Sequence Isomers Research Articles

Ring-closing metathesis for the synthesis of substituted indenols, indenones, indanones and indenes: Tandem RCM-dehydrogenative oxidation and RCM-formal redox isomerization

A number of substituted indenols have been synthesized using ruthenium-mediated ring-closing metathesis (RCM) with Grubbs second generation catalyst as the key step. The required dienes were synthesized by two strategies. The first entailed the isomerization of 2-allyl-3-isopropoxy-4-methoxybenzaldehyde to its styrene derivative, isopropoxy-4-methoxy-2-propenylbenzaldehyde using [RuClH(CO)(PPh 3) 3]. This compound and 3-isopropoxy-4-methoxy-2-(1-phenyl-propenyl)-benzaldehyde were then treated with vinyl- or isopropenyl-magnesium bromide to afford four of the scaffolds required for the metathesis. As the compound 3-isopropoxy-4-methoxy-2-(1-methyl-2-propenyl)benzaldehyde proved to be difficult to isomerize, the diene substrates 1-[3-isopropoxy-4-methoxy-2-(1-methylpropenyl)-phenyl]-prop-2-en-1-ol and 1-[3-isopropoxy-4-methoxy-2-(1-methylpropenyl)-phenyl]-2-methylprop-2-en-1-ol were synthesized by the addition of the Grignard reagents to 3-isopropoxy-4-methoxy-2-(1-methyl-2-propenyl)benzaldehyde, followed by isomerization of the arylallyl group to the thermodynamically favoured isomer with potassium t-butoxide. The use of harsher conditions (higher temperature and catalyst loadings) for the metathesis reactions resulted in the formation of substituted indenones, formed by a tandem RCM-dehydrogenative oxidation in the absence of a hydrogen acceptor. Further manipulations of the reaction conditions generated two substituted indanones by way of a tandem RCM-formal redox isomerization sequence. Finally the synthesis of some substituted indenes was accomplished from their corresponding dienes by the use of RCM.

A Concise Synthesis of (‐)‐Centrolobine via a Diastereoselective Ring Rearrangement Metathesis—Isomerization Sequence.

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, please click on HTML or PDF.

(Tetramethylcyclobutadiene)cobalt Complexes with Tricarbollide Ligands (Eur. J. Inorg. Chem. 9/2006)

AbstractThe cover picture shows the isomerization sequence of cobaltatricarbollides (C4Me4)Co(C3B8H11) prepared by using convenient synthons of the (C4Me4)Co fragment. The isomerization is associated with progressive space separation of the negatively charged carbon atoms and correlates well with the calculated relative stabilities of non‐methylated analogs. Introduction of an amino substituent at the cage carbon atom dramatically reduces the rearrangement barrier and changes the pathway of the process. Details are discussed in the article by A. R. Kudinov et al. on p. 1737 ff.

Gas‐chromatographic separation of stereoisomers of dipeptides

Synthetic dipeptides comprising mixtures of enantiomers, diastereomers, or sequential isomers were converted into their N-perfluoroacetyl dipeptide esters (perfluoroacetyl: trifluoroacetyl, pentafluoroacetyl, heptafluorobutyryl; ester: methyl, 1-propyl, 2-propyl, 2,2,2-trifluoroethyl) and analyzed by GC-MS on the chiral stationary phases Chirasil-L-Val and Lipodex-E using helium as carrier gas. Further, dipeptides were converted into their N-trifluoroacetyl dipeptide S-(+)-2-butyl esters and separated on achiral phenylmethyl polysiloxane column (HP-5 MS). Derivatization of dipeptides was performed at ambient temperature in order to avoid formation of the corresponding diketopiperazines. The best separation of stereoisomers was achieved with TFA and PFP methyl esters on Chirasil-L-Val.

Connecting catalytic cycles by organometallic transformations in situ: Novel perspectives in the olefin metathesis field

Abstract Tandem sequences consisting of an olefin metathesis step and a subsequent non-metathesis reaction become accessible by organometallic transformations of the Ru-carbene species in situ. This contribution highlights some tandem sequences that rely on the conversion of the metathesis catalyst to Ru-hydrides, with special emphasis on the tandem ring-closing metathesis (RCM)-double-bond isomerization sequence.

Unusual chromatographic behavior of oligonucleotide sequence isomers on two different anion exchange HPLC columns

The retention behavior of the unmodified phosphodiester oligonucleotide sequence isomers was investigated on two different anion exchange columns: Biospher GMB 1000Q (based on DEAE-modified glycidyl methacrylate) and PolyWAX LP (based on silica with a crosslinked coating of linear polyethyleneimine). There was a notable difference in retention of oligonucleotides of the same composition but differing in the position of a single base. The most pronounced difference was observed between the oligonucleotides with the variable base in the end and in the center of the sequence. The use of either acetonitrile or 2-propanol as a mobile phase organic modifier did not markedly affect the retention time patterns. Prediction of the retention times of oligonucleotides must take into account the base position as well as identity. This is the first report of such a “same composition different sequence” effect, described for the short peptides, for synthetic oligonucleotides.

