Lactone Function Research Articles

Chalcone-Derived Lactones: Synthesis, Whole-Cell Biotransformation, and Evaluation of Their Antibacterial and Antifungal Activity.

Four compounds with lactone moiety were synthesized from chalcone 1 in three- or four-step synthesis. γ-Bromo-δ-lactone 5 was the only product of bromolactonization of acid 4 whereas bromolactonization of ester 3, apart from lactone 5 also afforded its isomer 6 and two diastereoisomeric δ-hydroxy-γ-lactones 7 and 8. Lactone 8 was also obtained in 88% yield as a product of simultaneous dehalogenation and translactonization of γ-bromo-δ-lactone 5 by Penicillum frequentans AM 359. Chalcone-derived lactones 5-8 were subjected to the tests on antimicrobial activity and the results compared with activity of starting chalcone 1. Obtained lactones 5-8 in most cases limited the growth of tested bacterial and fungal strains. The highest activity was found for δ-hydroxy-γ-lactone 8 which completely inhibited the growth of Staphylococcus aureus, Fusarium graminearum, Aspergillus niger, and Alternaria sp. The introduction of lactone moiety into chalcone scaffold significantly improved antimicrobial activity of the compound: γ-bromo-δ-lactone 6 and δ-hydroxy-γ-lactone 8 were significantly stronger growth inhibitors of S. aureus and F. graminearum. In the case of the latter, a clear positive effect of the lactone function on the antifungal activity was also observed for γ-bromo-δ-lactone 5.

Total Synthesis of Strasseriolide A.

Stereoselective total synthesis of structurally intriguing antimalarial macrolide strasseriolide A has been accomplished by adopting a convergent approach. The salient features of this synthesis include Co(BH4)2-mediated selective reduction of conjugated olefin, Crimmins propionate aldol, Evans alkylation, intermolecular Horner-Wadsworth-Emmons olefination, Yamaguchi macrolactonization, and selective saponification of ester moiety in the presence of a lactone functionality. The 13C{1H} NMR data of strasseriolide A were found to be very sensitive to its solution concentration.

Cobalt‐Catalyzed Deoxygenative Hydroboration of Nitro Compounds and Applications to One‐Pot Synthesis of Aldimines and Amides

AbstractThe commercially available and bench‐stable Co(acac)2 ligated with bis[(2‐diphenylphosphino)phenyl] ether (dpephos) was employed for selective room temperature hydroboration of nitro compounds with HBPin (TOF up to 4615 h−1), tolerating halide, hydroxy, amino, ether, ester, lactone, amide and heteroaromatic functionalities. These reactions offered a direct access to a variety of N‐borylamines RN(H)BPin, which were in situ treated with aldehydes and carboxylic acids to produce a series of aldimines and secondary carboxamides without the need for dehydrating and/or coupling reagents. Combination of these transformations in a sequential one‐pot manner allowed for direct and selective synthesis of aldimines and secondary carboxamides from readily available and inexpensive nitro compounds.magnified image

IR spectral fingerprints of carbonyl groups in graphite oxide: a theoretical study

Non-empirical quantum chemical calculations of various possible fragments in the oxidized carbon layer of graphite oxide were carried out at the DFT level with the hybrid B3LYP functional and the extended double-zeta Gaussian basis set. These fragments contain the carbonyl groups as ketone, carboxyl and lactone functions, either free or hydrogenbonded to hydrating water molecules or closely arranged hydroxyl groups. Using the vibrational energy distribution analysis, the typical spectral ranges of C=O vibrations were identified within the fingerprint region of 1550–1800 cm−1 depending on the kind of the carbonyl group studied and its environment.

