Elusive Isomer Research Articles

Biosynthesis of Menaquinone in E. coli: Identification of an Elusive Isomer of SEPHCHC.

In the biosynthesis of menaquinone in bacteria, the thiamine diphosphate‐dependent enzyme MenD catalyzes the decarboxylative carboligation of α‐ketoglutarate and isochorismate to (1R,2S,5S,6S)‐2‐succinyl‐5‐enolpyruvyl‐6‐hydroxycyclohex‐3‐ene‐1‐carboxylate (SEPHCHC). The regioisomer of SEPHCHC, namely (1R,5S,6S)‐2‐succinyl‐5‐enolpyruvyl‐6‐hydroxycyclohex‐2‐ene‐1‐carboxylate (iso‐SEPHCHC), has been considered as a possible product, however, its existence has been doubtful due to a spontaneous elimination of pyruvate from SEPHCHC to 2‐succinyl‐6‐hydroxy‐2,4‐cyclohexadiene‐1‐carboxylate (SHCHC). In this work, the regioisomer iso‐SEPHCHC was distinguished from SEPHCHC by liquid chromatography‐tandem mass spectrometry. Iso‐SEPHCHC was purified and identified by NMR spectroscopy. Just as SEPHCHC remained hidden as a MenD product for more than two decades, its regioisomer iso‐SEPHCHC has remained until now.

Asymmetric Synthesis of Fluoro, Fluoromethyl, Difluoromethyl, and Trifluoromethylcyclopropanes.

Fluorine-containing cyclopropanes are a subclass of cyclopropane derivatives that have generated considerable interest in medicinal chemistry for several decades. The replacement of a cyclopropane C-H or C-CH3 bond with fluorine or a fluorinated group (such as CF3 or CF2H) can lead sometimes to synergistic effects in terms of biological activity and improved metabolic profile of a cyclopropane containing bioactive compound. In this context, the preparation of fluoro-, difluoromethyl-, or trifluoromethyl-cyclopropane is particularly attractive and important but quite challenging considering the unique electronic properties that result from the incorporation of a fluorine atom into a substrate or a reagent. In the past decade, we have sought to develop new routes for the stereoselective synthesis of these building blocks using the most reliable cyclopropanation methods and convenient and readily available starting materials. The challenge that had to be undertaken was how we could use the unique properties of the fluorine atom to improve upon the efficiency of a given process rather than shutting it down. This could be overcome by defining new substrate/reagent reactivity guidelines and carefully selecting whether the fluorinated group was introduced on the electrophilic or nucleophilic partner for a given reaction. In this Account, we describe our contributions in this area that take advantage of diazo-derived rhodium carbenes, zinc carbenoids, ring closure processes, and biocatalytic methods to access these important potential drug subunits. Our initial investigation relied on the development of a Michael-initiated ring closure reaction using the Reformatsky enolate derived from readily available ethyl dibromofluoroacetate and α,β-unsaturated electrophiles. The reaction proceeded extremely well but with modest to good diastereoselectivities with ester acrylates. Further extension to various fluorinated nucleophiles such as oxazolidinone based and DABCO ylides led to similar selectivities.In order to access enantioenriched fluorocyclopropanes, we then investigated the chiral dioxaborolane mediated zinc carbenoid based approaches using the fluoroiodomethylzinc carbenoid/allylic alcohol combination or the iodomethylzinc carbenoid/fluoroallylic alcohol combination. Quite surprisingly, both approaches were equally successful at providing the corresponding fluorocyclopropanes with excellent diastereo- and enantioselectivities.To broaden the scope of fluorinated cyclopropane building blocks that could be prepared with good enantiocontrol, we then investigated the rhodium-catalyzed cyclopropanation of fluoro-, difluoromethyl-, and trifluoromethyl-substituted alkenes with acceptor-acceptor and donor-acceptor diazo reagents. Depending on the substrate/reagent combination, Hashimoto's Rh2((S)-TCPTTL)4 or Davies' Rh2((S)-BTPCP)4 catalyst proved be the most efficient catalysts providing the cyclopropane derivatives with the highest enantioselectivities.More recently, a collaboration with Fasan's group led to the use of engineered myoglobins to catalyze the reaction of ethyl diazoacetate and difluoromethyl-substituted alkenes. This biocatalyzed process led to high turnover number and high enantioselectivities.Although our work has significantly increased the number of tools in the organic chemist's toolbox, continuous efforts in this area would be beneficial to the development of diastereo- and enantioselective approaches to allow the preparation of any elusive isomers of these valuable chiral building blocks.

