Exo-methylene Group Research Articles

Synthesis of novel 2,6-disubstituted-3,4-dimethylidene tetrahydropyrans via Prins-type cyclization.

Synthesis of novel substituted tetrahydropyrans with adjacent exo-methylene groups at the C3 and C4 positions via Prins-type cyclization has been described.

Rotation of the exo-methylene group of (R)-3-methylitaconate catalyzed by coenzyme B(12)-dependent 2-methyleneglutarate mutase from Eubacterium barkeri.

2-Methyleneglutarate mutase from the anaerobe Eubacterium (Clostridium) barkeri is an adenosylcobalamin (coenzyme B(12))-dependent enzyme that catalyzes the equilibration of 2-methyleneglutarate with (R)-3-methylitaconate. Two possibilities for the mechanism of the carbon skeleton rearrangement of the substrate-derived radical to the product-related radical are considered. In both mechanisms an acrylate group migrates from C-3 of 2-methyleneglutarate to C-4. In the "addition-elimination" mechanism this 1,2-shift occurs via an intermediate, a 1-methylenecyclopropane-1,2-dicarboxylate radical, in which the migrating acrylate is simultaneously attached to both C-3 and C-4. In the "fragmentation-recombination" mechanism the migrating group, a 2-acrylyl radical, becomes detached from C-3 before it starts bonding to C-4. In an attempt to distinguish between these two possibilities we have investigated the action of 2-methyleneglutarate mutase on the stereospecifically deuterated substrates (Z)-3-methyl[2'-(2)H(1)]itaconate and (Z)-3-[2'-(2)H(1),methyl-(2)H(3)]methylitaconate. The enzyme catalyzes the equilibration of both compounds with their corresponding E-isomers and with a 1:1 mixture of the corresponding (E)- and (Z)-2-methylene[2'-(2)H(1)]glutarates, as shown by monitoring of the reactions with (1)H and (2)H NMR. In the initial phase of the enzyme-catalyzed equilibration a significant excess (8-11%) of (E)-3-methyl[2'-(2)H(1)]itaconate over its equilibrium value was observed ("E-overshoot"). The E-overshoot was only 3-4% with (Z)-3-[2'-(2)H(1),methyl-(2)H(3)]methylitaconate because the presence of the deuterated methyl group raises the energy barrier from 3-methylitaconate to the corresponding radical. The overshoot is explained by postulating that the migrating acrylate group has to overcome an additional energy barrier from the state leading back to the substrate-derived radical to the state leading forward to the product-related radical. It is concluded that the fragmentation-recombination mechanism can provide an explanation for the results in terms of an additional energy barrier, despite the higher calculated activation energy for this pathway.

Synthesis of a compound having the essential structural unit for the hetisine-type of aconite alkaloids

A hexacyclic compound 1 , which carries an almost full structure of the hetisine skeleton lacking only the six-membered ring with an exo methylene group, was synthesized by applying an acetal-ene reaction on 5 for the bond formation of C-14 and C-20 as well as stereoselective hydrocyanation reaction on 7 for construction of the azabicyclo ring system.

A novel reaction between adenosylcobalamin and 2-methyleneglutarate catalyzed by glutamate mutase.

We describe a novel reaction of adenosylcobalamin that occurs when adenosylcobalamin-dependent glutamate mutase is reacted with the substrate analogue 2-methyleneglutarate. Although 2-methyleneglutarate is a substrate for the closely related adenosylcobalamin-dependent enzyme 2-methyleneglutarate mutase, it reacts with glutamate mutase to cause time-dependent inhibition of the enzyme. Binding of 2-methyleneglutarate to glutamate mutase initiates homolysis of adenosylcobalamin. However, instead of the adenosyl radical proceeding to abstract a hydrogen from the substrate, which is the next step in all adenosylcobalamin-dependent enzymes, the adenosyl radical undergoes addition to the exo-methylene group to generate a tertiary radical at C-2 of methyleneglutarate. This radical has been characterized by EPR spectroscopy with regiospecifically (13)C-labeled methyleneglutarates. Irreversible inhibition of the enzyme appears to be a complicated process, and the detailed chemical and kinetic mechanism remains to be elucidated. The kinetics of this process suggest that cob(II)alamin may reduce the enzyme-bound organic radical so that stable adducts between the adenosyl moiety of the coenzyme and 2-methyleneglutarate are formed.

