Structural Assignment of Stilbenethiols and Chalconethiols and Differentiation of Their Isomeric Derivatives by Means of 1H‐ and 13C‐NMR Spectroscopy

Abstract

The ¹H‐ and ¹³C‐NMR spectra of some substituted stilbenes and chalcones were assigned unambiguously on the basis of a combination of homo‐ (COSY) and heteronuclear (HETCOR) two‐dimensional methods, the chemical shifts, as well as spin‐coupling constants. The A_ik empirical parameters of the –O–C(S)–N(CH₃)₂, –S–C(O)–N(CH₃)₂, and –SH group were calculated to help predict the chemical shifts of substituted stilbenes, 4′‐nitrostilbenes, and chalcones. The ¹H‐ and ¹³C‐NMR spectra have been shown to be able to differentiate between the isomers of O‐stilbenyl (4, 5) and S‐stilbenyl N,N‐dimethylthiocarbamates (7, 8) as well as O‐chalconyl (6) and S‐chalconyl N,N‐dimethylthiocarbamates (9).     

Nuclear Magnetic Resonance Spectroscopy Study of a Disaccharidic Crown Ether.

Abstract

The disaccharidic anhydro derivative 6-O-(5,6-anhydro-3-deoxy-1,2-O-isopropylidene α-D-glucofuranos-3-yl)-1,2-O-isopropylidene-3-O-n-dodecyl-α-D-glucofuranose (1) led to the disaccharidic crown ether 2 in 40% yield when treated at low concentration with 2.5 eq. of KOH in toluene-Me₂SO. Compound 2 structure was proved through a detailed NMR analysis (¹H, ¹³C, ¹H-¹H and ¹³C-¹H 2D correlations). This structural elucidation indicated that compound 2 resulted from the intramolecular attack of the C-5-O^?alkoxide group, generated in the basic medium, on the C-6′ carbon of the 5′,6′-anhydro group.     

NMR Studies of Drugs. 1H and 13C NMR Chemical Shift Assignments in Etidocaine and Etidocaine Hydrochloride Determined by Two-Dimensional NMR Spectroscopy

¹H and ¹³C NMR chemical shift assignments were obtained for the local anesthetics etidocaine (1) and etidocaine hydrochloride (2) in CDCl₃ solution, as well as for 2 in D₂O solution. The COSY experiment was employed for proton-proton correlation, while onebond and long-range 2D heteronuclear techniques allowed the assignments of all ¹³C chemical shifts in each molecule. Etidocaine has a chiral carbon; etidocaine hydrochloride has, in addition to the natural chiral center, an acid-induced chirality at the protonated amine nitrogen, resulting in solvent-dependent diastereomers. Ten of the fourteen magnetically nonequivalent ¹³C nuclei of 2 exhibit doubled ¹³C resonance peaks (50.3 MHz, 20°C, CDCl₃ solution) due to the presence of the two diastereomers.     

NMR Studies of Crowded Diels–Alder Adducts of Phencyclone with N‐(2,6‐Dialkylphenyl)maleimides. Hindered Rotations and Magnetic Anisotropy

Abstract

Phencyclone, 1, reacted with N‐(2,6‐dimethylphenyl)maleimide, 2a; with N‐(2,6‐diethylphenyl)maleimide, 2b; and with N‐(2,6‐diisopropylphenyl)maleimide, 2c, respectively, to yield the corresponding Diels–Alder adducts, 3a–c. The adducts were extensively characterized by NMR (7 T) at ambient temperatures using one‐ and two‐dimensional (1D and 2D) proton and carbon‐13 techniques for assignments. Slow exchange limit (SEL) spectra were observed, demonstrating slow rotations on the NMR timescales, for the unsubstituted bridgehead phenyl groups [C(sp³)–C(aryl sp²) bond rotations] and for the 2,6‐dialkylphenyl groups [N(sp²)–C(aryl sp²) bond rotations]. Substantial magnetic anisotropic shifts were seen in the adducts. For example, in the N‐(2,6‐dialkylphenyl) moieties of the adducts, one of the alkyl groups is directed “into” the adduct cavity, toward the phenanthrenoid portion, and these “inner” alkyl proton NMR signals were shifted upfield. Thus, in CDCl₃, the “inner” methyl of adduct 3a exhibits a proton resonance at ?0.13 ppm, upfield of tetramethylsilane (TMS); the “inner” ethyl group signals from 3b appear at 0.026 ppm (CH₂, quartet), and ?0.21 ppm (CH₃, triplet); and the “inner” isopropyl group from 3c is seen at ?0.06 ppm (methine, approx. septet) and ?0.39 ppm (CH₃, doublet). Proton NMR of the crude N‐(2,6‐dialkylphenyl)maleamic acids (used as precursors of the maleimides, 2a–c) exhibited two sets of AB quartet signals, suggesting possible conformers from hindered rotation in the amide groups about the HN–C?O bonds.     

