NOE Difference Spectra Research Articles

Synthesis and NMR conformational studies ofp-tert-butyldihomooxacalix[4]-arene derivatives

Abstract The tetramethyl (2) and tetraethyl (3) ethers, and the tetraacetate (4) derivatives of the p-tert-butyldihomooxacalix[4]arene were prepared. The mobility of these compounds studied by temperature-dependent 1H NMR spectroscopy. For the tetraacetate derivative, at room temperature, 1,2- or 1,3-alternate conformations are suggested. Those conformations were confirmed by NOE difference and COSY spectra for the tetraethyl ether derivative in CDCl3 at -20°C.

NMR determination of the structure of Julibroside J 1

Julibroside J 1 is a new triterpenoid saponin which contains one triterpene, two monoterpenes and nine sugar residues. The structure has been determined almost exclusively by high-resolution NMR methods. The 1H and 13C NMR spectra of Julibroside J 1 C 5D 5N have been assigned by homonuclear and heteronuclear correlation experiments, such as COSY, CH-COSY, TOCSY, HMBC, HMQC-COSY, HMQC-TOCSY and NOESY. Anomeric configurations were obtained by combined use of 1 J CH and 3 J H1,H2 and NOESY data. The particular sugar residues were identified by utilizing 3 J HH values obtained from TOCSY cross-peaks, NOE difference spectra, and several 1D-TOCSY spectra, and three-bond intra-ring cross-peaks from a HMBC spectrum. Linkage assignments were made using the HMBC spectrum, and supplemented by NOE data from the NOESY spectrum. The structure of Julibroside J 1 was characterized as 3-O-[β- d- xylopyranosyl-(1 → 2)-α- l- arabinopyranosyl-(1 → 6)-β- d- glucopyranosyl]-21-O-{(6S)-2- trans-2-hydroxymethyl-6- methyl-6-O-[4-O-((6S)-2-trans-2,6- dimethyl-6-O-(6- deoxy-β- d- glucopyranosy)-2,7- octadienoyl)-6- deoxy-β- d- glycopyranosyl]-2,7- octadienoyl}- acacic acid 28-O-{β- d- glucopyranosyl-(1 → 3)-[α- l- arabinofuranosyl-(1 → 4)]-α- l- rhamnopyranosyl-(1 → 2)}-β- d- glucopyranosyl ester.

Determination of the Stereochemistry of Four Spirodiastereoisomers by One- and Two-Dimensional NOE Studies

The stereochemistries of four cycloadducts obtained by 1,3-dipolar reactions were investigated with one-and two-dimensional NMR techniques. Analysis of a series of homonuclear NOE difference spectra and COSY and NOESY spectra recorded in a variety of solvents and at various temperatures allowed the determination of the full stereochemistry of each adduct.

1H NMR and Molecular Modeling Study on the Inclusion Complex β-Cyclodextrin−Indomethacin

The solution structure of the inclusion complex between β-cyclodextrin (2) and the nonsteroidal anti-inflammatory agent indomethacin sodium salt (1) [1-(p-chlorobenzoyl)-5-methoxy-2-methylindoleacetic acid sodium salt] is investigated in D2O solution via 1H NMR spectroscopy. The guest molecule 1 exists in solution as a mixture of E and Z isomers in fast exchange on the NMR time scale, as shown by NOE experiments. Low-temperature 1H NMR spectra on indomethacin methyl ester (3) (soluble in CH2Cl2-d2) showed that the Z isomer is the most thermodynamically stable. Geometrical features of the host−guest inclusion complex between 2 and 1 are inferred from intermolecular dipolar contacts obtained by 1D NOE difference spectra and 2D ROESY experiments. A more detailed picture of the solution structure of the complex is obtained by combining NMR structural information and molecular dynamics and energy calculations on the inclusion complexes. Computations took into account the existence of two diastereomeric forms of the guest (E and Z), the two possible sites of interaction of the guest molecule with the cavity (i.e. the p-chlorobenzoyl ring and the indole ring system), and the different topologies for the entry of the guest into the host's cavity. The main finding that can be obtained from both experimental and theoretical data is that the complexation selectively stabilizes the E isomer with respect to Z. The inclusion complex is characterized by the interaction of the p-chlorobenzoyl moiety of 1E with the lipophilic cavity of the host 2, the entry being through the larger rim of the truncated cone of 2.

Isolation and structure elucidation of tsugicolines A-D, novel protoilludane sesquiterpenes from Laurilia tsugicola1

Four novel Sesquiterpenes, tsugicolines A-D ( 1a, 2, 3a, 4), have been isolated from still cultures of the fungus Laurilia tsugicola (Basidiomycetae) Their structures were elucidated by means of chemical correlations and NMR studies and the relative configurations were established through a series of NOE difference spectra. The absolute configuration of tsugicoline A 1a (3- epi-illudol-5-one) was determined as 3S,6S,7R,9R,13S by the ‘partial resolution’ method of Horeau Treatment of tsugicoline A 1a with triethylamine in MeOH gave the metabolite 4; a possible mechanism is reported. Tsugicoline A is inactive on bacteria and fungi but inhibits the germination of the water cress Lepidium sativum.

