Analysis Of Coupling Constants Research Articles

A 3 10-helix single turn enforced by crosslinking of lysines with 1,1′-ferrocenedicarboxylic acid

Prior work has shown that covalently linking the side chains of amino acids in the i and i+3 and i and i+4 positions in a peptide will enforce a helical conformation. In this work the ability of an organometallic entity to enforce a helical conformation in a peptide was explored. The tetrapeptide Boc-Lys-Ala-Val-Lys-NHCH 3 was prepared, then reacted with 1,1′-ferrocenedicarboxylic acid chloride. Reaction of the lysine side chain amines with the diacid chloride resulted in a metallacyclicpeptide ( 1) in which the two lysines are crosslinked via the ferrocene. The solution conformation of the metallacyclicpeptide ( 1) was studied using CD and NMR spectroscopy. The NMR methods employed were Karplus analysis of coupling constants, chemical shift changes of NH protons and ROESY data. The results show that the metallacyclicpeptide ( 1) adopts a single turn of the 3 10-helix conformation.

Diastereoselective, Three-Component Cascade Synthesis of Tetrahydrofurans and Tetrahydropyrans Employing the Tandem Mukaiyama Aldol−Lactonization Process

A full account of studies leading to the development of a cascade sequence that generates as many as two C-C bonds, one C-O bond, and three new stereocenters providing substituted tetrahydrofurans (THFs) from simple gamma-ketoaldehydes and thiopyridyl ketene acetals is described. The process involves a tandem Mukaiyama aldol-lactonization (TMAL) and accumulated evidence suggests the intermediacy of a silylated beta-lactone that is intercepted by the pendant ketone. Formation of a cyclic oxocarbenium is followed by reduction with silicon-based nucleophiles leading to a highly diastereoselective synthesis of tetrahydrofurans. This cascade process has now been extended to the synthesis of tetrahydropyrans from simple delta-ketoaldehydes. The stereochemical outcome of the cascade processes described was determined by NOE correlations, coupling constant analysis, and X-ray crystallography of the derived oxygen heterocycles and is in accord with established and recently proposed models for nucleophilic additions to cyclic 5- and 6-membered oxocarbenium ions. The utility of this process was demonstrated by the synthesis of the tetrahydrofuran fragment of colopsinol B.

A user-friendly Matlab program and GUI for the pseudorotation analysis of saturated five-membered ring systems based on scalar coupling constants

BackgroundThe advent of combinatorial chemistry has revived the interest in five-membered heterocyclic rings as scaffolds in pharmaceutical research. They are also the target of modifications in nucleic acid chemistry. Hence, the characterization of their conformational features is of considerable interest. This can be accomplished from the analysis of the 3JHH scalar coupling constants.ResultsA freely available program including an easy-to-use graphical user interface (GUI) has been developed for the calculation of five-membered ring conformations from scalar coupling constant data. A variety of operational modes and parameterizations can be selected by the user, and the coupling constants and electronegativity parameters can be defined interactively. Furthermore, the possibility of generating high-quality graphical output of the conformational space accessible to the molecule under study facilitates the interpretation of the results. These features are illustrated via the conformational analysis of two 4'-thio-2'-deoxynucleoside analogs. Results are discussed and compared with those obtained using the original PSEUROT program.ConclusionA user-friendly Matlab interface has been developed and tested. This should considerably improve the accessibility of this kind of calculations to the chemical community.

Contiguously Substituted Cyclooctane Polyols. Configurational Assignments via 1H NMR Correlations and Symmetry Considerations

More advanced oxidation of the cyclooctadienol shown, readily available in enantiomerically pure form from D-glucose, has given rise to a series of intermediates whose relative (and ultimately absolute) configuration was assigned on the basis of (1)H/(1)H coupling constant analysis. The selectivities that were deduced in this manner were drawn from the sequential application of CrO3 oxidation in tandem with Luche reduction, two-step NMO-promoted osmylations bracketed by acetonide formation, and wholesale deprotection. The stereoselectivities of these reactions were traced by (1)H NMR spectroscopy, and the stereochemical assignments were confirmed by the presence or absence of symmetry in the final cyclooctane polyols (four shown) generated in this investigation.