Toward direct determination of conformations of protein building units from multidimensional NMR experiments III

Chemical shielding anisotropy tensors have been determined, within the GIAO-RHF formalism using a smaller [6-31+G(d)] and two medium-size basis sets [6-311++G(d,p) and TZ2P], for all elements of the conformational library (altogether 27 structures) of the hydrophobic model peptide For-L-Phe-NH₂. The individual chemical shifts and their conformational averages have been compared to their experimental counterparts taken from the BioMagnetic Resonance Bank (BMRB). At the highest level of theory applied, for all nuclei but the amide proton, deviations between statistically averaged theoretical and experimental chemical shifts are as low as a few percent. One-dimensional (1D) chemical shift - structure plots do not allow unambiguous identification of backbone conformations. On the other hand, on chemical shift - chemical shift plots of selected nuclei, e.g., ¹H ^N with ¹⁵N or ¹⁵N with ¹³C ^α , regions corresponding to major conformational motifs have been found, providing basis for the identification of peptide conformers solely from NMR shift data. The 2D ¹H ^α -¹³C ^α as well as the 3D ¹H ^α -¹³C ^α -¹³C ^β chemical shift - chemical shift plots appear to be of special importance for direct determination of conformations of protein building units from multidimensional NMR experiments. 48 pairs of ¹H ^α -¹³C ^α data for phenylalanine residues have been extracted from 18 selected proteins and compared to relevant ab initio results, supporting the calculated results. Thus, the appealing idea of establishing backbone folding information of peptides and proteins from chemical shift information alone, obtained from selected multiple-pulse NMR experiments (e.g., 2D-HSQC, 2D-HMQC, and 3D-HNCA), has received further support.     

Stereochemical Elucidation of Norbornene Derivatives Synthesized as Leukotriene D4 Receptor Antagonists

The complete ¹H and ¹³C NMR assignment and stereochemical elucidation of four norbornene derivatives (1–4) are presented. These derivatives were obtained by an asymmetric Diels–Alder reaction of a chiral dienophile, from D‐glucose, as leukotriene D4 receptor antagonists. NOE measurements of the four products between H‐7b and H‐5 readily allowed discrimination between exo‐ (2, 4) and endo‐ (1, 3) diastereomers with respect to methyl carboxylate and tetrahydrofuro[1,3]dioxolyl groups. Further discrimination and subsequent absolute configuration determination of the two endo‐ and two exo‐ products were performed by NOE peak measurements and molecular modeling calculations of relative interproton distances of the most stable conformations of each isomer.     

13C NMR Chemical Shift of β-Alkoxyvinylketones: II. Empirical Substituent Effects in β-Aryl-β-Methoxyvinyltrihalomethylketones

Evaluation by empirically derived equations for the substituent effect (α,β,γ,δ) on the ¹³C NMR chemical shifts for C-1, C-2, C-3 and C-4 in β-aryl-β-methoxyvinylhalomethylketones 1a-g to 2a-g [R³C(O)-CH=C(Ar)-OMe, where R³ = CCl₃, CF₃ and Ar = p-YC₆H₄ (Y = H, Me, MeO, F, Cl, Br, NO₂)], taking as reference the β-ethoxyvinyltrichloromethylketone (3), is reported. From the calculated values for the α,β,γ,δ effects for each substituent it was possible to estimate the chemical shift of each carbon of the compounds 1,2. The ¹³C chemical shifts of the C-1, C-2, C-3, C-4 of these compounds, can be estimated with good to rasoable precision: 84% of the calculated chemical shifts are found to be within ±1.0ppm, and 100% are found to be within ±1.5ppm. The Y-Effects on C-3 and C-4 are compared with carbon charge densities (qr).     

1H and 13C NMR Spectral Study of Some 2r-Aryl-6c-phenylthian-4-ones,Their 1-Oxides and 1,1-Dioxides

ABSTRACT

Four 2r-aryl-6c-phenylthian-4-ones 1b?1e and their 1-oxides 2b?2e and 1,1-dioxides 3b?3e have been newly synthesized. ¹H and ¹³C NMR spectra have been recorded for all these compounds and 2r,6c-diphenylthian-4-one 1-oxide 2a. ¹³C NMR spectrum has been recorded for the sulfone 3a of 1a. For selected compounds ¹H-¹H COSY, HSQC, HMBC, and NOESY spectra have been recorded. The vicinal proton–proton coupling constants suggest that in all these compounds, the heterocyclic ring adopts chair conformation with equatorial orientations of the aryl and phenyl groups. Proton and carbon chemical shifts suggest that in the sulfoxides, the S=O bond is axial and enhances the J _aa value by some special effect. The S = O bond causes a significant upfield shift even on carbons without hydrogens. Significant solvent shifts also were observed.     

