Α-methylene Γ-lactones Research Articles

Rapid Access to 2-Methylene Tetrahydrofurans and γ-Lactones: A Tandem Four-Step Process.

A one-pot tandem process involving hydrolysis, Knoevenagel condensation, Michael addition, and Conia-ene (HKMC) reactions has been developed for the rapid synthesis of indanone-fused 2-methylene tetrahydrofurans from the reaction of enynals and propynols. In this process, two rings and four bonds are generated with 100 % atom-economy and high step-efficiency. The resulting tetrahydrofurans were readily oxidized into α-methylene γ-lactones, which are one of the most important substructures in natural and bioactive compounds.

Efficient transformation of 7,14-dihydroxy-ent-kaurenes to novel ent-abietanes having cis-fused α-methylene γ-lactones under Mitsunobu reaction conditions and their cytotoxicities

Transformation of plant-origin 7,14-dihydroxy-ent-kaurenes to ent-abietanes having a cis-fused α-methylene γ-lactones was accomplished efficiently under the Mitsunobu reaction conditions. The yields of the desired products were apparently influenced by the steric hindrance at C-1. The cytotoxic activity on P388 murine leukemia cells of the ent-abietanes having cis-fused α-methylene γ-lactones produced were assayed.

Eudesmane-type sesquiterpene lactones inhibit multiple steps in the NF-κB signaling pathway induced by inflammatory cytokines

Inflammatory cytokines, such as interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α), induce the intracellular signaling pathway leading to the activation of nuclear factor κB (NF-κB). A series of eudesmane-type sesquiterpene lactones possessing an α-methylene γ-lactone group and/or an α-bromo ketone group were synthesized and evaluated for their inhibitory effects on the NF-κB-dependent gene expression and signaling pathway. Our present study reveals that eudesmane-type α-methylene γ-lactones and α-bromo ketones inhibit multiple steps in the NF-κB signaling pathway induced by IL-1α and TNF-α.

Efficient synthesis of novel cytotoxic cis-fused α-methylene γ-lactones from 7,14-dihydroxy-ent-kaurenes by transformation under Mitsunobu reaction conditions

Facile transformation of 7,14-dihydroxy-ent-kaurenes such as excisanin A (8), kamebanin (9), and kamebakaurin (10), which are abundant in plants of the genus Rabdosia species (Labiatae), to ent-abietanes was accomplished under the Mitsunobu reaction conditions. The δ, ε-unsaturated cis-fused α-methylene γ-lactones (17, 18, and 25) thus prepared showed a moderate cytotoxic activity on P388 murine leukemia cells.

Conjugate Addition of Lithium Ester Enolates to 1‐Chlorovinyl p‐Tolyl Sulfoxides: A Novel Synthesis of Functionalized Esters and Lactones Having a Tertiary or a Quaternary Carbon at the β‐Position.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Conjugate addition of lithium ester enolates to 1-chlorovinyl p-tolyl sulfoxides: a novel synthesis of functionalized esters and lactones having a tertiary or a quaternary carbon at the β-position

Addition of the lithium ester enolates to 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from chloromethyl p-tolyl sulfoxide and ketones or aldehydes, gave esters having a tertiary or a quaternary carbon at the 3-position, and chlorine and sulfinyl groups at the 4-position in high to quantitative yields. The adducts were converted to various esters having methyl, formyl, and hydroxycarbonyl groups at the 3-position. A novel method for the synthesis of γ-lactones, including spiro-type γ-lactones and α-methylene γ-lactones, was realized from the adducts in good overall yields. The scope and limitations of this method and the mechanism of the reactions are also discussed.

Synthesis of optically active α-methylene γ-lactones through lipase-catalyzed kinetic resolution

The lipase-catalyzed kinetic resolution of the γ-hydroxy esters 1a,b and their subsequent acid-mediated cyclization afford the optically active α-methylene γ-lactones 2a,b in high yields (71–89%) and in up to 95% enantiomeric excess. The direct enzymatic lactonization of the racemic γ-hydroxy esters 1a,b to the lactones 2a,b represents a less satisfactory alternative, since poor enantioselectivies have been obtained.