Configurational Isomerism in Polyoxovanadates.

A water-soluble derivative of the polyoxovanadate {V15 E6 O42 } (E=semimetal) archetype enables the study of cluster shell rearrangements driven by supramolecular interactions. A reaction unique to E=Sb, induced exclusively by ligand metathesis in peripheral [Ni(ethylenediamine)3 ]2+ counterions, results in the formation of the metastable α1 * configurational isomer of the {V14 Sb8 O42 } cluster type. Contrary to all other polyoxovanadate shell architectures, this isomer comprises an inward-oriented vanadyl group and is ca. 50 and 12 kJ mol-1 higher in energy than the previously isolated α and β isomers, respectively. We discuss this unexpected reaction in light of supramolecular Sb-O⋅⋅⋅V and Sb-O⋅⋅⋅Sb contacts manifested in {V14 Sb8 O42 }2 dimers detected in the solid state. ESI MS experiments confirm the stability of these dimers also in solution and in the gas phase. DFT calculations indicate that other, as of yet elusive isomers of {V14 Sb8 }, might be accessible as well.

Studying Gas-Phase Interconversion of Tautomers Using Differential Mobility Spectrometry.

In this study, we report on the use of differential mobility spectrometry (DMS) as a tool for studying tautomeric species, allowing a more in-depth interrogation of these elusive isomers using ion/molecule reactions and tandem mass spectrometry. As an example, we revisit a case study in which gas-phase hydrogen-deuterium exchange (HDX)-a probe of ion structure in mass spectrometry-actually altered analyte ion structure by tautomerization. For the N- and O-protonated tautomers of 4-aminobenzoic acid, when separated using DMS and subjected to subsequent HDX with trace levels of D2O, the anticipated difference between the exchange rates of the two tautomers is observed. However, when using higher levels of D2O or a more basic reagent, equivalent and almost complete exchange of all labile protons is observed. This second observation is a result of the interconversion of the N-protonated tautomer to the O-protonated form during HDX. We can monitor this transformation experimentally, with support from detailed molecular dynamics and electronic structure calculations. In fact, calculations suggest the onset of bulk solution phase properties for 4-aminobenzoic acid upon solvation with eight CH3OH molecules. These findings also underscore the need for choosing HDX reagents and conditions judiciously when separating interconvertible isomers using DMS. Graphical Abstract ᅟ.

Overcoming catalytic bias

Metathesis reactions can be used to make carbon–carbon double bonds — bar one isomeric class. By using new catalysts and balancing out the stabilities of intermediates in the reaction, the elusive isomers can be made. See Article p.461 The Z-alkene bond is one of the most important chemical bonds in nature. Many natural products contain one or several Z alkenes, consisting of a double bond with two substituents at each end pointing in the same direction. The potency or function of these natural products disappears or changes significantly if the two substituents point in opposite directions — a structure called an E alkene. Convenient methods for the stereoselective synthesis of 1,2-disubstituted Z alkenes are scarce. Amir Hoveyda and colleagues now describe catalytic Z-selective cross-metathesis reactions of terminal enol ethers and allylic amides, previously used only in E-selective processes. The potential of this reaction is demonstrated by its use in syntheses of antioxidant plasmalogen phospholipids found in electronically active tissues and implicated in Alzheimer's disease, and the potent immunostimulant and antitumour agent KRN7000.