Structure and Reactivity of (η3-Indolylmethyl)palladium Complexes Generated by the Reaction of Organopalladium Complexes with o-Alkenylphenyl Isocyanide

The reaction of methylpalladium complexes with o-alkenylphenyl isocyanides results in the successive intramolecular insertion of the alkenyl and isocyano groups followed by the 1,3-migration of hydrogen to give (η3-indolylmethyl)palladium complexes (4) in good yields. Treatment of 4 with diethylamine causes nucleophilic attack at the exo methylene carbon to give 2-methyl-3-(aminomethyl)indole, whereas the reactions with HCl produce 2,3-dimethylindole derivatives.

Characterization of CO2 Plasma and Interactions with Polypropylene Film

The interactions between CO2 plasma, less degrading than O2 plasma, and polymeric surfaces are studied. CO2 discharge and the relationships between the density of plasma reactive species are analyzed by optical emission spectroscopy and mass spectrometry. The optical emission spectrum was identified and five principal systems of carbon monoxide were assigned: the 4th and 3rd positive systems, Angstrom and 3A systems. Other systems dealing with ionized species CO+2 and CO+ were also found. Mass spectrometry showed that the carbon monoxide and atomic oxygen were created through CO2 dissociation by electronic impact. The detected molecular oxygen coming from the atomic oxygen recombination was associated with the power. The study of plasma/polymer interface showed the consumption of ionized species, the appearance of atomic hydrogen due to methyl groups transformation into exomethylene groups onto the polypropylene surface, and a degradation mechanism dependent on atomic oxygen density in the plasma phase.

A Synthesis of Demethyl Mycosporulone and its C-6 Epimer

Demethyl mycosporulone was synthesized from the methyl ester of dihydro anisic acid in six steps. The key steps included an aldol/oxidation sequence and the formation of the exomethylene group by dehydration using Burgesssalt.

Studies on the inactivation of bovine liver enoyl-CoA hydratase by (methylenecyclopropyl)formyl-CoA: elucidation of the inactivation mechanism and identification of cysteine-114 as the entrapped nucleophile.

The inhibitory properties of (methylenecyclopropyl)formyl-CoA (MCPF-CoA), a metabolite derived from a natural amino acid, (methylenecyclopropyl)glycine, against bovine liver enoyl-CoA hydratase (ECH) were characterized. We have previously demonstrated that MCPF-CoA specifically targets ECHs, which catalyze the reversible hydration of alpha,beta-unsaturated enoyl-CoA substrates to the corresponding beta-hydroxyacyl-CoA products. Here, we synthesized (R)- and (S)-diastereomers of MCPF-CoA to examine the stereoselectivity of this inactivation. Both compounds were shown to be competent inhibitors for bovine liver ECH with nearly identical second-order inactivation rate constants (k(inact)/K(I)) and partition ratios (k(cat)/k(inact)), indicating that the inactivation is nonstereospecific with respect to ring cleavage. The inhibitor, upon incubation with bovine liver ECH, labels a tryptic peptide, ALGGGXEL, near the active site of the protein, where X is the amino acid that is covalently modified. Cloning and sequence analysis of bovine liver ECH gene revealed the identity of the amino acid residue entrapped by MCPF-CoA as Cys-114 (mature sequence numbering). On the basis of gHMQC (gradient heteronuclear multiple quantum coherence) analysis with [3-(13)C]-labeled MCPF-CoA, the ring cleavage is most likely induced by the nucleophilic attack at the terminal carbon of the exomethylene group (C(2)'). We propose a plausible inactivation mechanism that involves relief of ring strain and is consistent with examples found in the literature. In addition, these studies provide important clues for future design of more efficient and selective inhibitors to control and/or regulate fatty acid metabolism.

