Ring Opening Of Cis Research Articles

Enantioselective Ring Opening Reactions of Azabenzonorbornadienes with Carboxylic Acids

AbstractThe palladium/silver (Pd/Ag) co‐catalytic system was found to be effective for the enantioselective ring opening reactions of the low reactive azabenzonorbornadienes with weak nucleophilic carboxylic acids. Both aryl and alkyl carboxylic acids are suitable nucleophiles and afforded the cis ring opening products in good yields with excellent enantioselectivities. The absolute configuration of one of the products has been confirmed by X‐ray crystal structure analysis, and a plausible reaction pathway is proposed.magnified image

Formation of heterobinuclear Pt–Au complexes by chelate ring-opening of cis-[Pt(κ2-C6R4PPh2)2] (R = H, F)

Mixed metal complexes of the type [Pt(κ2-2-C6R4PPh2) (PPh3) (μ-2-C6R4PPh2)AuCl] (R = H, F) can be prepared by treatment of cis-[Pt(κ2-C6R4PPh2)2] with [AuCl(PPh3)]. Under similar reaction conditions, the trans isomer of [Pt(κ2-C6F4PPh2)2] is unreactive. Computational studies have been performed to provide insights into the reasons for this difference in reactivity. Density Functional Theory (DFT) calculations show that formation of an AuCl adduct of [Pt(κ2-2-C6R4PPh2)2] is favoured over nucleophilic addition of PPh3 to Pt as the initial step of the reaction, and reveal the required energy of the cis and trans isomers of the bis-chelate [Pt(κ2-2-C6R4PPh2)2] in forming the mixed metal Pt–Au compounds. NBO analysis sheds more light on the bonding orbitals of the cis and trans isomers, suggesting that the Pt–P bonds in the cis isomer are more labile.

Chemical reactions modulated by mechanical stress: Extended Bell theory

A number of recent studies have shown that mechanical stress can significantly lower or raise the activation barrier of a chemical reaction. Within a common approximation due to Bell [Science 200, 618 (1978)], this barrier is linearly dependent on the applied force. A simple extension of Bell's theory that includes higher order corrections in the force predicts that the force-induced change in the activation energy will be given by -FΔR - ΔχF(2)∕2. Here, ΔR is the change of the distance between the atoms, at which the force F is applied, from the reactant to the transition state, and Δχ is the corresponding change in the mechanical compliance of the molecule. Application of this formula to the electrocyclic ring-opening of cis and trans 1,2-dimethylbenzocyclobutene shows that this extension of Bell's theory essentially recovers the force dependence of the barrier, while the original Bell formula exhibits significant errors. Because the extended Bell theory avoids explicit inclusion of the mechanical stress or strain in electronic structure calculations, it allows a computationally efficient characterization of the effect of mechanical forces on chemical processes. That is, the mechanical susceptibility of any reaction pathway is described in terms of two parameters, ΔR and Δχ, both readily computable at zero force.

Stereoselective synthesis of C-6 hydroxy tricyclic sulfone as a γ-secretase inhibitor

The synthesis of a C-6 hydroxy tricyclic sulfone was described with two key reactions: the Suzuki coupling and the regioselective and stereoselective cis ring opening of the epoxide. Overall, the 14-step synthesis was achieved in 2.1% yield.

Theoretical Study of the Acid-Promoted Hydrolysis of Oxazolin-5-one: A Microhydration Model

The acid-promoted hydrolysis of 2,4,4-trimethyloxazolin-5-one (TMO) is studied employing the density functional theory (B3LYP) method in conjunction with the 6-31++G(d,p) basis set. Two types of reaction mechanism, N-protonated and O-protonated, are considered, involving protonation at the nitrogen and carbonyl oxygen of TMO to activate the C2 and C5 atoms, respectively, in favor of attack by water molecules. In the N-protonated pathway, the nucleophilic water molecule attacks the activated C2 atom, with a proton transfer from the water molecule to the oxygen atom attached to C2 and the fission of the C2-O bond, leading to a cis ring-opening product (N-acyl-alpha-amino isobutyric acid). While, in the O-protonated pathway, the nucleophilic water molecule attacks the activated carbonyl C5 atom, accompanied by a proton transfer from the water molecule toward the nitrogen atom of oxazole ring and the cleavage of C5-O bond; as a result, a corresponding trans product is generated. The water-assisted hydrolysis reactions are also examined together. A local microhydration model, in which an extra water molecule was added to obtain a continuous H-bond network around the reaction centers, was adopted to mimic the system for the two types of reaction processes. In addition, bulk solvent effect is introduced by use of the conductor-like polarizable continuum model (CPCM). Our computational results in kinetics and thermodynamics clearly manifest that the O-protonated pathway with the nucleophilic attack at the carbonyl C5 atom is more favorable than the N-protonated one, in nice agreement with the available experimental conclusion.

