Model dipeptides incorporating the trans cyclohexane analogues of phenylalanine: further evidence of the relationship between side-chain orientation and β-turn type

In order to study the influence of the side-chain orientation on the peptide backbone conformation we have synthesised the model dipeptides t-BuCO-l-Pro-(1S,2R)-c₆Phe-NHMe and t-BuCO-l-Pro-(1R,2S)-c₆Phe-NHMe, incorporating each enantiomer of the trans cyclohexane analogue of phenylalanine (trans-1-amino-2-phenylcyclohexanecarboxylic acid). The orientation of the aromatic side-chain determines the β-turn type accommodated by these peptides to the point that the (1S,2R)-c₆Phe derivative retains the type I β-turn in the crystalline state, in contrast to the behaviour exhibited by the natural counterpart t-BuCO-l-Pro-l-Phe-NHMe.     

Aspartame analogues containing 1-amino-2-phenylcyclohexanecarboxylic acids (c6Phe). Part 2

This report describes the synthesis and conformational analysis of optically pure dipeptide analogues of aspartame, namely H-(S)-Asp-(1R,2S)-c₆Phe-OMe and H-(S)-Asp-(1S,2R)-c₆Phe-OMe, in which the Phe residue of aspartame has been replaced by a restricted Phe with a cyclohexane skeleton: 1-amino-2-phenylcyclohexanecarboxylic acid (c₆Phe). The dipeptide that incorporates (1R,2S)-c₆Phe is sweet whereas the compound that incorporates (1S,2R)-c₆Phe is bitter. This relationship between the absolute configuration of the dipeptides and the properties is explained in terms of the different conformational behaviour displayed by each molecule, as determined by molecular mechanics and molecular dynamics calculations that take into account solvent effects.     

Molecular species in liquid carboxylic acids

Measurements of dielectric permittivity and electric conductance are presented for mixtures of carboxylic acids — formic, trifluoroacetic, acetic and propionic — and non-polar liquids. For the dielectric and associative behavior of carboxylic acids a knowledge of the cis—trans conformational equilibria of the monomeric acid molecules seems to be essential. Therefore the cis and trans conformations of these molecules have been calculated by the CNDO/2 and PCILO methods. Appreciable rotational barriers for their interconversion have been obtained.     

The thermal isomerisation of some four co-ordinate square planar complexes of palladium and platinum with phosphine ligands

Thermally induced cis—trans isomerisation is reported for square planar complexes of the type MX₂L₂, M = Pd or Pt, L = organophosphorus ligand and X = halide. However, the palladium dichloro-phenyldimethyl complex provides another example of the more unusual trans—cis isomerisation. A number of phosphine complexes of platinum have been vacuum-distilled, in some cases with accompanying isomerisation. The tendency for such isomeric behaviour is interpreted in terms of variation in metal to phosphorus bond strength.     

Conformations and steric and stacking interactions of trisubstituted ureas and thioureas with alkyl and phenyl groups

The monomeric ν(N—H) vibrations of various trisubstituted ureas of the R₂UPh type and -thioureas of the R₂TUPh type have been studied. The trans—out isomerism in the former and the trans—out—cis isomerism in the latter are discussed from the point of view of steric effect. The monomeric ν(N—H) vibrations of RPhUPh and RPhTUPh are also examined. The single band appearing in the spectrum of both ureas is characteristic of the cis form; this suggests the existence of phenyl—phenyl interaction (the stacking interaction proposed by Galabov et al. [10]). Behavior of ν(N—H) vibrations at several concentrations is shown to be clearly different in the three forms (trans, out and cis). The presence of the cis form is confirmed by solvent effect experiments.     

Synthesis of 2-amino-1,3-diols incorporating the cyclobutane ring

The synthesis of free and protected 2-amino-1,3-diols with threoninol substructure that incorporate a conformational restriction defined by the cyclobutane ring is reported. The key step in the synthesis of these target compounds, namely cis- and trans-c₄-threoninols, is the addition of methylmagnesium bromide to a cyclobutanone derivative. The selectivity of the reaction is modulated by the solvent.     

Thermodynamic characteristics of phase conversion of structural isomers for volatile complex of ruthenium (III) trifluoroacetylacetonate

The comprehensive analysis of volatile β-diketonate compound—ruthenium(III) trifruoroacetylacetonate (Ru(tfac)₃)—was carried out. By means of flow method in quasi-equilibrium conditions and static method the temperature dependencies of saturated vapor pressure have been measured over solid and liquid cis- and trans-modifications of Ru(tfac)₃ and isomer mixture. The thermodynamic characteristics of sublimation, evaporation, melting, and phase conversion have been calculated for structural isomers. Also by differential-scanning calorimetry the temperature meanings and the thermodynamic characteristics of melting have been determined for individual isomers of Ru(tfac)₃ and their mixtures. By XRD the structures for cis- and trans-modifications have been determined. Both structures consist of neutral molecules arranged in pseudo layers.     