Acryloxy and methacryloxy palladation of alkenes

Acrylic and methacrylic esters can be obtained in one step from alkenes using a Pd(OAc)2/benzoquinone/MnO2 catalyst; with acrylic acid and a suitable alkene, it is also possible to obtain α-methylene γ-lactones in one step.

Electrogenerated zinc as the catalyst in the allylation of carbonyl compounds direct synthesis of α-methylene-γ-lactones

The electroreduction of a catalytic amount of ZnBr 2 in acetonitrile provided a active Zn *, able to catalyze the reductive coupling of allyl bromides and chlorides with carbonyl compounds with high regioselectivity. Substituted α-methylene γ-lactones were obtained from functionalized allyl derivatives.

Optimization of the direct chiral separation of potential cytotoxic α-methylene-γ-butyrolactones and α-methylene-γ-butyrolactams by liquid chromatography

The direct enantiomeric resolution of a series of racemic α-methylene-γ-butyrolactones and α-methylene-γ-butyrolactams was carried out on various commercially available chiral stationary phases (CSPs). Particular interest was paid to compounds which exhibit physiological activity as cytotoxic agents. On a Pirkle-type column packed with ( R)-N-(3,5-dinitrobenzoyl)phenylglycine (DNBPG) covalently bonded to γ-aminopropylsilanized silica gel, only α-methylene-γ-lactams containing two aromatic groups were resolved; a chiral recognition mechanism is proposed. (+)-Poly-(triphenylmethyl methacrylate) (PTrMA) coated on silica gel [Chiralpak OT(+)] with methanol as eluent afforded fairly good selectivities (up to 1.8) especially for α-methylene γ-lactones. Temperature had a great influence on the resolution. Cellulose tribenzoate and triphenylcarbamate (Chiralcel OB and OC, respectively) coated on macroporous silica gel displayed selectivities from 1.1 to 1.3, but, because of the very poor efficiency of these CSPs, no baseline resolution was achieved. Investigations on two protein CSPs are reported, α 1-acid glycoprotein ( α 1-AGP) and bovine serum albumin (BSA) immobilized on microparticulate silica gel (Enantiopac and Resolvosil-BSA, respectively). The separations were performed using an aqueous sodium phosphate buffer as eluent and 2-propanol as organic modifier to regulate retention and selectivity. Both CSPs exhibited a good chiral recognition ability, especially towards cytotoxic solutes with resolution factors between 1 and 2.

ChemInform Abstract: Synthesis of Potential Cytotoxic α‐Methylene γ‐Lactams.

AbstractDie im Titel genannten Verbindungen (III) werden aus den Azomethinen (I) und dem Brommethyl‐acrylester (II) unter d‐en Bedingungen der Reformatskii‐Reaktion hergestellt.

Synthesis of Potential Cytotoxic α-Methylene γ-Lactams

Abstract α-Methylene γ-lactones are known to have physiological activity, especially as cytotoxic agents, and are widely found in nature (1). However they are often toxic which makes them inappropriate for cancer treatment.

Crystal and molecular structure of eupaformonin, a cytotoxic germacranolide from Eupatorium formosanum HAY

Single-crystal X-ray analysis has established the structure and relative stereochemistry of the title compound (I). The absolute configuration follows from the sign of the Cotton effect of then n→π* transition of the α-methylene γ-lactone CC–CO chromophore. Crystals are orthorhombic, space group P212121, a= 14.28(2), b= 11.52(2), c= 9.68(2)A, Z= 4. The structure was solved by direct phase-determining methods and atomic parameters refined by full-matrix least-squares calculations to R 0.093 over 1 437 reflections from photographic data. The Δ1(10)trans, Δ4cis-cyclodecadiene ring is in a chair, boat conformation with the C(4) and C(10) methyl groups oriented anti. The anomalous relationship between the sign of the measured Cotton effect of the CC–CO chromophore n→π* transition for Δ1(10)trans, Δ4cis germacranolide C(6), C(7)-trans-fused α-methylene γ-lactones and the position and stereochemistry of the lactone ring fusion is discussed with respect to the preferred cyclodecadiene ring conformation.