Conformational analysis of Hyptolide by DFT molecular modeling calculations and theoretical versus experimental NMR coupling constants analysis

Hyptolide belongs to a relevant group of cytotoxic compounds which occur in several members of the Lamiaceae family [1]. The conformational analysis of this highly flexible polyacylated-6-heptenyl-5,6-dihydro-2H-pyran-2-one was ascertained by a molecular modeling protocol which includes extensive systematic conformational searching [2], geometry optimization by DFT B3LYP/DGDZVP calculations, and comparison between the theoretical (DFT-GIAO) and experimental 1H-1H NMR couplings [3]. For the 28 more stable conformations, the root mean square difference between the observed and calculated couplings was smaller than 1Hz assuring the accuracy of the models.

13C-13C spin-spin coupling constants in structural studies: XLII. Stereochemical study on functionalized 2,5-dihydrofuran-2-imines

The configurations and conformations of twelve 5-imino-2,5-dihydrofuran-3-carboxamides and 5-imino-2,5-dihydrofuran-3-amines were determined by analysis of the experimental 13C-13C coupling constants and those calculated by nonempirical methods, as well as by quantum-chemical calculations of the total energies and optimization of geometric parameters of preferential conformations at the MP2/6-311G** level. All the examined compounds were found to be formed and to exist in solution as individual Z isomers with orthogonal orientation of the amino and dialkylamino groups and s-trans orientation of the carbamoyl group in the ring with restricted internal rotation about the C(O)-N bond.

Assignment of the Absolute Configuration of Goniodomin A by NMR Spectroscopy and Synthesis of Model Compounds

The complete absolute configuration of goniodomin A, an actin-targeting polyether macrolide isolated from the marine dinoflagellate Alexandrium hiranoi, was established from analysis of ROESY experiments and coupling constants, synthesis of suitable model compounds for NMR spectroscopic comparisons, degradation experiments, and correlation with synthetic reference compounds.

Stretched Poly(methyl methacrylate) Gel Aligns Small Organic Molecules in Chloroform. Stereochemical Analysis and Diastereotopic Proton NMR Assignment in Ludartin Using Residual Dipolar Couplings and 3J Coupling Constant Analysis

Poly(methyl methacrylate) (PMMA) gels prepared by copolymerizing methyl methacrylate (MMA) and various amounts of ethylene glycol dimethacrylate (EGDMA) in the presence of the radical initiator V-70 (2,2'-azobis(2,4-dimethyl-4-methoxyvaleronitrile)) can orient small organic molecules when swollen in NMR tubes with CDCl(3). The aligning properties of the stretched PMMA gels were evaluated by monitoring the quadrupolar splitting of the (2)H NMR signal of CDCl(3), and the aligning degree is proportional to the cross-linking density. Natural abundance one-bond (1)H-(13)C residual dipolar couplings (RDCs) for menthol measured in the gels depended on the cross-link density. The stereochemistry and assignment of the diastereotopic protons of the gastroprotective and nonsteroidal aromatase inhibitor sesquiterpene lactone ludartin, isolated from Stevia yaconensis var. subeglandulosa, were unambiguously determined using a combination of natural abundance one-bond (1)H-(13)C RDCs measured in a PMMA gel and a (3)J coupling constant analysis.

Structures of New Cytotoxic Antibiotics, Piericidins C7 and C8.