NMR study of cis3̄trans isomerism in N-methylated lactams with 11- and 13-membered rings

From ¹H-NMR spectra of 1-methyl-azacyclo-undeca-2-one and 1-methyl-azacyclo-trideca-2-one, the bands corresponding to the cis and trans forms have been assigned and analyzed; based on this analysis, conformational structures about the C-C bond next to nitrogen are proposed. By analysis of the relative areas and shapes of the N-methyl bands measured for the two lactams in 1,1,2,2-tetrachloroethane-d₂, over a broad temperature range, the equilibrium and thermodynamic parameters characterizing the cis—trans isomerism of the amide bond in these lactams have been determined. Peaks corresponding to the cis and trans forms in the ¹³C-NMR spectra of these lactams have also been assigned.     

Molecular conformations of methyl formate and methyl vinyl ether from ab initio molecular orbital calculations

Ab initio molecular orbital theory with minimal and extended basis sets and a flexible rotor geometric model has been used to investigate the rotational potential surfaces of methyl formate and methyl vinyl ether. For both molecules, the most stable structures (IA and IIA, respectively) are planar cis; additional potential minima are found which correspond to planar trans structures (IB and IIB). The latter lie respectively about 4—8 and 1—2 kcal mol^?1 above the corresponding cis rotational isomers. Methyl rotational barriers have been determined for cis and trans structures of each molecule. For trans methyl formate, there is a slight but unexpected preference for an eclipsed arrangement of the methyl group.     

Alkyl- und arylkomplexe des iridiums und rhodiums : VIII. Ungewöhnlich hoher trans-einfluss des carbonylliganden. Molekülstrukturen von cis- und trans-Ir(2,4,6-Me3C6H2)(CO)(PPh3)2

The molecular structures of cis- and trans-Ir(2,4,6-Me₃C₆H₂)(CO)(PPh₃)₂ have been determined by X-ray diffraction methods. Crystals of cis-Ir-(2,4,6-Me₃C₆H₂)(CO)(PPh₃)₂ (A) are monoclinic (P2₁/c) with a 1311.0(3), b 1888.5(6), c 1589.7(5) pm, β 101.85(2)°, and Z = 4. The trans complex B likewise crystallizes in the monoclinic space group P2₁/c with four molecules per unit cell, the lattice parameters being a 981.2(4), b 1214.7(7), c 3579.8(17) pm, and β 102.29(3)°. Based on 2971 and 2883 intensity data, the structures have been refined by full-matrix least squares to R values of 0.051 and 0.059 for A and B, respectively. The molecular geometries may be described as square planar. In the case of the cis-isomer the coordination shows some degree of tetrahedral distortion as a result of steric crowding. IrP distances in B are 231.3(5) and 231.9(5) pm, while in A IrP trans to mesityl is 232.4(3) pm, but trans to CO 237.0(3) pm. The carbonyl ligand thus seems to exert an even stronger trans-influence on IrP than the aryl group. This effect is discussed in terms of dπdπ participation in the metal—phosphine linkage. A very close contact of 244 pm is observed between the central metal and one of the ortho-methyl hydrogens in A which may contribute to kinetic stabilization of the thermodynamically unfavoured cis-isomer.     

Electronic spectra of α,β-unsaturated carbonyl compounds—II : An evaluation of increments characteristic of structural features of β-oxy-α,β-unsaturated ketones

By comparing UV spectra of β-alkoxy-α,β-unsaturated ketones of established steric structure, spectral constants characteristic of the cis/trans configuration change and s-cis/s-trans and O-s-cis/O-s-trans conformation changes have been evaluated. These are: Δλ^cis_trans = 0, Δλ^s-cis_s-trans = 8 nm and Δλ^O-s-trans_O-s-cis = 6 nm. A comparison of cis-s-cis enol ethers with the parent enols yielded the increment for the intramolecular (“chelating”) H-bond, Δγ_chel = 24 nm. The methanol-induced bathochromic shift has been found to depend strongly on s-cis/s-trans isomerism. The substituent increments have been shown to be dependent on the degree of substitution in the reference molecule. The results obtained have been summarized in a set of spectral increments complementing the basic system of Woodward and the Fiesers.     

Conformational analysis of N-methyl-m-fluoroaniline by microwave spectroscopy

Conformational analysis of N-methyl-m-fluoroaniline has been performed by low resolution microwave spectroscopy. Two rotational isomers, corresponding in a near-planar configuration to the m-fluorine being either cis or trans with respect to the amino hydrogen, have been detected. The energy difference is found to be 270 ± 70 cal mol^?1, the cis isomer being the more stable. Ab initio calculations indicate a barrier height for the internal rotation of the HNCH₃ group around the C_ph—N bond of 9.04 kcal mol^?1.     