REVIEW OF COMPUTATIONAL STUDIES APPLIED IN NEW MACROLIDE ANTIBIOTICS

Macrolide antibiotics have been the focus of widespread research due to increasing bacterial resistance. There have been significant synthetic and theoretical efforts to generate new core structures to address this challenge. Structure elucidation of a large number of macrolides, shows the existence of two parts. The first one is a macrocyclic system from 12 to 40 links with several asymmetric centers and a lactone function; the second part is a sugar. Macrolide antibiotics play a therapeutically important role, particularly in the emergence of new pathogens. Among these products of major importance are macrolide antibiotics. The macrolide antibiotics family (14-, 15-, 16- membered ring derivates) shows a wide range of antibacterial spectrum. Conformational analysis indicates that each studied macrocycle presents eight families of privileged conformers. They result from the combination of the conformations of the two systems, diene anda,b-unsaturated ester. In presence of tricarbonyliron, the number of the privileged conformations was reduced to four. The study of stereochemical control in macrocycles was carried out using molecular mechanics and molecular dynamics. The results show a high conformational mobility of macrocycles. For complexing macrocycles, a high diastereoselectivity was obtained, this is the result from the combination of local control exerted by the methyl group and stereochemical control with tricarbonyliron. This last factor constitutes a tool of the stereochemical remote control, which permits to foresee the phenomenon of the stereoselectivity for envisaged reactions.

Heterogeneous Olefin Hydrogenation Enabled by a Highly-Reduced Nickel(-II) Catalyst Precursor.

The hydrogenation of olefins, styrenes, enoates, imines, and sterically hindered tri‐substituted olefins was accomplished using the pre‐catalyst dilithiumbis(cycloocta‐1,5‐diene)nickelate(−II) (1). The mild conditions tolerate hydroxyl, halide, ester, and lactone functionalities. Mechanistic studies, including reaction progress analyses, poisoning experiments, and multinuclear NMR monitoring, indicate that a heterotopic (nickel nanoparticle) catalyst is in operation.

Efficient Co-Catalyzed Double Hydroboration of Nitriles: Application to One-Pot Conversion of Nitriles to Aldimines.

The commercially available and bench-stable Co(acac)2 /dpephos system is employed as a precatalyst for selective and efficient room temperature hydroboration of organic nitriles with HBPin to produce a series of N,N-diborylamines [RN(BPin)2 ], which react in situ with aldehydes to give aldimines. Formation of aldimines from N,N-diborylamines does not require a dehydrating agent, is applicable to a wide range of N,N-diborylamine and aldehyde substrates and is highly chemoselective, being unaffected by various common functional groups, such as alkenes, alkynes, secondary amines, ketones, esters, amides, carboxylic acids, pyridines, nitriles, and nitro compounds. The overall transformation represents a synthetically valuable approach to aldimines from nitriles and can be performed in a sequential one-pot manner, tolerating ester, lactone, carboxamide and unactivated alkene functionalities.

Organoborane Strategy for Polymers Bearing Lactone, Ester, and Alcohol Functionality

Vinyl alcohol–methacrylatecopolymers have intriguing functionally rich structures but are synthetically inaccessible from vinyl acetate, the traditional precursor to polyvinyl alcohol. We report a ...

Synthesis and Antimicrobial Activity of Methoxy- Substituted γ-Oxa-ε-lactones Derived from Flavanones.

Six γ-oxa-ε-lactones, 4-phenyl-3,4-dihydro-2H-1,5-benzodioxepin-2-one (5a) and its five derivatives with methoxy groups in different positions of A and B rings (5b–f), were synthesized from corresponding flavanones. Three of the obtained lactones (5b,c,f) have not been previously described in the literature. Structures of all synthesized compounds were confirmed by complete spectroscopic analysis with the assignments of signals on 1H and 13C-NMR spectra to the corresponding atoms. In most cases, lactones 5a–f exerted an inhibitory effect on the growth of selected pathogenic bacteria (Escherichia coli, Bacillus subtilis, and Staphylococcus aureus), filamentous fungi (Fusarium graminearum, Aspergillus niger, and Alternaria sp.), and yeast (Candida albicans). The broadest spectrum of activity was observed for unsubstituted lactone 5a, which was particularly active against filamentous fungi and yeast. Lactones with methoxy groups in the 3′ (5c) and 4′ (5d) position of B ring were more active towards bacteria whereas lactone substituted in the 7 position of the A ring (5e) exhibited higher antifungal activity. In most cases, the introduction of lactone function increased the activity of the compound compared to its flavonoid precursors, chalcones 3a–e, and flavanones 4a–f.

