Syn Configuration Research Articles

Retention of phosphorus configuration on forming irontetracarbonyl complexes with phosphines in the 9-phosphabicyclo[4.2.1]nonatriene and 7-phosphanorbornene systems

Dimers of phospholes with syn or anti configuration at the bridging phosphorus react with Fe 2(CO) 9 to give complexes, R 3PFe(CO) 4, with complete retention of configuration. Contrary to a report in the literature, isomers of 9-phenylbicyclo[4.2.1]nonatriene also formed complexes with complete retention of configuration.

Preparation of [(C5Me5)2Rh2B17H19]via a degradative insertion from anti-B18H22, and a possible mechanism for anti→syn macropolyhedral interconversion

Reaction of [(C5Me5)RhCl2]2 with anti-B18H22 in the presence of base yields, via boron vertex loss, a 19-vertex dirhodanonadecaborane [(C5Me5)2Rh2B17H19] of which the structure has been confirmed by X-ray crystallography; it comprises a 12-vertex nido{RhB11} subcluster and a 10-vertex nido{5-RhB9} subcluster conjoined with a common triangular {B3} face so as to generate an effective syn configuration.

Covalent carcinogenic lesions in DNA: NMR studies of O6-methylguanosine containing oligonucleotide duplexes

We report on proton and phosphorus high resolution NMR investigations of the self-complementary dodecanucleotide d(C1-G2-N3-G4-A5-A6-T7-T8-C9-O6meG10-C11-G12) duplexes (henceforth called O6 meG.N 12-mers), N = C, T, A and G, which contain N3.O6meG10 interactions in the interior of the helix. These sequences containing a single modified O6meG per strand were prepared by phosphoamidite synthesis and provide an excellent model for probing the structural basis for covalent carcinogenic lesions in DNA. Distance dependent nuclear Overhauser effect (NOE) measurements and line widths of imino protons demonstrate that the N3 and O6meG.10 bases stack into the duplex and are flanked by stable Watson-Crick base pairs at low temperature for all four O6meG.N 12-mer duplexes. The imino proton of T3 in the O6meG.T 12-mer and G3 in the O6meG.N 12-mer helix, which are associated with the modification site, resonate at unusually high field (8.5 to 9.0 ppm) compared to imino protons in Watson-Crick base pairs (12.5 to 14.5 ppm). The nonexchangeable base and sugar protons have been assigned from two dimensional correlated (COSY) and nuclear Overhauser effect (NOESY) measurements on the O6meG.N 12-mer helices. The directionality of the distance dependent NOEs establish all O6meG.N duplexes to be right-handed helices in solution. The glycosidic torsion angles are in the anti range at the N3.O6meG10 modification site except for O6meG10 in the O6meG.G 12-mer duplex which adopts a syn configuration. This results in altered NOEs between the G3 (anti).O6meG10 (syn) pair and flanking G2.C11 and G4.C9 base pairs in the O6meG.G 12-mer duplex. We observe pattern reversal for cross peaks in the COSY spectrum linking the sugar H1' protons with the H2',2" protons at the G2 and O6meG10 residues in the O6meG.N 12-mer duplexes with the effect least pronounced for the O6meG.T 12-mer helix. The proton chemical shift and NOE data have been analyzed to identify regions of conformational perturbations associated with N3.O6meG10 modification sites in the O6meG.N 12-mer duplexes. The proton decoupled phosphorus spectrum of O6meG.T 12-mer duplex exhibits an unperturbed phosphodiester backbone in contrast to the phosphorus spectra of the O6meG.C 12-mer, O6meG.G 12-mer and O6meG.A 12-mer duplexes which exhibit phosphorus resonances dispersed over 2 ppm characteristic of altered phosphodiester backbones at the modification site. Tentative proposals are put forward for N3.O6meG10 pairing models based on the available NMR data and serve as a guide for the design of future experiments.