13C NMR Chemical Shifts of Heterocycles: 3∗. Empirical Substituent Effects in 2-Halomethyl-2-hydroxy-tetrahydrofurans and -5,6-tetrahydro-4H-pyrans

Abstract

Evaluation by empirically derived equations for the Substituent effect (α, β, γ, δ) on the ¹³C NMR chemical shifts for C-2, C-3, C-4, C-5, C-6, the halomethyl-substituted carbon (C-7) and the cyano or oxymic carbon (C-8) in 2-halomethyl-2-hydroxy-tetrahydrofurans 1a-c, 2, 3a, b, 4a and -5,6-tetrahydro-4H-pyrans 5a-c, 6a [with C-2-substituents (R²): CF₃, CCl₃ or CHCl₂, C-3-substituents (R³): CN, C(Me)=NOH, CH=NOMe, C(Me)=NOMe or CH=NOH], taking as reference the 2-trifluoromethyl-2-hydroxy-tetrahydrofuran (la), is reported. From the additivity properties of the α-, β-, γ-, δ-and ?-effects for each Substituent it is possible to predict the chemical shift of each carbon of the compounds 1–6.

     

13C NMR Chemical Shifts of β-Alkoxyvinyl Ketones: III✠-Empirical Substituent Effects in 1-Alkylamino-6-Ethoxy-1,5-Hexadien-3,4-Diones and 1,6-bis(Alkylamino)-1,5-Hexadien-3,4-diones

Evaluation by empirically derived equations for the substituent effect (E_Xn and E_Yn, n = 1 to 6) on the ¹³C NMR chemical shifts for C-1, C-2, C-3, C-4, C-5 and C-6 in 1-alkylamino-6-ethoxy-1,5-hexadien-3,4-diones 1a-f and 1,6-bis(alkylamino)-1,5-hexadien-3,4-diones 2a-f [XCH=CHC(O)-C(O)CH=CHY, where X, Y = OEt, NH₂, PhCH₂NH, n-BuNH, i-PrNH, cyclo-C₆H₁₁NH, t-BuNH], taking as reference the 1,6-diethoxy-1,5-hexadien-3,4-dione (3), is reported. From the calculated values for the E_Xn and E_Yn effects for each substituent it was possible to estimate the chemical shift of each carbon of the compounds 1,2 with excellent precision: 100% of the calculated chemical shifts are found to be within ±0.5ppm. The carbon-13 chemical shifts of C-1, C-2 and C-3 of compounds 1a,2a,3 led a good correlation with carbon charge densities (qr).     

Three-dimensional triple-resonance NMR Spectroscopy of isotopically enriched proteins. 1990

Four new and complementary three-dimensional triple-resonance experiments are described for obtaining complete backbone ¹H, ¹³C, and ¹⁵N resonance assignments of proteins uniformly enriched with ¹³C and ¹⁵N. The new methods all rely on ¹H detection and use multiple magnetization transfers through well-resolved one-bond J couplings. Therefore, the 3D experiments are sensitive and permit relatively rapid recording of 3D spectra (l–2 days) for protein concentrations on the order of 1 mM. One experiment (HNCO) correlates the amide ¹H and ¹⁵N shifts with the ¹³C shift of the carbonyl resonance of the preceding amino acid. A second experiment (HNCA) correlates the intraresidue amide ¹H and ¹⁵N shifts with the Cα chemical shift. This experiment often also provides a weak correlation between the amide NH and ¹⁵N resonances of one amino acid and the Ca resonance of the preceding amino acid. A third experiment (HCACO) correlates the Hα and Cα shifts with the intraresidue carbonyl shift. Finally, a 3D relay experiment, HCA(CO)N, correlates Ha and Cal resonances of one residue with the ¹⁵N frequency of the succeeding residue. The principles of these experiments are described in terms of the operator formalism. To optimize spectral resolution, special attention is paid to removal of undesired J splittings in the 3D spectra. Technical details regarding the implementation of these triple-resonance experiments on a commercial spectrometer are also provided. The experiments are demonstrated for the protein calmodulin (16.7 kDa).     