Separation of 5-Lipoxygenase Metabolites Using Cyclodextrin-Modified Microemulsion Electrokinetic Chromatography and Head Column Field-Amplified Sample Stacking

A cyclodextrin-modified microemulsion electrokinetic chromatography method employing head column field-amplified sample stacking was developed for the analysis of arachidonic acid metabolites of the lipoxygenase pathways. The influence of the concentration of boric acid, the surfactant sodium dodecyl sulfate, the co-surfactant 1-butanol and the oil phase octane as well as the pH of the background electrolyte, the separation voltage and the separation temperature was studied. The optimized microemulsion consisting of 20 mM boric acid buffer, pH 9.0, 3.0 % (m/v) sodium dodecyl sulfate, 0.5 % (v/v) octane, 5.0 % (v/v) 1-butanol and 15 mM α-cyclodextrin enabled the separation of 20-hydroxy-leukotriene B₄, leukotriene B₄, 6-trans-leukotriene B₄, 6-trans-12-epi-leukotriene B₄, 5(S)-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid, 12(S)-hydroxy-5,8,14-cis-10-trans-eicosatetraenoic acid, 15(S)-hydroxy-5,8,11-cis-13-trans-eicosatetraenoic acid as well as the internal standard prostaglandin B₁ in <10 min employing a separation voltage of 17.5 kV at a temperature of 23 °C. A matrix peak from solid-phase extraction sample workup co-migrated with 5(S)-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid affecting peak integration. The addition of 5 % (v/v) 2-propanol to the microemulsion resulted in the separation of this eicosatetraenoic acid and the matrix components at the expense of analysis time and peak resolution between the diastereomers 6-trans-leukotriene B₄ and 6-trans-12-epi-leukotriene B₄. In summary, the MEEKC method appeared to be especially suitable for the more polar arachidonic acid metabolites.     

Conformational analysis,barriers to internal rotation,ab initio calculations and vibrational assignment of fluoroacetone

The infrared (3500-20 cm⁻¹) and Raman (3200-10 cm⁻¹) spectra have been recorded for gaseous and solid fluoroacetone (1-fluoro-2-propanone), CH₂FC(O)CH₃. Additionally, the Raman spectrum of the liquid has been recorded and qualitative depolarization values have been obtained. These data have been interpreted on the basis that the molecule exists predominantly in the cis (fluorine atom oriented cis to the methyl group) conformation in the vapor but for the liquid a second conformer having a trans orientation (fluorine atom oriented trans to the methyl group) is present. From a study of the Raman spectrum of the liquid at variable temperatures the trans conformation has been determined to be more stable than the cis form by 416 ± 54 cm⁻¹ (1.19 ± 0.15 kcal mol⁻¹) and is the only conformation present in the spectrum of the annealed solid. The asymmetric torsional fundamental for the more stable cis conformer has been observed in the far infrared spectrum of the gas at 69.6 cm⁻¹ with six accompanying hot band transitions proceeding to lower frequency. The corresponding mode for the high energy trans conformer is extensively overlapped but is distinguishable at ∼65 cm⁻¹. From these data the asymmetric torsional potential function governing internal rotation about the CC bond has been determined and the potential coefficients are: V₁ = 675 ± 2, V₂ = 991 ± 5, V₃ = 74 ± 1 and V₄ = 54 ± 2 cm⁻¹. The cis to trans and trans to cis barriers are 1332 ± 5 and 731 ± 5 cm⁻¹, respectively, with an enthalpy difference of 601 ± 8 cm⁻¹ (1.72 ± 0.02 kcal mol⁻¹). From ab initio calculations at the 3-21G and 6-31G* basis set levels optimized geometries for both the cis and trans conformers have been obtained and the potential surface governing internal rotation of the asymmetric top determined. The observed vibrational frequencies with their assignments for both the cis and trans conformers are compared to those from the ab initio calculations. All of these results are compared to the corresponding quantities for some similar molecules.     

Acid-catalyzed hydrolysis of alkyl vinyl and propenyl sulfides

The rates of acid-catalyzed hydrolysis of methyl, ethyl, isopropyl, and t-butyle vinyl sulfides have been measured in 10% aqueous acetonitrile. It was found that their reactivities decrease in this order. General acid catalysis was observed. The rate was smaller in a deuterium medium (k_D2O/k_H2O = 0.34). The deuterium exchange between sulfide and solvent was not detected during hydrolysis. Some propenyl sulfides have also been studied, their cis isomers being more reactive than the trans counterparts without geometrical isomerization involved. The reaction mechanism and the substituent effects on the reactivity have been discussed.     