Condensation products of formylcamphor with diamines : Structures in alcoholic solutions as derived from uv absorption and circular dichroism spectroscopy

The condensation products of optically active diamines with two molecules of formylcamphor have been investigated in methanolic solutions, where the formylcamphor chromophore is known to exist in the anti or (E) configuration. UV absorption and circular dichroism spectra are rationalised within an exciton formalism to give information about the absolute configuration. As with chloroform solutions, where the chromophore exists in the syn configuration, it is demonstrated that the title compounds may achieve the low energy conformation in seemingly different ways depending on substituents. Because of the different structure of the molecule when the chromophore is in the anti configuration as compared with the syn configuration, rotational conformations with respect to the substituted ethylene bridge in the same compound may be different in CH 3OH and CHCl 3. Finally “chelating solvation” in hydrogen bonding media is demonstrated through dissolution of the compounds in various alcohols.

Diastereofacial selectivity via aldol reactions using ethyl dithioacetate and ethyl dithiopropionate enolates

The lithium enolate of ethyl dithioacetate reacts with α-methyl aldehydes to yield the aldol products in which the syn configuration in the positions β and γ to the thiocarbonyl of the product is favored over the anti configuration. This selectivity is solvent-dependent, and is enhanced at lower temperatures. In most cases, syn:anti product ratios obtained under these conditions varied from 57:43 to >99:1, depending upon the structure of the α-methyl aldehyde. When the lithium enolate of ethyl dithiopropionate was allowed to react with α-methyl aldehydes, only two out of the four possible diastereomers were detected in the product mixtures.

Bimetallic systems. Part 11. Heterobimetallic and unsymmetrical diplatinum complexes from cis-[PtR2(dppm-P)2](dppm Å Ph2PCH2PPh2; R = Me, 1 -naphthyl, or C6H4Me-o): crystal structure of [(C6H4Me-o)2Pt(µ-dppm)2PtMe2

Treatment of cis-[Pt(C10H7)2(dppm-P)2](dppm = Ph2PCH2PPh2, C10H7= 1-naphthyl)(syn-anti mixture) with [Rh2Cl2(CO)4] gave [(C10H7)2Pt(µ-dppm)2RhCl(CO)] which showed a complex 31P-{1H} n.m.r. spectral behaviour with temperature. The analogue [(C6H4Me-o)2Pt(µ-dppm)2RhCl(CO)] was prepared in solution and behaved similarly. Treatment of cis-[Pt(C6H4Me-o)2(dppm-P)2] with [PtMe2(cod)](cod = cyclo-octa-1,5-diene) gave in solution a slowly equilibrating mixture of the syn- and anti-isomers of cis,cis-[(C6H4Me-o)2Pt(µ-dppm)2PtMe2], (4a) and (4b), respectively of which the minor (syn) isomer (4a) crystallized out and whose crystal structure has been determined. Treatment of [PtMe2(dppm-PP′)] with dppm at –30 °C gave cis-[PtMe2(dppm-P)2]in situ which on treatment with [{AgI(PPh3)}4], [AuCl(PPh3)], or AgPF6gave, respectively, [Me2Pt(µ-dppm)2AgI], [Me2Pt(µ-dppm)2Au]Cl, or [Me2Pt(µ-dppm)2Ag] PF6, all fully characterized. Solution 31P-{1H} n.m.r. studies showed that treatment of [PtMe2(dppm-P)2] with [MCl(Me)(cod)] gave the donor-acceptor cations [Me2Pt(µ-dppm)2MMe]+(M = Pt or Pd) in high yield. Crystals of the title compound are monoclinic, space group P21/n, with a= 12.371(2), b= 21.368(5), c= 21.917(5)A, β= 92.84(2)°, and Z= 4; the final R factor was 0.063 for 4 506 observed reflections. The structure confirms the cis square-planar co-ordination at both platinum atoms and shows the eight-membered Pt2P4C2ring in a twist saddle conformation with a Pt ⋯ Pt separation of 4.91 A. In the crystals used for data collection the o-tolyl groups adopt a syn configuration, which is shown to constitute the minor isomer in chloroform solution.

Des-, syn- and anti-oxyimino-delta 3-cephalosporins. Intrinsic reactivity and reaction with RTEM-2 serine beta-lactamase and D-alanyl-D-alanine-cleaving serine and Zn2+-containing peptidases.