Iridium-Catalyzed Reductive Allylation of Esters.

The catalytic reductive transformation of carboxylic esters into α-branched ethers is described. The procedure pivots on the chemoselective iridium-catalyzed hydrosilylation of ester and lactone functionality to afford a silyl acetal intermediate. Upon treatment with a Lewis acid, these hemilabile intermediates dissociate to form reactive oxocarbenium ions, which can be intercepted by allyltributyltin nucleophiles, resulting in the formation of valuable α-branched alkyl-alkyl ether derivatives. This reductive allylation procedure was found to be amenable to a range of carboxylic ester starting materials, and good chemoselectivity for ethyl over tert-butyl esters was demonstrated. Furthermore, downstream synthetic manipulation of α-amino acid-derived products led to the efficient formation of pyrrolidine, piperidine, and azepane frameworks.

Celite‐Polyaniline supported palladium catalyst for chemoselective hydrogenation reactions

Polyaniline coated on particles of celite is used as support to load palladium catalyst. This heterogenized Celite•PANI•Pd system, is used as an efficient catalyst for chemoselective hydrogenation reactions. The catalyst is characterized by usual spectral, analytical techniques and studied for hydrogenation reactions at ambient conditions. The mild reaction conditions allow the control over the reactions and excellent selectivity is achieved in number of conversions. Hydrogenation of a carbon–carbon double bond was favored over other polar π‐bond systems, while labile functional groups such as benzyl ether, benzyl esters, cyano, nitro and halogen remained unaffected. Primary amines were converted to N,N‐dimethyl amines with formaldehyde, the double bond of coumarin was selectively hydrogenated without opening of the lactone functionality.

Controlled derivatization of hydroxyl groups of graphene oxide in mild conditions

Graphene oxide (GO) is constituted of various oxygen-containing functionalities, primarily epoxides and hydroxyl groups on the basal plane, with a very low amount of carbonyl, quinone, carboxylic acid, phenol, and lactone functions at the edges. The high chemical reactivity of these oxygenated groups makes functionalization difficult to control as different reactions can occur concomitantly. In this study we have investigated the reactivity of GO towards orthogonal reactions to selectively functionalize the hydroxyl groups, which are present in a high amount. We explored both the esterification and the Williamson reaction. Our strategies present the main advantage to occur in mild conditions, thus preserving the intrinsic properties of GO, whereas most reactions reported in literature require relatively harsh conditions, leading to (partial) reduction, and/or are not chemoselective. We have also extended our study to the ketones and examined their derivatization by the Wittig reaction. This work has allowed developing two facile methods for the covalent derivatization of the hydroxyl groups in mild conditions, while GO was not reactive towards the Wittig reaction, probably due to the low amount of ketones. Overall, this work leads to a better understanding of the reactivity of GO for controlled derivatization. This opens promising perspectives for multi-functionalization of GO in order to design graphene-based nanomaterials endowed of multiple properties.

In Situ Spectroscopic and Computational Studies on a MnO2-CuO Catalyst for Use in Volatile Organic Compound Decomposition.

