to good yields with high regio‐ and diastereoselectivities in ionic liquids. The employment of ionic liquids under mild reaction conditions makes this transformation green and practical. Especially, this reaction provided a novel and convenient methodology for the construction of naturally occurring biologically active β‐ and γ‐lactones.     

Two‐Step Synthesis of Multifunctional γ‐Lactams from γ‐Lactone

We present herein an efficient and rapid method for the synthesis of N,1‐dialkyl‐4‐(2‐hydroxyethyl)‐5‐oxopyrrolidine‐3‐carboxamides based on the conversion of γ‐lactone to γ‐lactam via the conjugate addition of primary amines to an ethyl α‐functionalized acrylate followed by intramolecular cyclization.     

Phosphine‐Catalyzed Enantioselective γ‐Addition of 3‐Substituted Oxindoles to 2,3‐Butadienoates and 2‐Butynoates: Use of Prochiral Nucleophiles

The first phosphine‐catalyzed enantioselective γ‐addition with prochiral nucleophiles and 2,3‐butadienoates as the reaction partners has been developed. Both 3‐alkyl‐ and 3‐aryl‐substituted oxindoles could be employed in this process, which is catalyzed by a chiral phosphine that is derived from an amino acid, thus affording oxindoles that bear an all‐carbon quaternary center at the 3‐position in high yields and excellent enantioselectivity. The synthetic value of these γ‐addition products was demonstrated by the formal total synthesis of two natural products and by the preparation of biologically relevant molecules and structural scaffolds.     

Understanding the Effect Models of Ionic Liquids in the Synthesis of NH4‐Dw and γ‐AlOOH Nanostructures and Their Conversion into Porous γ‐Al2O3

Well‐dispersed ammonium aluminum carbonate hydroxide (NH₄‐Dw) and γ‐AlOOH nanostructures with controlled morphologies have been synthesized by employing an ionic‐liquid‐assisted hydrothermal process. The basic strategies that were used in this work were: 1) A controllable phase transition from NH₄‐Dw to γ‐AlOOH could be realized by increasing the reaction temperature and 2) the morphological evolution of NH₄‐Dw and γ‐AlOOH nanostructures could be influenced by the concentration of the ionic liquid. Based on these experimental results, the main objective of this work was to clarify the effect models of the ionic liquids on the synthesis of NH₄‐Dw and γ‐AlOOH nanostructures, which could be divided into cationic‐ or anionic‐dominant effect models, as determined by the different surface structures of the targets. Specifically, under the cationic‐dominant regime, the ionic liquids mainly showed dispersion effects for the NH₄‐Dw nanostructures, whereas the anionic‐dominant model could induce the self‐assembly of the γ‐AlOOH particles to form hierarchical structures. Under the guidance of the proposed models, the effect of the ionic liquids would be optimized by an appropriate choice of cations or anions, as well as by considering the different effect models with the substrate surface. We expect that such effect models between ionic liquids and the target products will be helpful for understanding and designing rational ionic liquids that contain specific functional groups, thus open up new opportunities for the synthesis of inorganic nanomaterials with new morphologies and improved properties. In addition, these as‐prepared NH₄‐Dw and γ‐AlOOH nanostructures were converted into porous γ‐Al₂O₃ nanostructures by thermal decomposition, whilst preserving the same morphology. By using HRTEM and nitrogen‐adsorption analysis, the obtained γ‐Al₂O₃ samples were found to have excellent porous properties and, hence, may have applications in catalysis and adsorption.     

