Lactones 5a Research Articles

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.

Effects of α,β-unsaturated lactones on larval survival and gut trypsin as well as oviposition response of Aedes aegypti

Lactones are organic cyclic esters that have been described as larvicides against Aedes aegypti and as components of oviposition pheromone of Culex quinquefasciatus. This work describes the effect of six α,β-unsaturated lactones (5a–5f) on survival of A. aegypti fourth instar larvae (L4). It is also reported the effects of the lactones on L4 gut trypsin activity and oviposition behavior of A. aegypti females. Five lactones were able to kill L4 being the lactones 5a (LC50 of 39.05 ppm), 5e (LC50 of 36.30 ppm) and 5f (LC50 of 40.46 ppm) the most promising larvicides. Only the lactone 5a inhibited L4 gut trypsin activity, with an IC50 of 115.15 µg/mL. Lactones 5a, 5c, 5d and 5e did not exert deterrent or stimulatory effects on oviposition, whereas lactone 5b exhibited a strong deterrent oviposition activity. In conclusion, this work introduces new α,β-unsaturated lactones as promising alternatives to control A. aegypti dissemination. The larvicidal mechanism of the lactone 5a can involve the disruption of proteolysis at larval gut.

Selectivity controlled by ligand tuning in the palladium-catalysed cyclocarbonylation: Synthesis of new γ and δ lactones from a natural sesquiterpene

The cyclocarbonylation of homoallylic alcohols, derived from α-atlantone, catalysed by [Pd(Cl2)L2]/SnCl2] system, afforded new γ and δ lactones as the main products with high selectivities. The regiochemical control depends on the nature of phosphines involved. Catalysts based on monophosphines with large cone angles such as tricyclohexyl phosphine produce the six-membered ring lactones with selectivities up to 80%, while diphosphines with wide bite angle such as xantphos are found to favor the five-membered ring lactones with up to 99% selectivity. Monocrystals of the γ and δ lactones suitable for X-ray diffraction analysis have been obtained and the stereochemistry of the lactones 5a,a′ and 6 have been elucidated. This study is the first example of an attractive catalytic transformation of one single natural sesquiterpene easily available from bio-renewable resources to obtain either γ- or δ-lactones.

ChemInform Abstract: Synthesis of 4,7-Dihydroxyperhydroisobenzofuran-1-one and Comparison with Zwergal′s Structure of “Garlicin”.

The Diels-Alder reaction of 2-(benzoyloxy)furan (2) with maleic anhydride leads to the adduct 3 which, on hydrogenation, affords the exo anhydride 4a (71%) and endo anhydride 4b (2.4%). The regioselective reduction of 4a and 4b with NaBH4 leads to the lactones 5a and 5b, respectively. Base-catalyzed cleavage of 5a gives the keto lactone 6 or dimethyl acetal 7, depending on the reaction conditions. Catalytic hydrogenation of keto lactone 6 results in the diastereoselective formation of the title compound 8a which has been converted into the acetate 8b and trifluoroacetate 8c. The structure and properties of the dihydroxylactone 8a are discussed in comparison with garlic compound “garlicin”.

A simple synthesis of cytotoxic endoperoxide lactones

A series of dihydrobenzofuran-2-one 3 have been submitted to various dienophiles: whereas maleic anhydride led only to the adducts 4a, b, singlet oxygen gave the expected new endoperoxide lactones 5a– d, 6 and 7a, b, three of them showing interesting cytotoxicity towards various cancer cell lines.

Regioselective Spiroannulations of α-Acetyl Lactones.

For Abstract see ChemInform Abstract in Full Text.

Regioselective Spiroannulations of α‐Acetyl Lactones

AbstractMonocyclic spiroannulation precursors 3a−c were obtained by Michael reactions of α‐acetyl lactones 6a−c with methyl vinyl ketone (7). The selective formation of either regioisomer of both β‐oxo (5a−c) and δ‐oxo (4a−c) lactones from 3a−c was achieved by varying the reaction conditions. The δ‐oxo lactones 4a−c were obtained under basic (buffered) conditions in a pyrrolidine/AcOH system. Under acidic conditions, the annulation reaction afforded β‐oxo lactones 5a−c. Byproducts 8b,c were identified to be the decomposition products of β‐oxo lactones 5b and 5c by comparison with the spectra of the alcohols 10b,c derived directly from δ‐oxo lactones 4b and 4c by saponification/decarboxylation. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Highly Regio- and Stereoselective Cocyclotrimerization and Linear Cotrimerization of alpha,beta-Unsaturated Carbonyl Compounds with Alkynes Catalyzed by Nickel Complexes.