In situ near-edge X-ray absorption fine structure (NEXAFS) spectroscopy and density functional theory calculations were conducted to demonstrate the decomposition mechanism of propylene glycol methyl ether acetate (PGMEA) on a MnO2–CuO catalyst. The catalytic activity of MnO2–CuO was higher than that of MnO2 at low temperatures, although the pore properties of MnO2 were similar to those of MnO2–CuO. In addition, whereas the chemical state of MnO2 remained constant following PGMEA dosing at 150 °C, MnO2–CuO was reduced under identical conditions, as confirmed by in situ NEXAFS spectroscopy. These results indicate that the presence of Cu in the MnO2–CuO catalyst enables the release of oxygen at lower temperatures. More specifically, the released oxygen originated from the Mn–O–Cu moiety on the top layer of the MnO2–CuO structure, as confirmed by calculation of the oxygen release energies in various oxygen positions of MnO2–CuO. Furthermore, the spectral changes in the in situ NEXAFS spectrum of MnO2–CuO following the catalytic reaction at 150 °C corresponded well with those of the simulated NEXAFS spectrum following oxygen release from Mn–O–Cu. Finally, after the completion of the catalytic reaction, the quantities of lactone and ether functionalities in PGMEA decreased, whereas the formation of C=C bonds was observed.

Cytotoxic Spiroepoxide Lactone and Its Putative Biosynthetic Precursor from Goniobranchus Splendidus.

Epoxygoniolide-1 (1), possessing spiroepoxide lactone, enal, and masked dialdehyde functionalities, has been characterized from the conspicuously patterned mollusc Goniobranchus splendidus. Its relative configuration was investigated by spectroscopic analyses, molecular modeling, and density functional theory calculations. The biosynthesis of 1 may involve rearrangement of a diterpene framework, providing a precursor to cometabolite gonioline (2), followed by C–C bond cleavage (via Grob or P450 mechanism). Moderate cytotoxicity to NCIH-460, SW60, or HepG2 cancer cells was observed for norditerpene 1.

Development of Green/Red-Absorbing Chromophores Based on a Coumarin Scaffold That Are Useful as Caging Groups.

We report the design, synthesis, and spectroscopic characterization of a series of push-pull chromophores based on a novel coumarin scaffold in which the carbonyl of the lactone function of the original coumarin dyes has been replaced by the cyano(4-nitrophenyl)methylene moiety. The skeleton of the compounds was synthesized by condensation of a thiocoumarin precursor with the corresponding arylacetonitrile derivatives, and their photophysical properties were fine-tuned through the incorporation of electron-withdrawing groups (EWGs) like nitro and cyano at the phenyl ring, leading to absorption in the green to red region. Although fluorescence emission was weakened or even canceled upon introduction of two or three strong EWGs, the emission of the mononitro-containing coumarin derivatives in the red region upon excitation with green light is noticeable, as are their significantly large Stokes shifts. The new coumarin derivatives can be useful as photocleavable protecting groups, as demonstrated through the synthesis and characterization of a series of coumarin-based photocages of benzoic acid. Preliminary photolysis studies with green light have demonstrated that the structure of the coumarin chromophore influences the rate of the uncaging process, opening the way to exploiting these new coumarin scaffolds as caging groups that can be removed with visible light.

Photooxidation of cellulose nitrate: New insights into degradation mechanisms

Cellulose nitrate (or nitrocellulose) has received considerable interest due to its uses in various applications, such as paints, photographic films and propellants. However, it is considered as one of the primary pollutants in the energetic material industries because it can be degraded to form polluting chemical species. In this work, the UV light degradation of cellulose nitrate films was studied under conditions of artificially accelerated photooxidation. To eliminate the reactivity of nitro groups, the degradation of ethylcellulose was also investigated. Infrared spectroscopy analyses of the chemical modifications caused by the photooxidation of cellulose nitrate films and the resulting formation of volatile products revealed the occurrence of de-nitration and the formation of oxidation photoproducts exhibiting lactone and anhydride functions. The impact of these chemical modifications on the mechanical and thermal properties of cellulose nitrate films includes embrittlement and lower temperatures of ignition when used as a propellant.