First Stereoselective Total Synthesis of a Dimeric Naphthoquinonopyrano‐γ‐lactone: (+)‐γ‐Actinorhodin

We have accomplished the first total synthesis of an isomerically pure naphthoquinonopyrano‐γ‐lactone dimer, γ‐actinorhodin, in eleven steps. Two steps exploit pairs of peri‐MeO groups as unusual selectivity controls. The respective MeO groups convey the steric bulk of a bromo or iodo substituent located ortho to one MeO group as steric hindrance into the vicinity of the second MeO group. This relay effect was indispensable for exerting regiocontrol in an aromatic bromination and diastereocontrol in an oxa‐Pictet–Spengler cyclization. The absolute configuration of our target compound was established in an asymmetric Sharpless dihydroxylation of a β,γ‐unsaturated ester, which was synthesized in a Heck coupling of a bromoiodonaphthalene with ethyl vinylacetate. The dihydroxylation provided the γ‐hydroxylactone moiety of the bromonaphthalene that was used as the substrate in the oxa‐Pictet–Spengler cyclization. Dimerization to the core of γ‐actinorhodin occurred by two Suzuki couplings.     

Single‐Flask Multicomponent Palladium‐Catalyzed α,γ‐Coupling of Ketone Enolates: Facile Preparation of Complex Carbon Scaffolds

A three‐component palladium‐catalyzed reaction sequence has been developed in which γ‐substituted α,β‐unsaturated products are obtained in a single flask by an α‐alkenylation with either a subsequent γ‐alkenylation or γ‐arylation of a ketone enolate. Coupling of a variety of electronically and structurally different components was achieved in the presence of a Pd/Q‐Phos catalyst (2 mol %), usually at 22 °C with yields of up to 85 %. Most importantly, access to these products is obtained in one simple operation in place of employing multiple reactions.     

Physicochemical characterization of α‐chitin, β‐chitin,and γ‐chitin separated from natural resources

We isolated α‐chitin, β‐chitin, and γ‐chitin from natural resources by a chemical method to investigate the crystalline structure of chitin. Its characteristics were identified with Fourier transform infrared (FTIR) and solid‐state cross‐polarization/magic‐angle‐spinning (CP–MAS) ¹³C NMR spectrophotometers. The average molecular weights of α‐chitin, β‐chitin, and γ‐chitin, calculated with the relative viscosity, were about 701, 612, and 524 kDa, respectively. In the FTIR spectra, α‐chitin, β‐chitin, and γ‐chitin showed a doublet, a singlet, and a semidoublet at the amide I band, respectively. The solid‐state CP–MAS ¹³C NMR spectra revealed that α‐chitin was sharply resolved around 73 and 75 ppm and that β‐chitin had a singlet around 74 ppm. For γ‐chitin, two signals appeared around 73 and 75 ppm. From the X‐ray diffraction results, α‐chitin was observed to have four crystalline reflections at 9.6, 19.6, 21.1, and 23.7 by the crystalline structure. Also, β‐chitin was observed to have two crystalline reflections at 9.1 and 20.3 by the crystalline structure. γ‐Chitin, having an antiparallel and parallel structure, was similar in its X‐ray diffraction patterns to α‐chitin. The exothermic peaks of α‐chitin, β‐chitin, and γ‐chitin appeared at 330, 230, and 310, respectively. The thermal decomposition activation energies of α‐chitin, β‐chitin, and γ‐chitin, calculated by thermogravimetric analysis, were 60.56, 58.16, and 59.26 kJ mol^?1, respectively. With the Arrhenius law, ln β was plotted against the reciprocal of the maximum decomposition temperature as a straight line; there was a large slope for large activation energies and a small slope for small activation energies. α‐Chitin with high activation energies was very temperature‐sensitive; β‐Chitin with low activation energies was relatively temperature‐insensitive. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3423–3432, 2004     

A simple synthesis of 5‐ethoxycarbonyl‐6‐phenyl‐1,3‐dioxin‐4‐ones and ethyl 3‐benzoyl‐4‐oxo‐2,6‐diphenylpyran‐5‐carboxylate