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Clarification of the C-35 Stereochemistries of Dinophysistoxin-1 and Dinophysistoxin-2 and Its Consequences for Binding to Protein Phosphatase

Okadaic acid analogues are well known as protein phosphatase inhibitors and occur naturally in marine shellfish feeding on dinoflagellates of the genus Dinophysis, leading to diarrhetic shellfish poisoning of shellfish consumers. Knowledge of the correct structures for these toxins is important in understanding their toxicology, biochemistry, and biosynthesis. We have performed extensive NMR analyses on okadaic acid (1), dinophysistoxin-1 (DTX-1), and dinophysistoxin-2 (DTX-2) obtained from natural sources. Consequently, we were able to unambiguously deduce the stereochemistries at C-35 for DTX-1 and DTX-2 based on analysis of NMR coupling constants and NOE interactions. Our results revealed that DTX-2 (3) has a stereochemistry opposite to that of DTX-1 (2) at C-35. Molecular modeling of the docking of 1-3 with protein phosphatase-1 and protein phosphatase 2A (PP2A) suggested that the reduced affinity of DTX-2 for PP2A may be due to the newly defined stereochemistry at the 35-methyl group. The implications of these findings for biosynthesis and toxicology are discussed.

A new eremophilanolide from Senecio sinuatus Gilib

From the hexane extracts of Senecio sinuatus roots, the new 3beta-angeloyloxy-6beta-hydroxyeremophil-1(10)-en-8beta,12-olide (3), along with the known compounds 3beta-angeloyloxy-6beta-hydroxyeremophil-1(10)-ene (1), 3beta-senecioyloxy-6beta-hydroxyeremophil-1(10)-ene (2), and 3beta-angeloyloxy-6beta,8alpha-dihydroxyeremophil-1(10)-en-8beta,12-olide (4), were isolated. Complete 1H and 13C NMR chemical shift assignments of 1-4 were achieved using one- and two-dimensional NMR techniques, including gHMQC and gHMBC experiments. A Monte Carlo search, followed by B3LYP/6-31G*DFT calculation, provided the theoretical conformations of the eremophilane rings, which were in agreement with results derived from 1H-1H NMR coupling constant analysis, and confirmed by NOESY experiments.

Structures of New Cytotoxic Antibiotics, Piericidins C7 and C8

Two new cytotoxic antibiotics, piericidins C7 (1) and C8 (2), were isolated from a marine Streptomyces sp. High-resolution FAB-MS established the molecular formulae of 1 and 2 as C28H41NO5 and C29H43NO5, respectively. The planar structures of the piericidins were elucidated by NMR spectral analysis including COSY, HMQC and HMBC. The relative stereochemistry of 2 was determined based on NOESY and coupling constant analyses. 1 and 2 are new members of the piericidin family possessing 11,12-epoxide and 12-butenyl groups.

Calculation of vibronic coupling constant and vibronic coupling density analysis

Vibronic coupling, electron–phonon interaction, constants of Jahn–Teller molecules, C 5H 5 and C 5D 5, are computed as matrix elements of the electronic operator of the vibronic coupling operator using the electronic wave functions calculated by generalized restricted Hartree–Fock (GRHF) and state-averaged complete active space self-consistent-field (CASSCF) methods. The calculated values of vibronic coupling constants for C 5H 5 and C 5D 5 agree well with the experimental values. Vibronic coupling density analysis can explain the isotope effect on the vibronic coupling from view of the electronic and vibrational structures. Changes of the vibrational modes as well as the frequencies upon the deuteration can affect the vibronic coupling. Vibronic density analysis provides a local picture of the coupling in a molecule, and it enables us to control the coupling. This could open a way to engineering of the vibronic coupling, vibronics.