Selective radical synthesis of β-C-disaccharides

Several β-C-disaccharides have been selectively synthesized by radical cyclization of two temporarily tethered functionalized monosaccharides. In this process, intramolecular addition of a carbohydrate-derived radical onto an anomeric exomethylene group, followed by axial hydrogen addition, resulted in β stereochemistry.

Chemoselective Ring-Opening Polymerization of a Lactone Having exo-Methylene Group with Lipase Catalysis

Chemoselective Ring-Opening Polymerization of a Lactone Having <i>e</i><i>xo</i>-Methylene Group with Lipase Catalysis

ChemInform Abstract: Diastereoselective Synthesis of Hydantoin- and Isoxazoline-Substituted Dispirocyclobutanoids.

Synthetic strategies for constructing novel achiral cyclobutanoid isoxazolidinoimidazolidinedione heterocycles, with a generalized structure of II, have been developed via 1,3-dipolar cycloaddition and carbanilide cyclization transformations from methylenecyclobutane 13. The exo methylene cyclobutane system has made the realization of some diasteroselectivity possible, such that the H-bond (Boc-NH) directed product (i.e., 14) was obtained with 3:1 selectivity relative to the non-H-bond directed product (i.e., 15).

Nazarov Cyclization of 4-Cycloalkylidene-5-(trimethylsilyl)pent-1-en-3-one Derivatives. Synthesis of Spiro[4.5]decane, Spiro[4.4]nonane, and Their Derivatives

Spiro[4.5]decane and spiro[4.4]nonane ring systems were synthesized by FeCl 3-induced Nazarov cyclization of α-(trimethylsilylmethyl)divinyl ketone derivatives. It was found that the double bond position of the product is controlled by the presence/absence of α′-substituent, while trimethylsilyl group is essential to obtain the products in good yields. Spiro[4.4]nonanes having exo-methylene group underwent rearrangement to bicyclo[4.3.0]nonanes.

Diastereoselective synthesis of hydantoin- and isoxazoline-substituted dispirocyclobutanoids.

Synthetic strategies for constructing novel achiral cyclobutanoid isoxazolidinoimidazolidinedione heterocycles, with a generalized structure of II, have been developed via 1,3-dipolar cycloaddition and carbanilide cyclization transformations from methylenecyclobutane 13. The exo methylene cyclobutane system has made the realization of some diasteroselectivity possible, such that the H-bond (Boc-NH) directed product (i.e., 14) was obtained with 3:1 selectivity relative to the non-H-bond directed product (i.e., 15).

Induction of choline acetyltransferase activity in cholinergic neurons by stolonidiol: structure-activity relationship.

The effect of stolonidiol (1), a bioactive marine diterpenoid from the Japanese soft coral Clavularia sp., on choline acetyltransferase (ChAT) activity was examined using cultured cholinergic neurons. Stolonidiol (1) showed potent ChAT inducible activity in primary cultured basal forebrain cells and clonal septal SN49 cells, suggesting that it may act as a potent neurotrophic factor-like agent on the cholinergic nervous system. Further expansion of the structure-activity relationship to include stolonidiol (1) and its derivatives demonstrated that the exo-methylene group and the epoxide group are essential for ChAT-inducing activity. Stolonidiol (1) showed the highest activity among the test samples.

Thiol Gel as a Matrix for Binding-Release of α,β-Unsaturated Sesquiterpene Lactones

The hydrogel thiopropyl-sepharose 6B was used as a model matrix system to bind the natural cytotoxic sesquiterpene lactones grosheimin 1 and deacylcynaropicrin 2. The hydrogel thio groups were bonded to the lactone exomethylene groups and the release of the lactones from the polymer was studied. Since it is thought that cancer cells have a higher oxidative potential than normal cells, the release was carried out through an oxidative cleavage. Different concentrations of hydrogen peroxide solutions were added to the lactone-polymer conjugates, thus, imitating in vivo conditions. The results obtained showed that both the rate and amount of grosheimin and deacylcynaropicrin release depend linearly on the H2O2 concentration.