Cyclic enones 2-cyclohexen-1-one (1a), 4,4-dimethyl-2-cyclohexen-1-one (1b), 2-cyclopenten-1-one (1c), and 2-cyclohepten-1-one (1d) react with octa-1,7-diyne (2) in THF in the presence of Ni(PPh(3))(2)I(2), ZnI(2), and Zn powder at 62 degrees C to give [2 + 2 + 2] cycloaddition-dehydrogenation products 3a-d in 32-80% yields. alpha,beta-Unsaturated lactone 5a (5,6-dihydro-2H-pyran-2-one) undergoes [2 + 2 + 2] cycloaddition with 2 to give both the corresponding cyclohexadiene product 6 (29%) and dehydrogenation product 7 (39%). Under similar reaction conditions, 3-buten-2-one reacts with 2 and various substituted hepta-1,6-diynes 9a-c to give [2 + 2 + 2] cycloaddition-dehydrogenation products 11a-d in 68-80% yields. Diphenylacetylene also reacts with 1a-d, 5a, and 2(5H)-furanone (5b) to afford the corresponding [2 + 2 + 2] cocyclotrimerization products 13a-d and 14a-b. No dehydrogenation of products 13 and 14 was observed under the reaction and workup conditions. The reactions of acrylates with alkynes catalyzed by nickel complexes give products that depend greatly on the reaction conditions. Treating ethyl acrylate (15a) with 1-phenyl-1-propyne (16) in the presence of Ni(PPh(3))(2)Cl(2) and Zn at 90 degrees C in toluene affords cocyclotrimerization product 19aas the major product (54% yield). However, treatment of CH(2)CHCOOR (R = Et and t-Bu) with mono alkynes 16 and 12 in the presence of Ni(PPh(3))(2)X(2) (X = Cl and I) and Zn powder in toluene at 60 degrees C affords the corresponding conjugated trienes 17a-c in 82-92% yields. The MS data of 17firmly support an adduct of two molecules of alkyne and a molecule of acrylate. Similarly, the reaction of 15a with octa-1,7-diyne in the presence of Ni(PPh(3))(2)I(2), ZnI(2), and zinc gives triene derivative 21 in 68% yield. NOE and X-ray results indicate that in these trienes the substituents from each alkyne and alkene moiety are cis to each other. The unique stereoselectivity can be attributed to the exclusive formation of seven-membered nickelacycloheptadiene intermediate 25during the catalytic reaction.

A Short Synthesis of the New Vallesiachotamine Lactone from Cephaelis dichroa (Standley)

The new vallesiachotamine lactone (1) is synthesized from lactone 5aby selenium mediated dehydrogenation. Lactone 5a was previously prepared from deprotonated butyrolactone Li-4 and the pyridinium salt 3 (Wenkert reaction).

Enantioselective Syntheses of (-)- and (+)-Homocitric Acid Lactones.

Highly enantioselective syntheses of enantiomers of homocitric acid lactones (R)-5a and (S)-5b are described. Thermal Diels-Alder cycloadditions of 2a and 2b to 1,3-butadiene produced adducts 3a and 3b, respectively. Oxidative ozonolysis of latter adducts gave products 4a and 4b which after acid treatment afforded a mixture with 5a and 5b as major component. Acid lactones 5a and 5b were converted into their dimethyl esters 6a and 6b which were purified by chromatography. After saponification, the products obtained were crystallized to yield (-)- and (+)-homocitric acid lactones ((R)-5a and (S)-5b). Diastereomeric excess (de) of Diels-Alder adducts 3a and 3b was determined by means of Mosher esters of glycols 8a, 8b, and racemic 8. Diels-Alder cycloaddition products of lactones 2a and 2b to 1,3-butadiene showed a diastereoselectivity of 96%.

Synthesis of 4,7‐Dihydroxyperhydroisobenzofuran‐1‐one and Comparison with Zwergal's Structure of “garlicin”

AbstractThe Diels‐Alder reaction of 2‐(benzoyloxy)furan (2) with maleic anhydride leads to the adduct 3 which, on hydrogenation, affords the exo anhydride 4a (71%) and endo anhydride 4b (2.4%). The regioselective reduction of 4a and 4b with NaBH4 leads to the lactones 5a and 5b, respectively. Base‐catalyzed cleavage of 5a gives the keto lactone 6 or dimethyl acetal 7, depending on the reaction conditions. Catalytic hydrogenation of keto lactone 6 results in the diastereoselective formation of the title compound 8a which has been converted into the acetate 8b and trifluoroacetate 8c. The structure and properties of the dihydroxylactone 8a are discussed in comparison with garlic compound “garlicin”.

Pseudoesters and derivatives. XXVI. Formation of cyclopropanes and five membered heterocycles by michael initiated ring closure reactions of 2-bromo-3-formylacrylic acid derivatives

The reaction of 3-bromo-5-methoxyfuran-2(5 H)-one l with the stabilized carbanions derived from 2a–d, in a solid-liquid two-phase system in the presence of potassium carbonate and tetrabutylammonium bromide, affords the cyclopropane lactones 5a–d. With the ambident anions generated from 2e and 2f, the fused heterocyclic compounds 10 and 11, respectively, are obtained. The reaction of methyl 2-bromo-4,4-dimethoxy-2-butenoates ( 7, 8) with 2b–f, under similar conditions, gives rise to mixtures of the functionalized cyclopropanes 12b–f and 13b–f as mixtures of diastereoisomers; dihydrofurans 14 and 15 are also formed as minor components using ethyl acetoacetate ( 2f) as nucleophile.