The presence and configuration (syn or anti) of an oxyimino group in the 7 (beta)-acyl side chain of 3-cephems do not modify the intrinsic reactivity of the beta-lactam ring, but have highly enzyme-specific effects. When compared with the corresponding desoxyimino beta-lactam compound: (i) with the plasmid-mediated Escherichia coli RTEM-2 serine beta-lactamase, the substrate activity of the anti isomer is increased and that of the syn isomer is decreased; (ii) with the Streptomyces R61 serine D-alanyl-D-alanine cleaving peptidase (a highly penicillin-sensitive enzyme), the rate of enzyme acylation is not or only little affected when the oxyimino group is in the syn configuration, but is decreased when the oxyimino group is in the anti configuration; (iii) with the Actinomadura R39 serine D-alanyl-D-alanine-cleaving peptidase (an exceedingly highly penicillin-sensitive enzyme), the rate of enzyme acylation is unaffected whatever the configuration of the substituent. The oxidation of the sulphur atom of the dihydrothiazine ring on the beta-face of the molecule makes it both a poorer inactivator of the DD-peptidases and a poorer substrate of the beta-lactamase. The Streptomyces albus G Zn2+-containing D-alanyl-D-alanine-cleaving peptidase (a highly penicillin-resistant enzyme) remains highly resistant to all compounds tested.

Comparative mutagenesis by aminofluorene derivatives A possible effect of DNA configuration

The mutagenicity of N-acetoxy- N-2-acetylaminofluorene-( N-acetoxy-2AAF) for Salmonella typhimuricum TA98 is greatly reduced when compared to that of N-hydroxy-2-aminofluorene. This decrease in mutagenic response is accompanied by the formation of a deoxyguanosine-2-acetylaminofluorene adduct. The deoxyguanosine-2-aminofluorene adduct, characteristic of cells exposed to N-hydroxy-2-aminofluorene, was not detected in N-acetoxy-2AAF-treated cells. Enzymic deacetylation of N-acetoxy-2AAF results in restoration of potent mutagenicity. N-Acetoxy-2-acetylamino-7-iodofluorene is also more mutagenic than N-acetoxy-2AAF. Because the acetylated and unacetylated guanine induce greatly different configurational changes, the results may be indicative that the introduction of the syn configuration and a possible shift to the Z-conformation at the mutational hot spot of Salmonella typhimurium TA98 [(dG-dC) 8] results in reduced mutagenic potency.

Acidity measurements in THF. III. Aldimines and ketimines

The relative acidities of fiteen aldimines and ketimines have been measured in THF using either 13C nmr spectroscopy or trapping experiments with methyl iodide. The pKA's are found to vary over a range of more than four pK units. The effects of structure on acidity indicate the acid-weakening effect of alkyl substitution in ketimines to be due to steric effects. This interpretation is supported by the results of abinitio calculations. The data also permit a quantitative estimation of the preference for the syn configuration of lithiated imines to be at least four kcal/mol. The anti selectivity previously reported for the lithiation of endocyclic imines can be accounted for by angular constraints, as indicated by both abinitio calculations and pKa data on this class of imine.

13C lithiation shifts in aldimines and ketimines. Evidence on the configuration of lithiated N-tert-butylimines

The 13C shieldings for a series of aldimines and ketimines have been measured along with the shifts for their 1-lithio derivatives. For those aldimines with a primary or secondary alkyl group attached to nitrogen, the "lithiation shifts" for the attached carbon (C-4) were all upfield due to the change from anti to syn configuration on lithiation. In the ketimines and in the N-tert-butyl aldimines and ketimines, the lithiation shifts for the C-4 carbon failed to provide stereochemical information. The shifts at C-1 and C-2 proved similar to those previously observed for lithiated alkenes.