Highly diastereoselective synthesis of nucleoside adducts from the carcinogenic benzo[a]pyrene diol epoxide and a computational analysis.

A diastereoselective synthesis of the nucleoside adducts corresponding to a cis ring-opening of the carcinogen (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaP DE-2) by 2'-deoxyadenosine and 2'-deoxyguanosine is described. The key intermediate (+/-)-10alpha-amino-7beta,8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene was synthesized by a highly diastereoselective dihydroxylation wherein phenylboronic acid was a water surrogate. The resulting boronate ester was converted to a tetraol derivative in which two of the four hydroxyl groups (trans 7, 8) were protected as benzoate esters while the remaining two (cis 9, 10) were free. The cis glycol entity was then subjected to a reaction with 1-chlorocarbonyl-1-methylethylacetate to yield an intermediate chloro monoacetoxy dibenzoate. Displacement of the halide with azide, complete cleavage of the esters, and catalytic reduction of the azide yielded the requisite amino triol. Fluoride displacement from appropriately protected nucleoside derivatives, 6-fluoropurine 2'-deoxyribonucleoside and 2-fluoro-2'-deoxyinosine, by the amino triol then yielded diastereomeric pairs of diol epoxide-adducted 2'-deoxyadenosine (dA) and 2'-deoxyguanosine (dG) nucleosides. Small aliquots of these adducts were separated for characterization purposes. The present approach provides the first diastereoselective synthesis of the cis adducts of BaP DE-2 with 2'-deoxyguanosine as well as the first synthesis of both dA and dG adducts from a common intermediate. An informative analysis of the 1H NMR spectra of the cis adducts synthesized and comparisons to the trans adducts are reported. To gain insight into the diastereoselectivity in the key dihydroxylation step, a computational analysis, including molecular mechanics (MMFF94) and semiempirical AM1 geometry optimizations, yielded results that are in fairly good agreement with the experimental observations.

Error-prone Translesion Synthesis by Human DNA Polymerase η on DNA-containing Deoxyadenosine Adducts of 7,8-Dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene

When human DNA polymerase eta (pol eta) encounters N6-deoxyadenosine adducts formed by trans epoxide ring opening of the 7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaP DE) isomer with (+)-7R,8S,9S,10R configuration ((+)-BaP DE-2), misincorporation of A or G and incorporation of the correct T are equally likely to occur. On the other hand, the enzyme exhibits a 3-fold preference for correct T incorporation opposite adducts formed by trans ring opening of the (-)-(7S,8R,9R,10S)-DE-2 enantiomer. Adducts at dA formed by cis ring opening of these two BaP DE-2 isomers exhibit a 2-3-fold preference for A over T incorporation, with G intermediate between the two. Extension one nucleotide beyond these adducts is generally weaker than incorporation across from them, but among mismatches the (adducted A*) x A mispair is the most favored for extension. Because mutations can only occur if mispairs are extended, this observation is consistent with the occurrence of A x T to T x A transversions as common mutations in animal cells treated with BaP DE-2 isomers. Adducts with S absolute configuration at the point of attachment of the hydrocarbon to the base inhibit incorporation and extension by pol eta to a lesser extent than their R counterparts. Template-primers containing each of the four isomeric dA adducts derived from BaP DE-2 and two adducts derived from 9,10-epoxy-7,8,9,10-tetrahydrobenzo-[a]pyrene in which the 7- and 8-hydroxyl groups of the DEs are replaced with hydrogens exhibit reduced electrophoretic mobilities relative to the unadducted oligonucleotides. This effect is largely independent of DNA sequence. Decreased mobility correlates with an increased rate of incorporation by pol eta, suggesting a systematic relationship between the overall DNA structure and efficiency of the enzyme.