Sesquiterpenoids. Part XIV. X-Ray study of 13β-p-bromophenylthio-11α,13-dihydropulchellin-C diacetate (2α,3β-diacetoxy-13β-p-bromophenylthio-11α,13-dihydroisolantolactone): stereochemistry of addition of thiols to sesquiterpenoid α-methylene γ-lactones

The molecular structure of the p-bromobenzenethiol adduct of the sesquiterpenoid pulchellin-C diacetate (2α,3β-diacetoxyisolantolactone) has been determined by X-ray diffraction. In the formation of the adduct addition of the hydrogen atom to C(11) of the α-methylene γ-lactone took place cis to the hydrogen atom at C(8), causing the bulky RSCH2-group at C(11) to adopt a quasi-equatorial orientation on the envelope-like lactone ring. The cyclohexane ring A approximates closely to an ideal chair form with torsion angles in the range 56–62, mean 60°, but ring B, because of cis-fusion to the γ-lactone, is considerably distorted from ideal chair form and has torsion angles in the range 41–64, mean 51°. The adduct crystallizes in the orthorhombic space group P212121, with Z= 4, and a= 11·076(3), b= 7·194(2), c= 31·189(6)A. The structure was solved, from X-ray data measured on an automatic diffractometer, by Patterson and Fourier methods, and refined by least-squares techniques to R 6·0% for 1980 reflections. The absolute configuration of the sesquiterpenoid was established by the anomalous-dispersion effect.

A Simple Synthesis of α‐Methylene γ‐Lactones

Angewandte Chemie International Edition in EnglishVolume 9, Issue 6 p. 457-458 Communication A Simple Synthesis of α-Methylene γ-Lactones† Dr. Elisabeth Öhler, Dr. Elisabeth Öhler Organisch-Chemisches Institut der Universität, A-1090 Wien, Währingerstrasse 38 (Austria)Search for more papers by this authorKlaus Reininger, Klaus Reininger Organisch-Chemisches Institut der Universität, A-1090 Wien, Währingerstrasse 38 (Austria)Search for more papers by this authorProf. Dr. Ulrich Schmidt, Corresponding Author Prof. Dr. Ulrich Schmidt Organisch-Chemisches Institut der Universität, A-1090 Wien, Währingerstrasse 38 (Austria)Organisch-Chemisches Institut der Universität, A-1090 Wien, Währingerstrasse 38 (Austria)Search for more papers by this author Dr. Elisabeth Öhler, Dr. Elisabeth Öhler Organisch-Chemisches Institut der Universität, A-1090 Wien, Währingerstrasse 38 (Austria)Search for more papers by this authorKlaus Reininger, Klaus Reininger Organisch-Chemisches Institut der Universität, A-1090 Wien, Währingerstrasse 38 (Austria)Search for more papers by this authorProf. Dr. Ulrich Schmidt, Corresponding Author Prof. Dr. Ulrich Schmidt Organisch-Chemisches Institut der Universität, A-1090 Wien, Währingerstrasse 38 (Austria)Organisch-Chemisches Institut der Universität, A-1090 Wien, Währingerstrasse 38 (Austria)Search for more papers by this author First published: June 1970 https://doi.org/10.1002/anie.197004571Citations: 74 † Dedicated to Professor O. Hromatka on the occasion of his 65th birthday AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume9, Issue6June 1970Pages 457-458 RelatedInformation