Determination of Sequence-Specific Intrinsic Size Parameters from Cross Sections for 162 Tripeptides

Ion mobility and mass spectrometry techniques have been used to measure cross sections for 162 tripeptide sequences (27 different sets of six sequence isomers). The isomers have the general forms ABC, ACB, BAC, BCA, CAB, and CBA, where A corresponds to the amino acids Asp, Glu, or Gly, B corresponds to Lys, Arg, or Leu, and C corresponds to Phe, Tyr, or Ser. From these data, we derive a set of size parameters for individual amino acids that reflect the position of the amino acid in the sequence. These sequence-specific intrinsic size parameters (SSISPs) are used to retrodict cross-section values for the 162 measured sequences and to predict cross sections for all remaining tripeptide sequences (567 different sequences) that are comprised of these residues. In several types of peptide compositions, the position of the amino acid in the sequence has a significant impact on the parameter that is derived. For example, the sequence-specific intrinsic size parameter for leucine in the third position of a peptide (SSISP(Leu3)) is approximately 10% larger than SSISP(Leu1). On average, cross sections that are derived using SSISPs provide a better representation of the experimental value than those derived from composition only intrinsic size parameters, derived as described previously (Valentine et al. J. Phys. Chem. 1999, 103, 1203). Finally, molecular modeling techniques are used to derive some insight into the origin of cross-section differences that arise from sequence variation.

Coupling–Isomerization–Enamine Addition–Cyclocondensation Sequences:A Multicomponent Approach to Substituted and Annelated Pyridines

AbstractAnnelated (dihydropyridines, tetrahydroquinolines, naphthyridines) and substituted pyridines can be synthesized in moderate to good yields in a consecutive one‐pot, four‐component process by a coupling–isomerization–enamine addition–cyclocondensation sequence of an electron poor (hetero)aryl halide, a terminal propargyl alcohol, an enamine, and ammonium chloride. After the coupling–isomerization sequence a Diels–Alder reaction with inverse electron demand of the intermediate chalcone and the enamine furnishes a cycloadduct 6 that was unambiguously characterized by X‐ray structure analysis as well as the 1,5‐diketones 4b and 4g — the corresponding hydrolysis products — and the pyridine derivatives 11e (dihydropyridine), 11i (tetrahydroquinoline), 11o (naphthyridine), and 14b and 14c (ethyl nicotinoates). Additionally, quantum chemical calculations support the stepwise nature of the enamine cycloaddition. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Ruthenium‐Catalyzed Olefin Metathesis Double‐Bond Isomerization Sequence.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Charge state-dependent fragmentation of oligonucleotide/metal complexes

Collision-activated dissociation (CAD) has been employed to assess the gas-phase fragmentation behavior of a series of 1:1 oligodeoxynucleotide (ODN):metal complexes over a range of charge states, using several ten-residue ODNs and a wide array of alkali, alkaline earth, and transition metals. For parent species in low to intermediate charge states, complexation with Ca(+2), Sr(+2), or Ba(+2) altered the relative intensity of M-B species, promoting loss of cytosine over loss of guanine. The relative intensities of sequence ions were largely unaffected. This behavior was most prevalent for isomeric sequences with complementary residues at the 5'- and 3'-termini, suggesting that metal complexation may change the gas-phase conformation and/or conformational dynamics for some sequences. In higher charge states, some ODN/Ba(+2) complexes produced abundant fragment ions corresponding to metallated a(n)(-m) species, which are not commonly observed in CAD mass spectra for deprotonated ODNs. The formation of these ions was most favored for complexes between Ba(+2) and ODN sequences with a thymine residue at Position 6. Literature precedent exists for the formation of a(n)(-m) ions from sequences in which covalent modification generates one or more neutral sites along the phosphate backbone. ODN/metal adducts in high charge states possess only a few acidic protons, and the juxtaposition of these neutral phosphate groups near thymine residues and the bound Ba(+2) ion may direct formation of the metallated a(n)(-m) species.

A Convenient Synthesis of 1,4‐Disubstituted Imidazoles.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Ruthenium-Catalyzed Olefin Metathesis Double-Bond Isomerization Sequence

A novel ruthenium-catalyzed tandem ring-closing metathesis (RCM) double-bond isomerization reaction is described in this paper. The utility of this method for the efficient syntheses of five-, six-, and seven-membered cyclic enol ethers is demonstrated. It relies on the conversion of a metathesis-active ruthenium carbene species to an isomerization-active ruthenium-hydride species in situ. This conversion is achieved by using various additives. Scope and limitations of the different protocols are discussed, and some mechanistic considerations based on (31)P and (1)H NMR spectroscopic studies are presented.

One-pot syntheses of dihydro benzo[ b][1,4]thiazepines and -diazepines via coupling–isomerization–cyclocondensation sequences

2,4-Di(hetero)aryl substituted 2,3-dihydro benzo[ b][1,4]heteroazepines 7 and 9 (hetero=S, NH) can be readily synthesized in a one-pot process initiated by a coupling–isomerization sequence of an electron poor (hetero)aryl halide 4 and a terminal propargyl alcohol 5 subsequently followed by a cyclocondensation with 2-mercapto or 2-amino anilines 6 or 8 , respectively. In addition, the structures were established unambiguously by an X-ray structure analysis of 9b .