Reductive ring opening of cis- and trans-2,3-diphenyloxirane: a common intermediate

The reaction of both cis- and trans-2,3-diphenyloxirane ( 7 and 4 , respectively) with an excess of lithium and a catalytic amount of 4,4′-di- tert-butylbiphenyl (DTBB, 2.5 mol%) in the presence of different carbonyl compounds as electrophiles (Barbier conditions) in THF at temperatures ranging between −80 and −50 °C gives the same organolithium intermediate 5 and consequently, the same 1,3-diols 6 . In the case of cis-epoxide an inversion of the configuration at the benzylic carbanionic center can explain the obtained results. Only for the dicyclopropyl ketone derivative ( 6h ) some amount (14%) of the corresponding epimer ( 6′ h ) resulting from a process with retention of the configuration of the intermediate is obtained. In representative cases, the structure of the final products ( 6 ) was unequivocally determined by X-ray diffraction analysis.

Control of aminophosphine chelate ring-opening in Pt(ii) and Pd(ii) complexes: potential dual-mode anticancer agents

We show that bis(aminophosphine) complexes of the type [M(R1R2N(CH2)nPPh2)2]2+, M = Pt(II) or Pd(II), can exist in chelate ring-closed and ring-opened forms both in the solid state and in aqueous solution. The equilibrium between them in solution can be controlled by the nature of the groups R1 and R2 (H, Me, Bz, cyclohexyl), by the bridge length n, and by the pH and Cl− concentration. X-Ray crystal structures are reported for the ring-closed complexes cis-[Pt(H2N(CH2)2PPh2-P,N)2]Cl2, cis-[Pt(H2N(CH2)3PPh2-P,N)2]Cl2, and cis-[Pt(Me(H)N(CH2)2PPh2-P,N)2][HCl2]2, the mono-ring-opened complex cis-[Pd(Me2N(CH2)2PPh2-N,P)Cl(Me2NH(CH2)2PPh2-P)](NO3)2, the di-ring-opened complex cis-[Pt(Me2N(CH2)3PPh2-P)2Cl2], and, for comparison, the monochelate cis-[Pd(Me2N(CH2)3PPh2-N,P)Cl2]. These square-planar complexes exhibit varying degrees of distortion and variable M–N bond lengths dependent not only on the trans influence of P but also on steric effects within the complex. pH-induced chelate ring-opening of cis-[Pt(Me2N(CH2)2PPh2-P,N)2]Cl2 had an associated pK value of 6.9. In contrast, complexes with R1 and R2 = H, n = 2 or 3 or R1 = H and R2 = Me, n = 2, are more difficult to ring-open. Thus the complexes cis-[Pt(Me(H)N(CH2)2PPh2-P,N)2]Cl2 and cis-[Pt(H2N(CH2)3PPh2-P,N)2]Cl2, had associated pK values of 2.1 and 2.9, respectively. These aminophosphine complexes may exhibit anticancer activity by two mechanisms: by disrupting mitochondrial membrane potentials as bis-chelated (ring-closed) lipophilic cations, or by direct binding to DNA bases as ring-opened complexes.

Synthesis of cis Adducts of Cyclopenta[cd]Pyrene with Deoxyguanosine and Deoxyadenosine

Recent analysis of DNA adducts of cyclopenta[cd]pyrene (CPP) formed in vitro by reaction of CPP-3, 4-oxide, with calf thymus DNA, suggested ring opening of the enantiomeric 3,4-epoxide predominantly by cis addition. We describe herein the chemical synthesis of DNA adducts resulting from benzylic cis ring opening of CPP-3,4-oxide by the exocyclic amino group of 2′-deoxyguanosine (dG) and 2′-deoxyadenosine (dA). The methodology involves synthesis of cis-3,4-dihydro-3-amino-4-hydroxycyclopenta[cd]pyrene followed by its coupling with appropriately protected halo-purinedeoxyribose intermediates. The diastereomeric mixture of products resulted in the coupling reaction was separated by HPLC and characterized by 1H NMR and MS analysis. Co-chromatography of the synthetic standards with in vitro adducts confirmed the identity and the stereochemical preference of the CPP-DNA adducts.