4‐Ethoxycarbonyl‐5‐phenyl‐2,3‐dihydrofuran‐2,3‐dione 1 reacts with aldehydes via the acylketene intermediate 2 giving the 1,3‐dioxin‐4‐ones 3a‐e and the 1,4‐bis(5‐ethoxycarbonyl‐4‐oxo‐6‐phenyl‐4H‐1,3‐dioxin‐2‐yl)benzene 4 , and a one step reaction between dibenzoylmethane and oxalylchloride gave 3,5‐dibenzoyl‐2,6‐diphenyl‐4‐pyrone 7 . The reaction of 1 with dibenzoylmethane, a dicarbonyl compound, provided ethyl 3‐benzoyl‐4‐oxo‐2,6‐diphenylpyran‐5‐carboxylate derivative 9 . Compound 9 was converted into the corresponding ethyl 3‐benzoyl‐4‐hydroxy‐2,6‐diphenylpyridine‐5‐carboxylate derivative 10 via its reaction with ammonium hydroxyde solution in 1 ‐butanol.     

γ‐Butyrolactone Copolymerization with the Well‐Documented Polymer Drug Carrier Poly(ethylene oxide)‐block‐poly(ε‐caprolactone) to Fine‐Tune Its Biorelevant Properties

Polymeric drug carriers exhibit excellent properties that advance drug delivery systems. In particular, carriers based on poly(ethylene oxide)‐block‐poly(ε‐caprolactone) are very useful in pharmacokinetics. In addition to their proven biocompatibility, there are several requirements for the efficacy of the polymeric drug carriers after internalization, e.g., nanoparticle behavior, cellular uptake, the rate of degradation, and cellular localization. The introduction of γ‐butyrolactone units into the hydrophobic block enables the tuning of the abovementioned properties over a wide range. In this study, a relatively high content of γ‐butyrolactone units with a reasonable yield of ≈60% is achieved by anionic ring‐opening copolymerization using 1,5,7‐triazabicyclo[4.4.0]dec‐5‐ene as a very efficient catalyst in the nonpolar environment of toluene with an incorporated γ‐butyrolactone content of ≈30%. The content of γ‐butyrolactone units can be easily modulated according to the feed ratio of the monomers. This method enables control over the rate of degradation so that when the content of γ‐butyrolactone increases, the rate of degradation increases. These findings broaden the application possibilities of polyester‐polyether‐based nanoparticles for biomedical applications, such as drug delivery systems.     

Ligand‐Controlled Direct γ‐C−H Arylation of Aldehydes

The first example of Pd^II‐catalyzed γ‐C(sp³)?H functionalization of aliphatic and benzoheteroaryl aldehydes has been developed using a transient ligand and an external ligand, concurrently. A wide array of γ‐arylated aldehydes were readily accessed without preinstalling internal directing groups. The catalytic mechanism was studied by performing deuterium‐labelling experiments, which indicated that the γ‐C(sp³)?H bond cleavage is the rate‐limiting step during the reaction process. This reaction could be performed on a gram scale, and also demonstrated its potential application in the synthesis of new mechanofluorochromic materials with blue‐shifted mechanochromic properties.     

Two Rare α‐Pyrone (=2H‐Pyran‐2‐one) Derivatives from Gentiana rhodantha Franchet

Two new rare α‐pyrone (=2H‐pyran‐2‐one) derivatives, rhodanthpyrones A and B ( 1 and 2 , resp.), together with fourteen known compounds, 3 – 16 , were isolated from the whole plants of Gentiana rhodantha. The structures of these compounds were elucidated by spectroscopic analyses. This is the first report on the occurrence of α‐pyrone derivatives in the genus Gentiana.     

Visible‐Light‐Driven N‐Heterocyclic Carbene Catalyzed γ‐ and ϵ‐Alkylation with Alkyl Radicals

The merging of photoredox catalysis and N‐heterocyclic carbene (NHC) catalysis for γ‐ and ?‐alkylation of enals with alkyl radicals was developed. The alkylation reaction of γ‐oxidized enals with alkyl halides worked well for the synthesis γ‐multisubstituted‐α,β‐unsaturated esters, including those with challenging vicinal all‐carbon quaternary centers. The synthesis of ?‐multisubstituted‐α,β‐γ,δ‐diunsaturated esters by an unprecedented NHC‐catalyzed ?‐functionalization was also established.     