Complexes of methylmercury(II) with 1-methylcytosine and crystal structure of μ-(1-methylcytosinato-N3,N4)bis(methylmercury(II)) nitrate

Two types of solid complexes are isolated by reaction of CH3HgX (X = NO3 and ClO4) with 1-methylcytosine (MCy). The CH3Hg+ ion is probably bonded to N(3) in the [CH3Hg(MCy)]X compounds. Mercury binding to N(3) and the deprotonated amino group in [(CH3Hg)2(MCy—H)]X is confirmed by X-ray work on the nitrate salt. The crystals are orthorhombic, space group Pbca, with a = 12.014, b = 13.573, c = 16.353 Å, and Z = 8. The structure was refined on 962 independent reflections to an R factor of 0.038. The CH3Hg+ groups are arranged in a syn configuration and the angles around the mercury-bonded nitrogen atoms are severely distorted to prevent short Hg … Hg contacts. N(3)-coordination in the 1:1 complexes introduces minor changes in the infrared spectra, but the substitution of an amino proton in the 1:2 compounds produces important modifications. 1H nmr data in DMSO-d6 are reported for both types of compounds. This work emphasizes the important acidity enhancement experienced by the amino protons upon initial coordination to N(3), which facilitates further reaction of CH3Hg+ by proton displacement even in acidic media.

Tetronic acids and derivatives. Part XI . Structure of coupling products of tetronic acids with benzenediazonium sulfate

Abstract13C Nmr, 1H nmr and ir parameters of coupling products of tetronic acids (4‐hydroxy‐5H‐furan‐2‐ones) with benzene diazonium sulfate are only consistent with a phenylhydrazone formulation with an almost equal ratio of the syn and anti configurations. These results contrast with those of coupling products of acyclic 3‐ketoesters, existing mainly as anti tautomers, and more sharply with the 3‐parabromophenylhydrazone of L‐dehydro ascorbic acid, which is exclusively syn.

Pyrroloindoles. 4. Spatial isomerism of 3,8-diformyl-1H, 6H-pyrrolo[2,3-e]indole dioximes

It is shown that 3,8-diformyl-1H,6H-pyrrolo[2,3-e]indole dioxime is produced in the form of a mixture of geometrical isomers, which were separated by column chromatography. It was established by PMR spectroscopy that they have anti,syn and syn,syn configurations with a cisoid-transoid conformation of the side chains.

Carbon‐13 NMR characterization of the bispyridinium oximes, toxogonin, HS‐3, HS‐6 and HI‐6

AbstractThe structure of the bispyridinium oximes, toxogonin, HS‐3, HS‐6 and HI‐6, used as antidotes in organophosphorus poisoning, is confirmed by 13C NMR spectroscopy. The 13C NMR spectra of the corresponding monopyridinium precursors substantiate the signal assignment in the bispyridinium oxime spectra. In all oximes studied the hydroxyiminomethyl group (CHNOH) exists in the syn configuration. The 13C signal differences also readily allow analysis of binary mixtures of the oximes and provide an easy method for monitoring their stability.

Norbornadiene complexes of transition metals: III. Stereospecificity in the generation of cationic complexes [Rh(2,3,8 : 5,6-η-C 7H 7CHR)(η-C 5H 5)] + (R = Me, Ph, [Rh(2,3,8 : 5,6-η-C 7H 7CH 2)(η-C 5H 5)] +PF 6t-