Diastereoselective ring opening of limonene oxide with water catalysed by β-ketophosphonate complexes of molybdenum(VI)

In the presence of catalytic quantities of [MoO 2Cl 2L] (L=β-ketophosphonate derived from camphor), water initiates the selective ring opening of cis (+) or (−)-limonene oxide to give the trans-diaxial diol. The trans isomer of the limonene oxide remains almost completely unreacted, thus providing a method for the kinetic separation of the trans diastereomer. 1H and 13C NMR studies of the interaction of the epoxide with the molybdenum complex show that the metal coordinates to the epoxide oxygen atom and that the diastereo-discriminating step is attack of MoO onto the tertiary carbocation formed by cleavage of a C–O bond in the epoxide.

Mutational consequences of replication of M13mp7L2 constructs containing cis-opened benzo[a]pyrene 7,8-diol 9, 10-epoxide-deoxyadenosine adducts.

The four adducts that arise by cis ring opening of the four optically active benzo[a]pyrene diol epoxides by the exocyclic N6-amino group of deoxyadenosine were incorporated synthetically into each of two different oligonucleotide 16-mers, 5'-TTTXGAGTCTGCTCCC-3' [context I(A)] and 5'-CAGXTTTAGAGTCTGC-3' [context II(A)], at the X position. The eight resultant oligonucleotides were separately ligated into bacteriophage M13mp7L2 and replicated in Escherichia coli that had been SOS-induced, and the progeny were analyzed to evaluate the consequences of replication past these adducts. The presence of these adducts reduced plaque yields substantially. However, the progeny obtained exhibited high frequencies of base substitution mutation ranging from 9 to 68%, depending upon the individual adduct and the sequence context in which it was placed. For most of the adducts, A --> T transversion was the mutation found most frequently in either sequence context, and mutation frequencies in context I(A) were always substantially greater than those in context II(A). In context I(A), adducts with an R configuration at the site of nucleoside attachment were more mutagenic than those with an S configuration. In both sequence contexts that were studied, the cis adduct arising from the (7S,8R)-diol (9S,10R)-epoxide was the most mutagenic adduct. These findings clearly show that individual mutation frequencies are determined by the combined effects of both adduct structure and sequence context.

La(otf)3-catalyzed 6-endo epoxide opening of 4, 5-epoxy-4-methoxymethyl-1-hexanols

The selective 6-endo epoxide ring opening of cis- and trans-4, 5-epoxy-4-melhoxymethyl-1-hexanols has been achieved by the chelation of La(OTf)3·nH2O between the oxygens of the epoxide and the methoxymethyl groups to afford 3-hydroxytetrahydropyran derivatives stereospecifically.

Synthesis and site-specific incorporation of a bay-region cis ring-opened tetrahydro epoxide-deoxyadenosine adduct into a DNA oligomer

Chemical synthesis of the 1,2,3,4-tetrahydrophenanthrene 3,4-epoxide adducts resulting from benzylic, cis ring-opening of the epoxide by the exocyclic amino group of 2'-deoxyadenosine (dA) is described. The approach taken consists of coupling (±)-cis-3-hydroxy-4-amino-1,2,3,4-tetrahydrophenanthrene with a 6-fluoro analogue of dA in which the furanose hydroxyl groups are protected. The required amino alcohol was obtained by reaction of 1,2-dihydrophenanthrene with osmium tetraoxide to form the cis 3,4-diol conversion to the trans chlorohydrin benzoate via its orthobenzoate, displacement of the benzylic chloride by azide, hydrolysis to the cis azido alcohol. Coupling of the amino alcohol with the 3',5'-bis-O-(tert-butyldimethylsilyl) derivative of 6-fluoro-9-(2-deoxy-β-D-erythro-pentofuranosyl)purine results in a pair of diastereomers that are readily separated by HPLC on silica gel

Cyclobutene photochemistry. Substituent and wavelength effects on the photochemical ring opening of monocyclic alkylcyclobutenes