Formation of a Palladalactone Complex by C–O Bond Cleavage of Diketene Promoted by a Zerovalent Palladium Complex

Abstract The reaction of diketene with [Pd(PMe3)2(styrene)] 1 at room temperature gave ([Pd(OCOCH2C=CH2)(PMe3)2]) 2 through cleavage of the C–O bond adjacent to the carbon bearing the exomethylene group. The structure of 2 was fully established by spectroscopic means, elemental analysis and single-crystal X-ray analysis. The reactivity of 2 has been investigated.

Cationic Ring-Opening Polymerization of an Exomethylene Group Carrying Cyclic Carbonate. Pseudo-Living Polymerization of 5-Methylene-1,3-dioxan-2-one by the Assistance of the Exomethylene Group

Cationic ring-opening polymerization of a cyclic carbonate carrying an exomethylene moiety, 5-methylene-1,3-dioxan-2-one (ExTMC), was carried out, and its behavior was compared with a cyclic carbonate having no exomethylene group, 1,3-dioxan-2-one (TMC). ExTMC afforded the polymers with larger molecular weights than TMC under any conditions. The observed molecular weights of the polymers agreed well with the calculated ones in the polymerization of ExTMC with TfOH at 0 °C. A linear relationship was observed between the conversion and number-average molecular weight of the polymer obtained in the polymerization of ExTMC, which could not be observed in the polymerization of TMC. After ExTMC was completely converted, the polymerization took place again when the same amount of ExTMC was introduced into the polymerization mixture. The effect of the exomethylene group on the polymerization behavior was analyzed by an ab initio molecular orbital calculation to determine the possibility of the presence of an ally...

ChemInform Abstract: Selective Reduction of the Exomethylene Group of α‐Methylene γ‐ or δ‐Lactones with CdCl2—Mg—MeOH—H2O.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Ring-opening polymerization of heterocycles bearing substituted and unsubstituted exo-methylene groups - a review

Monocyclic monomers bearing exo-methylene groups are likely to undergo ring-opening polymerization under the conditions of radical or cationic initiation. Several structural features will determine the course of reaction after initiation by species that exclusively attack the exo-methylene functionality. Reviewing some of the most common classes of monocyclic heterocycles it becomes obvious that a monomer has to meet certain structural preconditions that makes them suitable for isomerizations. Among the considered heterocycles there are some types of monomers possessing an outstanding ring-opening behavior following polymerization mechanisms free from side-reactions. The combination of strain release due to ring-opening isomerization, an energy decrease in the transition state caused by the formation of carbonyl-functionalities and an appropriate stabilization of the growing chain end by steric and electronic effects may lead to clear ring-opening mechanisms. However, this property remains restricted to only some special monomers with simple aromatic substituents being attached to the cycle. Hence a variety of cyclic ketene acetals, enolethers, (meth)acrylates, carbonates, lactones and lactames have been chosen in order to demonstrate both the possibilities and limits of ring-opening.

Addition and Ring Expansion Reactions of Tricarbonyl(1,2-dioxobenzocyclobutene)chromium(0) with Carbon Nucleophiles – Unexpected Formation of Benzocycloheptene Derivatives and the First Head-to-Head Coupling of Two Methoxyallene Molecules

Addition of carbon nucleophiles to (benzocyclobutenedione)tricarbonylchromium(0) (4) results in the formation of exo mono- and diadducts as well as 1,2-diketones as the consequence of proximal ring-opening reactions. In one case the unexpected formation of benzocycloheptenedione complexes is observed. Treatment of 4 with an excess of 1-ethoxy-1-lithioethene gives the product of a dianionic oxy-Cope rearrangement followed by an intramolecular aldol addition. This is also the case with lithiated methoxyallene, and as the result the first head-to-head coupling product 12 of two methoxyallene molecules is isolated in good yield. 12 is used as a diene in Diels-Alder cycloadditions, and its molecular structure is compared to that of the similar molecule 13, lacking the two exo methylene substitutents.