Treatment of (2-hydroxymethylnorbornadiene)cyclopentadienylrhodium (V) with sulfuric acid offers the stable cationic complex XI, which can be isolated as PF 6 − or BF 4 −. 1H and 13C NMR data indicate that in cation XI the bicyclic ligand is bound to the metal via η 2-ethylene and η 3-allyl bonds, including an exocyclic methylene carbon. The structure of complex XI is supported by a single-crystal X-ray diffraction study of its PF 6 − salt. Reaction of diastereomeric carbinols ψ- exo-VI and ψ- endo-Rh {η 4-C 7H 7CH(OH)Me} (η 4-C 5H 5) (VII) proceeds with absolute stereospecificity to form syn-XII and anti-[Rh(η 5-C 7H 7CHMe)(η 5a-C 5H 5)] + (XIII) isomers, respectively. Similarly, cation [Rh(η 5-C 7H 7CHPh)(η 5-C 5H 5)] + (XV), derived from ψ- endo-Rh {η 4-C 7H 7CH(OH)Ph}(η 5-C 5H 5) (IX), has the syn configuration. However, the same reaction of the ferrocenyl-substituted carbinol ψ- endo-Rh {η 4-C 7H 7CH(OH)Fc} (η 5-C 5H 5) (X) leads to mixture of two isomeric complexes, syn-(XVI) and anti-[Rh(η 5-C 7H 7CHFc)(η 5-C 5H 5)] + (XVII), in a ratio of 4 1 . The absolute stereospecificity and the relative facility with which the formation of cationic η 3-allylic complexes from carbinols VI, VII and IX takes place are due to the nucleophilic participation of a rhodium atom in stabilizing the electron-deficient center during the reaction. The disturbance of stereospecificity during the conversion of carbinol X to a cationic complex assumes the formation of an α-ferrocenylcarbenium ion (XIX) as an intermediate (a product of kinetic control). Owing to the relative non-hindrance of rotation around the exocyclic carboncarbon bond C(2)—C(8) in the carbenium ion XIX, the formation of a non-equal mixture of complexes XVI and XVII, the products of thermodynamic control of the reaction, takes place.

Configuration and conformation of lithiated imines by DNMR studies and ab initio calculations

The N-isopropyl imine of lithioacetaldehyde, I, was found to exist as a 50 : 50 mixture of two isomers, as seen below 20°C by 1H and 13C NMR. Comparison of the population ratio and spectral characteristics of the isomers of this and related lithiated imines leads to the conclusion that they are rotamers all of which possess the syn configuration. This conclusion is supported by calculations of the barriers to interconversion.

Transition-metal–diene complexes. Part 3. Isomerization of methyl-substituted acyclic and cyclic 1,3- and 1,4-dienes co-ordinated to rhodium(I)

A range of methyl-substituted acyclic and cyclic 1,4-dienes co-ordinated ton RhI in the complexes [Rh(cp)(diene)](cp = cyclopentadienyl) undergo virtual quantitative isomerization when heated in non-protic solvents. Reactants and products have been characterized by chemical and physical methods, particularly by 1H n.m.r. spectroscopy. Reaction products are exclusively conjugated dienes and with one exception, cis,cis-hexa-2,4-diene, are co-ordinated to RhI. For the case of the acyclic 1,4-dienes the primary isomerizations, generally to mixtures of cis- and trans-1,3-isomers, are followed by a slower isomerization of the cis-primary product dienes to the trans isomers. For the isomerization of the cyclohexa-1,4-dienes, mixtures of 1,3-isomers are generally obtained in a primary process only. First-order rate constants for the decay of reactant 1,4-diene are reported. From an analysis of the kinetics of the reactions and of product distributions, a mechanism involving a (η3-allyl) hydrido-intermediate is proposed for the primary isomerizations in which the first step is the dissociation of one double bond from the metal. For the secondary isomerization of cis- to trans- 1,3-dienes a η3–η1–η3 interconversion of anti and syn configurations is suggested as the key step. The primary reactions are shown to be under kinetic control. However, addition of an external proton source leads to rapid formation of the thermodynamically most stable products via a metal hydride addition–elimination mechanism.