An Activatable Photosensitizer Targeted to γ‐Glutamyltranspeptidase

We adopted a spirocyclization‐based strategy to design γ‐glutamyl hydroxymethyl selenorhodamine green (gGlu‐HMSeR) as a photo‐inactive compound that would be specifically cleaved by the tumor‐associated enzyme γ‐glutamyltranspeptidase (GGT) to generate the potent photosensitizer HMSeR. gGlu‐HMSeR has a spirocyclic structure and is colorless and does not show marked phototoxicity toward low‐GGT‐expressing cells or normal tissues upon irradiation with visible light. In contrast, HMSeR predominantly takes an open structure, is colored, and generates reactive oxygen species upon irradiation. The γ‐glutamyl group thus serves as a tumor‐targeting moiety for photodynamic therapy (PDT), switching on tumor‐cell‐specific phototoxicity. To validate this system, we employed chick chorioallantoic membrane (CAM), a widely used model for preliminary evaluation of drug toxicity. Photoirradiation after gGlu‐HMSeR treatment resulted in selective ablation of implanted tumor spheroids without damage to healthy tissue.     

Remarkable Stabilization of the α‐Helix Structure by an Intramolecular Host‐Guest Bridge in a Cyclodextrin‐Peptide Hybrid

A cyclodextrin‐peptide hybrid (CD‐peptide) bearing three units of γ‐cyclodextrin, cholic acid, and a dansyl fluorophore in the side chain has been prepared. In this novel CD‐peptide, the cholic acid unit acts as an internal guest and forms an intramolecular inclusion complex with γ‐cyclodextrin in the CD‐peptide. This intramolecular complex works as a host‐guest bridge in the CD‐peptide and remarkably stabilizes the α‐helix structure of the CD‐peptide.     

Chiral γ‐Lactams by Enantioselective Palladium(0)‐Catalyzed Cyclopropane Functionalizations

Cyclopropanes fused to pyrrolidines are important structural features found in a number of marketed drugs and development candidates. Typically, their synthesis involves the cyclopropanation of a dihydropyrrole precursor. Reported herein is a complementary approach which employs a palladium(0)‐catalyzed C? H functionalization of an achiral cyclopropane to close the pyrrolidine ring in an enantioselective manner. In contrast to aryl–aryl couplings, palladium(0)‐catalyzed C? H functionalizations involving the formation of C(sp³)? C(sp³) bonds of saturated heterocycles are very scarce. The presented strategy yields cyclopropane‐fused γ‐lactams from chloroacetamide substrates. A bulky Taddol phosphonite ligand in combination with adamantane‐1‐carboxylic acid as a cocatalyst provides the γ‐lactams in excellent yields and enantioselectivities.     

Two‐step Synthesis of New γ‐Lactones via Cyclization of 7‐Chloro‐2‐(methoxycarbonyl)‐4‐6‐dimethylocta‐(2E,4E,6E)‐trienoic acid

A new rapid synthesis of γ‐lactones, cis fused with a cyclopentenic ring by thermal cyclization of 7‐chloro‐2‐(methoxycarbonyl)‐4‐6‐dimethylocta‐7‐phenyl (or methyl) (2E,4E,6E)‐trienoic acids was reported. The key step implicates an intramolecular cyclization to a cyclopentenyl cation, according to an electrocyclic π_2s + π_2a conrotatory process, published in a recent paper (from the corresponding diacids). We have investigated the thermal behavior of the corresponding half‐esters since; if the cyclization obeys to the proposed mechanism, the diacids, half‐esters must also cyclize in a similar manner. Saponification of these led to γ‐dilactones via intermediary cyclopropanes. Mechanistic pathways were investigated.