The infrared spectra (500-150 CM−1) of the complexes cis- and trans-[Pt(pyridine)2X2] (X = Cl,Br, I,SCN)

The IR spectra of cis- and trans-[Pt(pyridine)₂X₂] (X = Cl, Br, I, SCN) are discussed. Distinction between the vPt—N and vPt—X bands is based on their relative sensitivities to ¹⁵N-labelling and deuteration of the pyridine ring, to halogen substitution and to ¹⁵NCS-labelling. Two vPt—N and two vPt—X bands are observed in the cis-complexes as required for C_2v symmetry. The D_2h symmetry of the trans-complexes requires one vPt-N and one vPt—X band but additional bands are observed and are ascribed to coupling between vPt—N and vPt—X.     

1,2- and 1,7-Dicarba-closo-dodecarborane(12)platinum(II) complexes formed through metal—carbon σ bonds: cis- and trans-monohydrido derivatives

New neutral platinum(II) monohydridocarborane complexes of general formula cis- and trans-L₂PtH(σ-carb), where L = (C₂H₅)₃P, (C₆H₅)₃P, (C₆H₅)₂(CH₃)P, (C₆H₅)(CH₃)₂P and carb = 2-R-1,2- or 7-R-1,7-B₁₀C₂H₁₀^? (R = H, CH₃, C₆H₅), have been prepared. The configurations of the complexes obtained have been assigned by ¹H NMR spectroscopy. The _cis-monohydridocarborane complexes here reported are the first examples of neutral _cis-monohydrido derivates of platinum(II) containing platinum—carbon σ bonds. ¹H NMR chemical shifts and coupling constants of the prepared complexes are also reported, and used in a tentative evaluation of the _trans-influence of the carbonage ligands.     

Infrared spectra and configuration of N,N'-diaryl-thioureas

The conformation of the —NH—CS—NH— grouping in a series of N,N'-diarylthioureas some of which possess a marked anti-viral activity is studied using IR spectral data. The results indicate that in organic solvents (CCl₄, CHCl₃, C₂C1₄, CH₂C1₂) the compounds studied participate in an equilibrium between several isomeric forms arising from the possibility of a cis or trans structure of the —CS—NH— groups. The increased solvent polarity favours the cis conformation.     

Structural studies of carbene complexes: The crystal structure of the secondary carbene complex RuI2[CHN(CH3)(p-CH3C6H4)](CO)(CN-p-CH3C6H4)(P(C6H5)3)

Crystal and molecular structures of the title compound have been determined from a three-dimensional X-ray analysis using diffractometer data. The crystals are triclinic, space group P$\text{1}$, with Z = 2 in a unit cell of dimensions a = 11.640(1), b = 10.9139(8), c = 16.587(2) Å, α = 87.983(5), β = 99.670(6), λ = 62.250(5)°. Full matrix least squares refinement has given a final R-factor of 0.043 for 2726 reflections for which I > 2σ(I).The crystal structure consists of discrete molecules of neutral complex together with water molecules which are hydrogen bonded into pairs [O ? O separation 2.60 Å]. 0The (H₂0)₂ units do not hydrogen bond to any other atoms. The ruthenium coordination is octahedral with trans carbene and isocyanide, cis iodides, and cis phosphine and carbonyl ligands. The Ru-donor distances are 2.776(2) [I trans to -PPh₃], 2.782(1) [I trans to -CO], 2.342(4) [PPh₃], 1.855(15) [CO], 2.046(15) [C(carbene)], and 1.998(16) Å [C(isocyanide)]. The bond lengths are discussed in terms of the trans effects of the ligands. The C(carbene)-N distance is 1.26(2) Å and the Ru—C(carbene)—N angle is 141.5(5)°.     

Stereoselective synthesis and Lewis acid mediated functionalization of novel 3-methylthio-β-lactams

A proficient etiquette for the stereoselective synthesis of novel 3-methylthio-β-lactams and their Lewis acid mediated functionalization is described. Treatment of 2-methylthioethanoic acid and appropriate imines in the Staudinger reaction leads to the stereocontrolled synthesis of novel trans-3-methylthio-β-lactams in excellent yields. cis-3-Chloro-3-methylthio-β-lactams, obtained from stereoselective chlorination of trans-3-methylthio-β-lactams using N-chlorosuccinimide (NCS) and AIBN, were subjected to Lewis acid (TiCl₄ or SnCl₄) mediated functionalization using various active aromatic, heterocyclic and aliphatic compounds (nucleophiles). This reaction provides an easy access to novel, stereoselective cis-3-monosubstituted-3-methylthio-β-lactams, which further undergo smooth desulfurization with Raney-nickel to afford C-3 cis- and trans-monosubstituted-β-lactams. The cis or trans configuration of the hydrogen/chloro/nucleophile substituent at C-3 was assigned with respect to C4–H.