An experimental and DFT analysis of coupling constants in [ 31P(CH 3) nH (4− n) ] + systems where n = 0–4 with a note on [ 14N(C 2H 5) 4] + and [ 31P(C 2H 5) 4] +

The experimentally determined coupling constants of phosphonium cations of general formula [P(CH 3) n H (4− n) ] + where n = 0–4 have been gathered and those corresponding to P ( CH 3 ) 4 + measured again. They have been compared with the coupling constants computed at the B3LYP/6-311++G(d,p)//B3LYP//6-311++G(d,p) level. The agreement is highly satisfactory save for 1 J PC and for 1 J PH. The last problem is probably related to specific solvation through hydrogen bonds. The cases of P ( C 2 H 5 ) 4 + and N ( C 2 H 5 ) 4 + were also examined to provide a basis for the fact that β protons show a large coupling constant with 14N than α protons.

Synthesis, stereochemistry and antimicrobial evaluation of t(3)-benzyl-r(2), c(6)-diarylpiperidin-4-one and its derivatives

In a wide research program toward new and efficient antimicrobial agents, a series of t(3)-benzyl-r(2), c(6)-diarylpiperidin-4-ones ( 1– 7) were synthesised and tested for their in vitro antibacterial and antifungal activities. Also, the structures and their stereochemistry of these synthesised compounds 1– 7 were characterized by IR, high resolution 1H NMR, 13C NMR and 1H– 13C COSY spectra. The analysis of coupling constants of compounds 1– 5 reveals that they exist in normal chair conformation with equatorial orientations of all the substituents. The spectra of 6 and 7 reveal the presence of two isomers labeled as E (carbonyl carbon is anti to benzyl group at C-3) and Z (carbonyl carbon is syn to benzyl group at C-3) in solution and the coupling constants ruled out the possibility of normal chair conformation. From the theoretical studies and coupling constant values the favoured conformation for the Z- and E-isomers of 6 and 7 was found to be the boat conformations. Their antibacterial activity against Streptococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae and antifungal activity against Cryptococcus neoformans, Candida 6, Candida 51, Aspergillus niger and Aspergillus flavus were also evaluated.

Unique {H(SiR3)2}, (H2SiR3), H(HSiR3), and (H2)SiR3Ligand Sets Supported by the {Fe(Cp)(L)} Platform (L=CO, PR3)

This work deals with the type and incidence of nonclassical Si--H and H--H interactions in a family of silylhydride complexes [Fe(Cp)(OC)(SiMe(n)Cl(3-n))H(X)] (X=SiMe(n)Cl(3-n), H, Me, n=0-3) and [Fe(Cp)(Me(3)P)(SiMe(n)Cl(3-n))(2)H] (n=0-3). DFT calculations complemented by atom-in-molecule analysis and calculations of NMR hydrogen-silicon coupling constants revealed a surprising diversity of nonclassical Si--H and H--H interligand interactions. The compounds [Fe(Cp)(L)(SiMe(n)Cl(3-n))(2)H] (L=CO, PMe(3); n=0-3) exhibit an unusual distortion from the ideal piano-stool geometry in that the silyl ligands are strongly shifted toward the hydride and there is a strong trend towards flattening of the {FeSi(2)H} fragment. Such a distortion leads to short Si--H contacts (range 2.030-2.075 A) and large Mayer bond orders. A novel feature of these extended Si--H interactions is that they are rather insensitive towards the substitution at the silicon atom and the orientation of the silyl ligand relatively the Fe--H bond. NMR spectroscopy and bonding features of the related complexes [Fe(Cp)(OC)(SiMe(n)Cl(3-n))H(Me)] (n=0-3) allow for their rationalization as usual eta(2)-Si--H silane sigma-complexes. The series of "dihydride" complexes [Fe(Cp)(OC)(SiMe(n)Cl(3-n))H(2)] (n=0-3) is different from the previous two families in that the type of interligand interactions strongly depends on the substitution on silicon. They can be classified either as usual dihydrogen complexes, for example, [Fe(Cp)(OC)(SiMe(2)Cl)(eta(2)-H(2))], or as compounds with nonclassical H--Si interactions, for example, [Fe(Cp)(OC)(H)(2)(SiMe(3))] (16). These nonclassical interligand interactions are characterized by increased negative J(H,Si) (e.g. -27.5 Hz) and increased J(H,H) (e.g. 67.7 Hz).

