Trans-fused Lactones Research Articles

An Approach to the 9-Oxo-10-oxabicyclo[5.3.0]dec-2-ene Core of the Guaianolide and Pseudoguaianolide Sesquiterpenes via a Domino Electrocyclic Ring-Opening/Carboxylic Acid Trapping of a gem-Dibromocyclopropane.

A domino silver(I)-promoted electrocyclic 2π-disrotatory electrocyclic ring-opening/intramolecular nucleophilic trapping of [ n.1.0]-dibromocyclopropanes by tethered carboxylic acids results in cyclization to butyrolactones fused to six- and seven-membered carbocycles. In the case of bicyclic [4.3.0] lactones the cis-fused stereoisomer was formed, whereas for the bicyclic [5.3.0] lactones the trans-fused stereoisomer was formed. Optimal conditions for the reaction used silver(I) trifluoroacetate (2.0 equiv) in trifluoroethanol or with added pyridine (2.0 equiv) and NaPF6 (5.0 equiv). The dibromocyclopropane precursors were made through cyclopropanation with in situ-generated dibromocarbene. The trans-fused lactones are potentially useful building blocks for pseudoguaianolide, guaianolide, and xanthanolide total synthesis. A computational study on the conformational preferences of these systems indicates that the trans-fused bicyclic [5.3.0] butyrolactones are lower in energy than the corresponding cis-fused lactones at the B3LYP/cc-pVTZ level of theory.

Isolation and Identification of Nepetalactone Diastereomers from Commercial Samples of Nepeta cataria L. (Catnip): An Introductory Organic Laboratory Experiment

The essential oil of Nepeta cataria L. (catnip), an herbaceous plant known popularly as a stimulant for the domestic cat, is enriched in two diastereomeric iridoid lactones (nepetalactones) that vary in ratio. Although the diastereomers are chromatographically separable and exhibit different 1D NMR spectra, it is not possible to differentiate between them chromatographically or spectroscopically without previous knowledge or more complex NMR experiments; however, the trans-fused lactone readily epimerizes to the thermodynamically more stable cis-fused lactone upon treatment with base. Students in the introductory organic laboratory establish the presence of the two major nepetalactones in catnip essential oil by TLC and GC–MS analysis, assigning TLC spots and GC peaks to specific lactones by chromatographic comparison of the essential oil with the product of epimerization (i.e., cis-fused lactone) and determining the diastereomeric ratio of nepetalactones by GC peak integration.

On the Diels–Alder reactions of pentadienyl maleates and citraconates

Reactions between conjugated dienols and maleic anhydride provide either cis-fused or trans-fused bicyclic products as major products, depending upon how the reaction is carried out. Simply mixing the two reactants together generally leads to cis-fused lactone acids in thermal reactions which proceed viaintermolecular Diels-Alder reaction followed by intramolecular esterification. Pre-forming the maleate half ester derivative followed by heating affords predominantly trans-fused lactone acids in good yields by way of an intramolecular Diels-Alder (IMDA) reaction. Sorbyl citraconate half esters undergo a rapid thermolytic fragmentation in refluxing toluene to form the dienol and citraconic anhydride. The resulting diene-dienophile pair undergo an intermolecular cycloaddition followed by a rapid intramolecular esterification to give cis-fused bicyclic lactone acids as major products. The IMDA reaction of citraconic half esters is sufficiently rapid in DMSO to dominate over fragmentation: the exo-cycloadduct is formed almost exclusively. Nine literature reports of endo-selective IMDA reactions of triene acids are erroneous; the cycloadditions proceed in an intermolecular manner.