Baeyer-Villiger Oxidation of Some C19 Steroids by Penicillium lanosocoeruleum

The biotransformation of androsterone (1), epiandrosterone (2), androstanedione (3) and DHEA (dehydroepiandrosterone) (4) by Penicillium lanosocoeruleum—a fungal species not used in biotransformations so far—were described. All the substrates were converted in high yield (70%–99%) into d ring δ-lactones. The oxidation of 1 produced 3α-hydroxy-17a-oxa-d-homo-5α-androstan-17-one (5). The oxidation of 2 led to 3β-hydroxy-17a-oxa-d-homo-5α-androstan-17-one (6). The biotransformation of 3 resulted in the formation of 3α-hydroxy-17a-oxa-d-homo-5α-androstan-17-one (5) and 17a-oxa-d-homo-5α-androstan-3,17-dione (7). An analysis of the transformation progress of the studied substrates as a function of time indicates that the Baeyer-Villiger monooxygenase of this fungus does not accept the 3β-hydroxy-5-ene functionality of steroids. In this microorganism steroidal 3β-hydroxy-dehydrogenase (3β-HSD) was active, and as a result DHEA (4) was transformed exclusively to testololactone (8). Apart from the observed oxidative transformations, a reductive pathway was revealed with the C-3 ketone being reduced to a C-3α-alcohol. It is demonstrated for the first time that the reduction of the 3-keto group of the steroid nucleus can occur in the presence of a ring-D lactone functionality.

ChemInform Abstract: Unusual Skeletal Rearrangement of Unsaturated Seven‐Membered Lactams into Fused Pyrrolidinolactones.

AbstractSeveral subsequent modifications of the lactone functionality of the reaction products are exemplified.

Structure-related antifeedant activity of halolactones with a p -menthane system against the lesser mealworm, Alphitobius diaperinus Panzer

Feeding deterrent activity of synthetic halogen lactones against larvae and adults of the lesser mealworm, Alphitobius diaperinus Panzer, in laboratory choice and no-choice tests was studied. The compounds were synthesised from racemic and enantiomerically enriched (ee = 91-98%) cis- and trans-piperitols, which were obtained from (±)-piperitone. Structure-activity relationship studies identified several synthetic halolactones with a very strong feeding deterrent activity. The most active were the enantiomeric chlorolactones with chiral centre configurations (1S,4S,5R,6R) and (1R,4R,5S,6S) and their racemic mixture. The racemic bromo- and iodolactones obtained from cis-piperitol and saturated lactones with a chiral centre configuration (1R,4S,6R) were also very good antifeedants in comparison with piperitone. Most of the studied compounds were better antifeedants against adults than against larvae-among the 21 compounds, only one bromolactone with a chiral centre configuration (1S,4R,5R,6R) was a weaker deterrent for adults. Chemical transformation of the piperitone molecule by the introduction of a lactone function and a halogen atom strongly changed its antifeedant properties against the lesser mealworm. Optimum activity is dependent on the presence of a chlorine atom at C-5 of the cyclohexane ring. The activity of bromo- and iodolactones depended strongly on the chiral centre configuration and the halogen substituent.

New bio-derived superabsorbents from nature

Superabsorbent polymers have been around for nearly half a century. Presently, petroleum-based polyacrylic acid-type polymers are used in the majority of superabsorbent applications and markets. However, the rising costs of petroleum and the lack of a sustainable supply of fossil-based chemicals is driving a need for alternative, renewable based chemicals. Herein, we report the synthesis and superabsorbent properties of novel polymers derived from nature. Free-radical, emulsion polymerization methods were used to generate cross-linked polyacrylates containing lactone functionality, which were saponified into the corresponding cross-linked ionomers in a second step. The final cross-linked products displayed >50× absorption of water per weight of polymer and absorption under load of >15× the weight of saline solution per weight of polymer. The technology also offers the opportunity to perform additional chemistry and modification to the polymer backbone in order to improve its properties.