Infrared Spectra of the Square Planar Rhodium(I) Complexes cis-[Rh(CO)2(pyridine) (X)] (X = Cl,Br): Isotopic Labelling Studies and Normal Coordinate Analysis

Abstract

The infrared spectra (4000 - 50 cm^?1) of the square planar rhodium(I) complexes cis-[Rh(CO)₂ (pyridine) (X)] (X = Cl, Br) and their isotopomers with pyridine-d ₅ and ¹³CO have been determined. Assignments are based on earlier studies on pyridine and its complexes and on the shifts in infrared bands which are caused by the isotopic substitutions employed. Normal coordinate analysis following the procedure of Becher and Mattes has been used to confirm the empirical assignments. The two v(RhC) bands are observed near 490 and 450 cm^?1. v(RhN) is found near 210 cm^?1 and v(RhX) occurs at 310 (X = Cl) and 235 (X = Br) cm^?1. At frequencies below 200 cm^?1, the bands are assigned to bending modes in the following sequence: δ (RhN) > δ (CRhC) > δ (RhCl) > γ (RhCl) > γ (RhN).     

Design and Synthesis of Highly Photostable Yellow–Green Emitting 1,8-Naphthalimides as Fluorescent Sensors for Metal Cations and Protons

Two highly photostable yellow–green emitting 1,8-naphthalimides 5 and 6, containing both N-linked hindered amine moiety and a secondary or tertiary cation receptor, were synthesized for the first time. Novel compounds were configured as “fluorophore–spacer–receptor” systems based on photoinduced electron transfer. Photophysical characteristics of the dyes were investigated in DMF and water/DMF (4:1, v/v) solution. The ability of the new compounds to detect cations was evaluated by the changes in their fluorescence intensity in the presence of metal ions (Cu²⁺, Pb²⁺, Zn²⁺, Ni²⁺, Co²⁺) and protons. The presence of metal ions and protons was found to disallow a photoinduced electron transfer leading to an enhancement in the dye fluorescence intensity. Compound 5, containing secondary amine receptor, displayed a good sensor activity towards metal ions and protons. However the sensor activity of dye 6, containing a tertiary amine receptor and a shorter hydrocarbon spacer, was substantially higher. The results obtained indicate the potential of the novel compounds as highly photostable and efficient “off–on” pH switchers and fluorescent detectors for metal ions with pronounced selectivity towards Cu²⁺ ions.     

13C NMR Chemical Shifts of Heterocycles: Empirical Substituent Effects in 5-Halomethylisoxazoles

Evaluation by empirically derived equations for the Substituent effect (α, β, γ, δ) on the ¹³C NMR chemical shifts for C-3, C-4. C-5 and halomethyl-substituent carbon (C-6) in isoxazoles 1-5 [where C-3 substituent (R¹) = H, alkyl or phenyl, C-4 Substituent (R²) = H, alkyl, and C-5 substituent (R³) = di-or trihalomethyl, methyl and H], taking as reference the compound la, is reported. From the calculated values for the α, β, γ, δ effects for each substituent it was possible to estimate the chemical shift of each carbon of the compounds 1–5. The ¹³ C chemical shifts of the C-3, C-4, C-5, C-6 of these compounds, can be estimated with good precision: 94% of the calculated chemical shifts are found to be within ±1.0ppm, and 100% are found to be within ±1.5ppm.     

Conformational and Electronic Interaction Studies of P-Substituted α-Phenoxyacetones

The v_co analysis of p-substituted α-phenoxy-acetones X-θ-O-CH₂-C(O)-Me (1-6) indicates the existence of the cislgauche rotational isomerism. The nearly constant increase in the cislgauche population ratios for the whole series, on going from carbon tetrachloride to acetonitrile, and the small sensitivity of the carbonyl frequency shifts (Δv_c) for the cis rotamer, on going from electron-attracting to electron-donating substituents, are interpreted as an interplay of the Field (F) and the Inductive (-I) Effects, which originates an almost constant carbonyl bond order, and suggests that the cis rotamers have almost the same energy in the whole series. The decrease in the cislgauche population ratios, in all solvents, and the deshielding effects on the carbonyl carbon atom, and on the methylene carbon atom in a weaker extent, observed in the ¹³C NMR spectra, on going from electron-attracting to electron-donating substituents, are discussed in terms of φ*CO/ⁿO orbital and Ar^δ+ -O^δ- — C^δ+ =O^δ- Coulombic interactions, which stabilize the gauche rotamers of the investigated compounds.     