Synthesis, Characterization, and Evaluation as Emulsifiers of Amphiphilic−Ionizable Aromatic Methacrylate ABC Triblock Terpolymers

Four isomeric terpolymers based on benzyl methacrylate (BzMA, nonionic hydrophobic), 2-(dimethylamino)ethyl methacrylate (DMAEMA, ionizable hydrophilic), and methoxyhexa(ethylene glycol) methacrylate (HEGMA, nonionic hydrophilic) were synthesized using group transfer polymerization (GTP). The three of the terpolymers were the ABC block sequence isomers, ABC, ACB, and BAC, and the fourth was the statistical terpolymer. Their theoretical molecular weight was 5000 g mol-1, and the theoretical w/w composition was 33% from each monomer. The success of the synthesis was confirmed by gel permeation chromatography (GPC), which showed that the experimental molecular weights were in reasonable agreement with the theoretical ones and the polydispersity indices were low (in most cases <1.1), and by proton nuclear magnetic resonance (1H NMR) spectroscopy, which provided experimental compositions very close to the theoretical ones. All the terpolymers were characterized in aqueous solution by dynamic light scattering a...

A convenient synthesis of 1,4-disubstituted imidazoles

An efficient method for the regioselective protection of 4-alkyl-, 4-iodo, 4-vinylimidazoles has been developed via an alkylation–isomerization sequence with various imidazole-protecting groups. The initially formed mixture of 4/5-alkyl-, 4/5-iodo, and 4/5-vinylimidazoles are isomerized to the corresponding 4-isomers on treatment of a DMF solution with a small amount of RX and heating at 75°C.

Sequence-dependent bending in plasmid pUC19.

The circular permutation assay has been used to characterize sequence-dependent bending in plasmid pUC19 (2686 bp). Linear, permuted sequence isomers of pUC19 exhibit different mobilities in large-pore polyacrylamide gels, suggesting that the plasmid contains two sequence-dependent bends, one located at approximately 806 bp, close to the start site of transcription, and the other at approximately 2617 bp, near the promoter of the ampicillin resistance gene. The mobility patterns are independent of the buffer in which the gels are cast and run, independent of pH over the range 6.5-8.6, and independent of the presence or absence of various monovalent ions added to the buffer, suggesting that the maxima in the mobility patterns correspond to stable bends in the helix backbone, not anisometric flexibility. Although the mobility patterns are unchanged when Ba(++) or Zn(++) ions are added to the buffer, several of the sequence isomers exhibit multiple sharp sub-bands in solutions containing Mg(++) or Ca(++) ions, indicating the presence of multiple conformational isomers. In addition, the mobility maximum near the start site of transcription is shifted by approximately 100 bp in the presence of Ca(++) ions, suggesting that the location of the actual bend center is somewhat variable, depending on the ionic composition of the surrounding medium. The number of maxima observed in the mobility pattern can be increased by adding a bend from another plasmid, such as Litmus 28; the number of maxima can be decreased by removing one of the bends in pUC19 by restriction enzyme digestion and religation. Hence, the number of maxima in the mobility pattern is an accurate indication of the number of stable, sequence-dependent bends present in the plasmid. The combined results indicate that the circular permutation assay in large-pore polyacrylamide gels is a reliable method of detecting and analyzing sequence-dependent bends in kilobase-sized DNA molecules.

Probing helix formation in unsolvated peptides.

Ion mobility measurements have been used to examine helix formation in unsolvated glycine-based peptides containing three alanine residues. Nine sequence isomers of Ac-[12G3A]K+H(+) were studied (Ac = acetyl, G = glycine, A = alanine, and K = lysine). The amount of helix present for each peptide was examined using two metrics, and it is strongly dependent on the proximity and the location of the alanine residues. Peptides with three adjacent alanines have the highest helix abundances, and those with well-separated alanines have the lowest. The helix abundances for most of the peptides can be fit reasonably well using a modified Lifson-Roig theory. However, Lifson-Roig theory fails to account for several key features of the experimental results. The most likely explanation for the correlation between helix abundances and the number of adjacent alanines is that neighboring alanines promote helix nucleation.

A Highly Selective Route to β‐C‐Glycosides via Nonselective Samarium Iodide Induced Coupling Reactions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

An Olefin Metathesis/Double Bond Isomerization Sequence Catalyzed by an in situ Generated Ruthenium Hydride Species.

AbstractFor Abstract see ChemInform Abstract in Full Text.

New Tandem Catalysis: Preparation of Cyclic Enol Ethers Through a Ruthenium‐Catalyzed Ring‐Closing Metathesis—Olefin Isomerization Sequence.

Tandem reactions that proceed with a single metal catalyst precursor offer novel opportunities for developing efficient new reaction sequences. In this regard, reaction conditions have been identified that allows for a tandem ring-closing metathesis−olefin isomerization sequence catalyzed by a common ruthenium precursor. Specifically, the tandem process generates cyclic enol ethers from a variety of readily available acyclic dienes in a single reaction vessel using Grubbs' ruthenium alkylidene.