Synthesis and binding affinity studies of muscarinic receptor antagonists related to dehydrohimbacine

The intramolecular Diels-Alder reaction of bromo-substituted nonatrienoate 24 leads to a mixture of the anti-adducts 25a and 25b, in which the trans-fused lactone 25b, the result of an expected exo-addition, predominates (6.2: 1 stereoselectivity). Further introduction of a 2,6-trans-disubstituted piperidine ring ( 26 and 27) via palladium catalyzed cross-coupling reactions (Stille and Sonogashira) affords intermediates that are easily transformed into dehydrohimbacine derivatives 14a, 14b, 15a, and 15b. Binding affinity studies for the muscarine receptors M-1, M-2, M-3, and M-4 show that 15a possesses a 18-fold selectivity for the M-2 relative to the M-1 receptor, but with concomittant loss in affinity compared to the naturally occurring (+)- himbacine ( 1), a recognized muscarinic receptor antagonist.

From glyceraldehyde to functionalized enantiopure tetrahydronaphthalenes and indanes

Tricyclic tetrahydronaphthalenes comprising cis- and trans-fused lactones, and aryl substituted functionalized indanes were synthesized in enantiopure form.

Synthetic [5,5] trans-fused indane lactones as inhibitors of thrombin

Synthesis of trans-fused lactones containing the indane nucleus has resulted in a series of potent acylating inhibitors of thrombin. As an example compound 11e has an apparent second order rate constant of 11×10 6 M −1 sec −1 for the inhibition of thrombin. The anticoagulant activity of these compounds is discussed.

ChemInform Abstract: A Stereoselective Synthesis of cis‐ and trans‐Fused Lactones via the Palladium(II)‐Catalyzed Carbonylation of Organomercurials.

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A stereoselective synthesis of cis- and trans-fused lactones via the palladium(II)-catalyzed carbonylation of organomercurials

Organomercurials 2a-c, obtained by the regioselective, Hg(II)-mediated cleavage of cyclopropyl alcohols 1a-c, are converted into the corresponding 5-membered cis-annulated lactones 3a-c via the Pd(II)-catalyzed carbonylation in the presence of p-benzoquinone. Isomeric, trans-fused lactones can be synthesized in a similar way ( 6→7). The carbonylation occurs under an atmospheric pressure of CO.

A New Synthesis of Podophyllum Lignans by Weitz' Aminium Salt-Induced Free Radical Cycloaddition Reaction of a Doubly Unsaturated Ester.

(±)-Isopodophyllotoxin (1e) and related lactones 12, 13, 14 were synthesized by a biomimetic procedure from the doubly unsaturated esters 11a and 11b by means of an oxidative free radical cycloaddition reaction utilizing a stable cation radical salt, Weitz' aminium salt, in one step. (±)-Isopicropodophyllin (1g), the trans-fused lactones, 12, 13, and 16, and the cis-fused lactone 17 were also synthesized from the esters 11c and 11b by the reaction with the same reagent.

Co-occurrence of eremophilanes and eudesmanes in Artemisia pectinata

The aerial parts of Artemisia pectinata afforded, in addition to a typical spiroketal enol ether and the known eremophil-9,11(13)-dien-12-oic acid, the corresponding 8,12-lactone as well as two eudesmane derivatives, a hydroxy and an acetoxy acid. The co-occurrence of eremophilanes and eudesmanes and the absence of the corresponding eudesman-8,12-olide with a trans-fused lactone ring is remarkable.

The chemistry of santonene. Part VIII. Photoreaction of 4αH-pyrosantonin

Irradiation of 4αH-pyrosantonin [(11S)-3-oxo-4αH-eudesma-1,5-dien-12,6-olactone](7) affords four isomeric photopyrosantonins A–D [(9)–(12)], each possessing a spiro(bicyclo[3.1.0]hexane)-6,1′-cyclopentaneskeleton. The two trans-fused lactones A and D [(9) and (12)] are readily hydrolysed to give the same diketo-acid (17a) with opening of the lactone and cyclopropane rings. The cis-fused lactones, B and C [(10) and (11)] are more stable but on treatment with acid afford the diketo-acid (18a). The cis-lactones can be equilibrated photochemically and by acid. The trans-lactones can be equilibrated photochemically. Pyrolysis of dihydro-derivatives of the trans-lactones affords the corresponding derivatives of the cis-lactones. The mechanism of the photochemical reaction is discussed; the pathway from the trans-lactone to the diketo-acid (17) has been followed by use of a deuterium-labelling technique.