ChemInform Abstract: DOUBLE‐STRANDED DNA STEREOSELECTIVELY BINDS BENZO(A)PYRENE DIOL EPOXIDES

BEFORE it can exert its mutagenic and carcinogenic activities1,2 benzo(a)pyrene (BP) requires metabolic activation and it is widely considered3–5 that the initiating event in these processes is covalent binding to DNA. The predominant form of the activated hydrocarbon is a diol epoxide6–11, of which four possible isomers are (+) and (−) enantiomers of 7β,8α-dihydroxy-9α-10α-epoxy-7,8,9,10-tetrahydro-BP (anti-BP diol epoxide) and (+) and (−) enantiomers of 7β,8α-dihydroxy-9β,10β-epoxy-7,8,9,10-tetrahydro-BP (syn-BP diol epoxide). Enzymatic formation of the (+) anti and (+) syn configurations have been reported elsewhere12,13. We have shown that the racemic (±) anti-BP diol epoxide forms two stable covalent adducts each with the exocyclic amino groups of deoxyguanosine, deoxyadenosine and probably deoxycytidine14. We report here that we have now resolved the enantiomers of (±) anti-BP diol epoxide and reacted the optically pure hydrocarbons with DNA. Each enantiomer reacts with the exocyclic amino group of deoxyguanosine to form a pair of diasteriomers in a ratio which depends on the secondary structure of the nucleic acid. The (+) enantiomer reacts preferentially or asymmetrically with deoxyguanosine in double stranded DNA but the two enantiomers react equally with the same position in single-stranded DNA. The basis for the stereoselective binding is unknown but may involve formation of sterically orientated physical complexes before covalent attachment of the hydrocarbon to DNA. The mode of binding in the deoxyadenosine sites, on the other hand, must be different, as the (+) and (−) enantiomers react equally in either single- or double-stranded DNA.

Double-stranded DNA steroselectively binds benzo(a)pyrene diol epoxides.

BEFORE it can exert its mutagenic and carcinogenic activities1,2 benzo(a)pyrene (BP) requires metabolic activation and it is widely considered3–5 that the initiating event in these processes is covalent binding to DNA. The predominant form of the activated hydrocarbon is a diol epoxide6–11, of which four possible isomers are (+) and (−) enantiomers of 7β,8α-dihydroxy-9α-10α-epoxy-7,8,9,10-tetrahydro-BP (anti-BP diol epoxide) and (+) and (−) enantiomers of 7β,8α-dihydroxy-9β,10β-epoxy-7,8,9,10-tetrahydro-BP (syn-BP diol epoxide). Enzymatic formation of the (+) anti and (+) syn configurations have been reported elsewhere12,13. We have shown that the racemic (±) anti-BP diol epoxide forms two stable covalent adducts each with the exocyclic amino groups of deoxyguanosine, deoxyadenosine and probably deoxycytidine14. We report here that we have now resolved the enantiomers of (±) anti-BP diol epoxide and reacted the optically pure hydrocarbons with DNA. Each enantiomer reacts with the exocyclic amino group of deoxyguanosine to form a pair of diasteriomers in a ratio which depends on the secondary structure of the nucleic acid. The (+) enantiomer reacts preferentially or asymmetrically with deoxyguanosine in double stranded DNA but the two enantiomers react equally with the same position in single-stranded DNA. The basis for the stereoselective binding is unknown but may involve formation of sterically orientated physical complexes before covalent attachment of the hydrocarbon to DNA. The mode of binding in the deoxyadenosine sites, on the other hand, must be different, as the (+) and (−) enantiomers react equally in either single- or double-stranded DNA.

Coordination compounds of hydrazine derivatives with transition metals—XV Electronic and 1H NMR spectra of some diamagnetic metal(II) chelates with bidentate Schiff bases derived from hydrazine-S-methyl-dithiocarboxylate and thiosemicarbazide

A series of diamagnetic bis ligand Zn(II), Cd(II), Hg(II), Ni(II) and Pd(II) chelates with some Schiff bases derived from hydrazine-S-methyldithiocarboxylate(III) and the corresponding acid amide(IV) were prepared and characterized. The H NMR spectral studies showed that the Schiff base ligands derived from aromatic aldehydes as well as their metal(II) chelates exist only in one configuration with the aldehydic hydrogen syn to the NN bond. The ligand (III) derived from asymmetric ketones exist as a mixture of syn and anti configurations. The H NMR spectra of the corresponding Zn(II), Cd(II), Hg(II) and Ni(II) chelates indicate the presence of a trans isomer in syn and anti configurations. The spectra of Pd(II) chelates with ligand (III) show the possible existence of both cis and trans isomers in both syn and anti configurations. Besides, the syn and anti configurations, the Zn(II) and Ni(II) chelates with (III, R 1 = CH 3, R 2 = CH 2C 6H 5) appear to exist in different conformations. Ni(II) chelates derived from acetophenone derivatives exist predominantly in cis-syn configuration.