An Epilogue on the C78‐Fullerene Family: The Discovery and Characterization of an Elusive Isomer

An Epilogue on the C₇₈‐Fullerene Family: The Discovery and Characterization of an Elusive Isomer

An Epilogue on the C78‐Fullerene Family: The Discovery and Characterization of an Elusive Isomer

An Epilogue on the C₇₈‐Fullerene Family: The Discovery and Characterization of an Elusive Isomer

ChemInform Abstract: An Epilogue on the C78‐Fullerene Family: The Discovery and Characterization of an Elusive Isomer.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 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.

An Epilogue on the C78-Fullerene Family: The Discovery and Characterization of an Elusive Isomer

Vermisste Verwandte: Das letzte Mitglied der ersten Fullerenfamilie, C78(4), konnte synthetisiert und isoliert werden. Das Verknüpfungsmuster wurde durch Einkristall-Röntgenstrukturanalyse des chlorierten Derivats C78(4)Cl18 nachgewiesen (siehe Bild). In der Kristallstruktur zeigten sich außerdem ungewöhnlich kurze intermolekulare Kontakte zwischen Chloratomen.

An Epilogue on the C78‐Fullerene Family: The Discovery and Characterization of an Elusive Isomer

An Epilogue on the C₇₈‐Fullerene Family: The Discovery and Characterization of an Elusive Isomer

Cyclopent[b,c]acenaphthylene: An elusive isomer of pyracylene with the ring currents of an annelated pentalene

Ab initio ipsocentric current–density mapping techniques are used to visualise the current density induced by a perpendicular magnetic field in the still unknown cyclopent[b,c]acenaphthylene (1). The π system divides into distinct, but contiguous, paratropic and diatropic regions, both supporting extended ring currents, the two currents running together along the pentagon–hexagon border. On the usual magnetic definition, cyclopent[b,c]acenaphthylene (1) is therefore part aromatic and part antiaromatic. Orbital analysis attributes the ring–current magnetic response of 1 to its eight most energetic π electrons. It is concluded that cyclopent[b,c]acenaphthylene (1) constitutes an ‘annelated pentalene’. This is supported by the computed 1H NMR chemical shifts of 1; they are all positioned upfield with respect to naphthalene (3).

Synthesis of [ethylene-1-(eta(5)-4,5,6,7-tetrahydro-1-indenyl)-2- (eta(5)-4',5',6',7'-tetrahydro-2'-indenyl)]titanium dichloride, the elusive isomer of the Brintzinger-type ansa-titanocenes.

We present a short synthesis of 1-(2-indenyl)-2-(3-indenyl)ethane (5) and a method for its conversion to the ansa-metallocene [ethylene(eta5-inden-1-yl)(eta5-inden-2-yl)]titanium dichloride (13). The synthetic strategy applied to prepare bisindene 5 relies on the efficient alkylation of 2-(phenylsulfonyl)indane followed by HMPA-assisted E1cB-elimination of phenylsulfinate. This tandem sequence circumvents the predisposition of indene to undergo C(1)-alkylation and enables access to C(2)-substituted indenes. The key step in the synthesis of the title ansa-titanocene (4) features a previously unreported equilibration step to generate the bis(indenide anion) of 5. Complexation with TiCl4.(THF)2 followed by hydrogenation of the product metallocene furnishes ansa-titanocene 4.

Structural characterisation of the elusive isomer of Os 3(CO) 10(PPh 3) 2

The X-ray crystal structure of the elusive isomer of Os 3(CO) 10(PPh 3) 2 in which the two phosphine ligands are cis and trans with respect to the phosphine-substituted Os–Os edge has been determined; the first direct confirmation for the existence of this isomer in Os 3(CO) 10(PR 3) 2 clusters. In contrast to the trans,trans isomer, the cis,trans isomer shows little twisting of the Os(CO) 3(PPh 3) groupings with respect to the Os(CO) 4 unit.