NMR Studies of Hindered Rotation and Magnetic Anisotropy: The Diels–Alder Adducts of Phencyclone with N‐Phenylmaleimide and N‐(2‐Trifluoromethylphenyl)maleimide. Ab Initio Calculations for Optimized Structures

Abstract

N‐Phenylmaleimide, 2, and N‐(2‐trifluoromethylphenyl)maleimide, 3, were separately added to phencyclone, 1, to yield the corresponding phencyclone Diels–Alder adducts, 4 and 5. The resulting adducts (and some precursors) have been characterized by one‐ and two‐dimensional ¹H and ¹³C NMR at 300 and 75 MHz, and by ¹⁹F NMR at 282 MHz, at ambient temperatures. The NMR data are consistent, for both adducts, with: (a) hindered rotation of the bridgehead unsubstituted phenyl groups about the C(sp²)–C(sp³) bonds, based on slow exchange limit (SEL) spectra and (b) endo adduct configuration based on magnetic anisotropic effects in the ¹H NMR. The NMR spectra of the phencyclone adduct, 4, of N‐phenylmaleimide, indicate free rotation on the NMR timescales (fast exchange limit, FEL spectra) about the N‐phenyl bond. The spectra for the adduct, 5, of N‐(2‐trifluoromethylphenyl)maleimide are interpreted as consistent with SEL regimes, for the N‐aryl rotations, with a single rotamer present in which the trifluoromethyl group is directed “out of” the adduct cavity, and away from the phenanthrenoid moiety. This conclusion is based, in part, on NMR data suggesting the apparent slow N‐aryl bond rotation in a pair of atropisomers corresponding to the acetic acid addition products from the N‐(2‐trifluoromethylphenyl)maleimide. Evidence of magnetic anisotropic effects due to the phenanthrenoid moiety and proximal carbonyls is discussed. ¹H, ¹³C, and ¹⁹F assignments are presented and interpreted. Molecular modeling calculations at the Hartree–Fock level, 6‐31G* basis set, were performed to provide geometry optimizations for energy‐minimized structures of selected compounds.     

滇黄精中两个呋甾皂苷的NMR研究

从滇黄精新鲜根茎中分离得到一对立体异构的呋甾皂苷, 利用1D、2D NMR鉴定其结构为: 26-O-β-D-吡喃葡萄糖基25(S)-呋甾-△^5（6）-烯-3β, 22, 26-三羟基-12酮基-3-O-β-D-吡喃葡萄糖基(1→4)-β-D-吡喃呋糖苷(1, 25S-kingianoside D)和26-O-β-D-吡喃葡萄糖基25(R)-呋甾-△^5（6）-烯-3β-, 22, 26-三羟基-12酮基-3-O-β-D-吡喃葡萄糖基(1→4)-β-D-吡喃呋糖苷(2, kingianoside D). 利用1D、2D NMR对两个呋甾皂苷25位的立体构型进行了确定, 并对其碳、氢信号进行了全归属.      

13C Nuclear Magnetic Resonance Studies of the Conformations of Serine‐3′‐ and 5′‐Thymidine Monophosphate Conjugates

The differences in the backbone conformation between O‐thymidine‐3′‐(1) and 5′‐yl O‐alkyl N‐phosphoryl serine methyl esters (2) have been investigated by solution ¹³C NMR spectroscopy. The stereo‐sensitive vicinal ³¹P–¹³C coupling constants were measured and used in the conformational analysis for the P–O5′–C5′, P–O3′–C3′, and P–N–C_α bonds. Three‐dimensional structural characteristics of dephosphorylation reactions of Compounds are also discussed.     

Hydroxyl Substituent Chemical Shift (SCS) Effects in Alcohols: The 17O NMR of Diols

The ¹⁷O NMR spectra for a series of saturated diols were investigated. From these studies both hydroxyl induced substituent chemical shift (SCS) effects of hydroxyl oxygen ¹⁷O NMR chemical shifts were determined. In addition, linear correlations between the ¹⁷O chemical shift of the hydroxyl oxygen (ROH) and the ¹³C chemical shift for the methyl group in the corresponding hydrocarbon (RCH₃) were obtained.

     

Vibrational Assignment of 2-Benzoyl Pyridine and its 18O Labelled Isomer

Abstract

Vibrational spectra of 2-benzoyl pyridine and 2-benzoyl pyridine-¹⁸O have been recorded in the solid and molten state in the infrared (4000–100 cm^?1) and in the Raman (4000–50 cm^?1). Polarized Raman spectra in the molten state have also been measured. The assignment of the vibrational bands is performed using the group vibrational concept, isotopic shifts and polarization features of the normal modes.