The photochemical ring opening of cis- and trans-3,4-dimethyl-, 1,3,4-trimethyl-, and 1,2,3,4-tetramethylcyclobutene (1, 3, and 4, respectively) has been investigated in hydrocarbon solution with 193 nm and 214 nm light sources. Ring opening is non-stereospecific in all cases at both wavelengths. The ratio of dienes formed by the formally allowed to formally forbidden pathways in the photolysis of these compounds is highest (ca. 2) for the trimethylcyclobutenes, and approximately 1 for both cis and trans isomers of the di- and tetramethylcyclobutenes with 193 nm excitation. The diene distributions from photolysis of all compounds but cis-3 show slight wavelength dependence. Gas- and solution-phase UV absorption spectra are reported for 3 and 4, and indicate that there are at least three singlet excited states accessible in the 185–230 nm region in these molecules. The π,R(3s) state is the lowest energy state in the gas phase in 3 and 4. The results verify that orbital symmetry factors do not play a role (or a consistent one, at least) in controlling the stereochemistry of the reaction, but they do not allow a firm assignment of the excited state(s) responsible for ring opening. Direct photolysis of these compounds also results in fragmentation to yield Z-2-butene (from cis-3 and 4) or E-2-butene (from trans-3 and 4) in addition to propyne or 2-butyne. The 2-butenes are formed with greater than 90% stereospecificity in all cases. The structures of the four 3-methyl-2,4-hexadiene isomers obtained from photolysis of 3 have been assigned on the basis of 1H NMR spectroscopy and the results of thermolysis of the two cyclobutene isomers. Keywords: cyclobutene, photolysis, Rydberg, orbital symmetry, far-UV, solution phase, UV spectra.

ChemInform Abstract: Regioselective Ring Opening of cis‐ and trans‐Isophorole Epoxides (I), (III) and the Corresponding Acylated Isophoroles (VI) by Treatment with Trimethylamine Dihydrofluoride.

ChemInform Abstract: Regioselective Ring Opening of cis‐ and trans‐Isophorole Epoxides (I), (III) and the Corresponding Acylated Isophoroles (VI) by Treatment with Trimethylamine Dihydrofluoride.

Bioreductive alkylation as a trigger for toxic effects of dynemicin

The endiyne derivative, dynemicin, is postulated to undergo bioreductive cis ring opening of a benzylic epoxide and activate the endiyne unit for Bergman rearrangement to an arene-1,4-diyl.

Mechanism of ring opening of cis- and trans-1-methyl-2-aryl-3-aroylaziridine perchlorates under the influence of alcohols

The corresponding threo- and erythro-1,3-diaryl-3-alkoxy-2-N-methylamino-1-propanones, which are formed regio- and stereospecifically, were obtained by the reaction of cis- and trans-1-methyl-2-aryl-3-aroylaziridine perchlorates with alcohols.

ChemInform Abstract: THE MECHANISM OF THE BASE CATALYZED CARBONATO RING OPENING OF CIS‐(CO(CYCLEN)CO3)+

Chemischer InformationsdienstVolume 14, Issue 48 Organoelement Compounds ChemInform Abstract: THE MECHANISM OF THE BASE CATALYZED CARBONATO RING OPENING OF CIS-(CO(CYCLEN)CO3)+ R. W. HAY, R. W. HAYSearch for more papers by this authorA. K. BASAK, A. K. BASAKSearch for more papers by this author R. W. HAY, R. W. HAYSearch for more papers by this authorA. K. BASAK, A. K. BASAKSearch for more papers by this author First published: November 29, 1983 https://doi.org/10.1002/chin.198348276AboutPDF 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. Volume14, Issue48November 29, 1983 RelatedInformation

The Mechanism of the base catalysed carbonato ring opening of cis-[Co(cyclen)CO 3] +

The kinetics of carbonato ring opening of cis-[Co(cyclen)CO 3] + (cyclen = 1,4,7,10-tetraazacyclododecane) in basic solution has been studied in detail over a temperature range. The reaction shows a complex dependence on the hydroxide ion concentration with both first and second order terms in [OH −] occurring. The observed first order rate constant k obs is given by the equation ▪ Values of k 1K 1 and k 2K 1K 2 have been obtained and the apparent activation parameters determined. A mechanism is developed which can rationalise all the kinetic data.