Conformational analysis of methyl 5- O-methyl septanosides: effect of glycosylation on conformer populations

Methyl 5- O-methyl-α- d- glycero- d-idoseptanoside ( 3) and methyl 5- O-methyl-β- d- glycero- d-guloseptanoside ( 4) were investigated as (1→5)-linked di-/oligoseptanoside mimetics. Here we report the synthesis of 3 and 4 and describe their preferred solution conformations through a combination of ab initio/DFT calculations and 1H 3 J H,H NMR coupling constant analysis. The conformations of 3 and 4 observed in this study are discussed in comparison to those of the parent (C5 hydroxy) compounds 1 and 2. The results indicate that methyl 5- O-methyl-α-septanoside 3 is relatively rigid and adopts the same 3,4TC 5,6 conformation as 1. Methyl 5- O-methyl-β-septanoside 4 is somewhat less rigid than its parent septanoside ( 2). In addition to the 6,OTC 4,5 conformation adopted by 2, β-septanoside 4 also populates the adjacent 3,4TC 5,6 conformation. Glycosylation at C5 on β-septanoside 4 therefore increases its overall flexibility and allows access to alternative ring conformations.

Structure and Dynamics of ASC2, a Pyrin Domain-only Protein That Regulates Inflammatory Signaling

Structure and Dynamics of ASC2, a Pyrin Domain-only Protein That Regulates Inflammatory Signaling

1H and 13C NMR spectra and solution structures of novel derivatives of 5-substituted creatinines

Five creatinine derivatives were prepared by the treatment of creatinine with activated carbon and appropriate alcohol ( 1–4), or ammonia solution ( 5). Product structures were determined by 1H and 13C NMR spectroscopy in solution, including 2D HSQC and HMBC experiments. Then, the proton and carbon chemical shifts for these compounds were calculated using GIAO–DFT [B3LYP/6-311G(2d,p)] method and the Gaussian 03W program and furthermore for 1 and 5 using polarizable continuum model (PCM). The conclusions coming from the comparison of the experimental and theoretical spectra supported the adopted signal assignments and solved the structural problems due to the potential annular tautomerism of the investigated compounds. One can predict that 5-substituted creatinines, just like creatinine, appear in solution in the form of 2-amino-1,5-dihydro-1-methyl-4-imidazolone. Correlations between experimental and calculated substituent-induced chemical shifts for two tautomeric forms of 5-substituted creatinines indicate that the mechanism of the substituent influence in both tautomers for the investigated compounds appears to be analogous. We can predict that in solution this accepting inductive effect of substituent groups does not significantly influence the structure of creatinine molecule in solution. The analysis of coupling constants for 5-substituted creatinines gives information about conformation of the investigated molecules in solution.

Calyculatine: a New Dolabellane Diterpenoid from the Marine Sponge Eunicea calyculata

A new dolabellane diterpenoid, 7(S)-hydroperoxy-13-keto-(1S,11R)-dolabella-3(E),8(17),12(18)-triene (1), and two known compounds, 7(S),8(S)epoxy-13-keto-1(S),11(R)-dolabella-3(E),12 (18)-diene (2) and 13-keto-1(S),11(R)-dolabella-3(E),7(E),12(18)-triene (3), were isolated from the marine sponge Eunicea calyculata. The structure of 1 was elucidated by 1D (1)H- and (13)C-NMR spectra and 2D HMQC, HMBC, and the relative stereochemistry was established by analysis of coupling constants and NOESY spectra. In addition, an X-ray crystallographic analysis on a single crystal of 2 was carried out. Compounds 1 and 2 were inactive in the hyphae formation inhibition assay (HFI) in Streptomyces 85E while compound 3 showed inhibitory activity at a concentration of 20 microg/20 microL in the HFI assay.