NOE difference spectroscopy of some 5‐substituted and 5,5‐disubstituted hydantoins

AbstractThe nOe difference (NOED) spectra of twelve 5‐substituted‐ and 5,5‐disubstituted hydantoins were recorded in deuteriochloroform. The nOe's observed from the interaction of substituents on C‐5 with the proton on N‐1 are more reliable than the chemical shift of the N‐1 proton for structure determination.

Methine bases in the benzothiazole, benzoselenazole, and quinoline series, and geometry and conformational preferences of their acyl derivatives

Dimeric structures 2a–c are confirmed for the "methine bases" obtained from 2-methylbenzo-thiazolium and -selenazolium salts and aqueous sodium hydroxide, whereas monomeric structures 3 are confirmed for methine bases similarly derived from 2-methylquinolinium salts. The latter monomers dimerize slowly on standing. Monomeric methine bases 6–9, too hindered to dimerize, are described. 2-Acetonylidene-2,3-dihydro-3-methylbenzothiazole 10a and related compounds are assigned (Z) configurations on the basis of NOE difference spectra. Molecular mechanics calculations predict a slightly higher steric energy for the observed s-cis conformer of 10a than for the s-trans, indicating a stabilizing [Formula: see text] interaction in the s conformer that need only be a few kJ mol−1 in magnitude. For the quinolines 13a and b, the (E) configuration/s-cis conformation is favoured. The dielectric absorption method provides a rotational energy barrier of approximately 60 kJ mol−1 for acetyl group relaxation in 10a. Oxygen–sulfur exchange is observed in the conversion of 10a to 12a by thioacetic acid. Keywords: conformation, configuration, heterocyclic compounds, [Formula: see text] interaction.

The "Hidden" Exchange Partner in NMR Spectroscopy. Kinetic Properties and Implications in NOE Analysis

The presence of hidden exchange partners is a possible but not generally recognized source of negative effects in the 1H {1H} NOE difference spectra of molecules that fall in the extreme narrowing region. The true origin of these negative signals is not easily identified and this can lead to erroneous molecular structural conclusions. By introducing into the modified Bloch equations an extra term for transition probabilities induced by continuous selective RF irradiation, it is shown that in a two-site problem the "saturability" of the minor signal can be much lower than that of the major signal; this accentuates the possibility of spectral misinterpretations in NOE difference experiments. The occurrence of such a hidden partner in 1H spectroscopy is limited to a relatively narrow range of characteristic dynamical parameters (exchange rates, population ratios, relaxation times, and chemical-shift differences). Diagrams are provided for the assessment of population ratios using peak-height ratios determined from saturation-transfer difference experiments.

Eupomatenoids from Caryodaphnosis tonkinensis and their complete NMR assignment

AbstractEupomatenoids 3–6 and 13 were isolated from Caryodaphnosis tonkinensis and their 1H and 13C NMR spectra were assigned using 1D and 2D NMR techniques. Different assignment strategies are presented for the 1H and 13C chemical shifts. 1D NOE difference spectra, 1D APT, HMQC, HMBC, H,H‐COSY‐90 and delayed H,H‐COSY‐45 were used.

Preparation, structural analysis and anticonvulsant activity of 3- and 5-aminopyrazole N-benzoyl derivatives

Summary Some unsymmetrical N -exocyclic and N -endocyclic derivatives from benzoylation of 3- and 5-aminopyrazole were prepared with the aim of comparing their anticonvulsant activity towards the MES and scMET tests. Unambiguous proof of their structure was obtained from heteronuclear long-range correlation spectroscopy and NOE difference spectra. Only the N - exo -pyrazole benzamides showed good protection with respect to these tests.

Aromatic Nonpolar Nucleosides as Hydrophobic Isosteres of Pyrimidine and Purine Nucleosides.

Described are the design, synthesis, and structures of three nonpolar nucleoside isosteres to be used as probes of noncovalent bonding in DNA and as isosteric replacements for the natural nucleosides in designed nucleic acid structures. Reaction of substituted aryl Grignards with 3',5'-bis-O-toluoyl-α-deoxyibofuranosyl chloride and subsequent deprotection with sodium methoxide in methanol afforded the two β-C-nucleoside pyrimidine analogs 1 and 2. The dimethylindolyl nucleoside 3, a purine isostere, was obtained by a nucleophilic displacement on α-chlorodeoxyribofuranose by the sodium salt of 4,6-dimethylindole, followed by deprotection. Regio- and stereochemistry of the products were established with NOE difference spectra and (1)H NMR splitting patterns. Analogs 1 and 2 are nonpolar isosteres of thymidine, and nucleoside 3 is an isostere of 2-aminodeoxyadenosine, the triply-bonded Watson-Crick partner of thymidine. Semiempirical AM1 calculations were carried out to provide bond length information to assess structural similarities between the isosteres and their natural counterparts.

1H NMR analysis of some η 6-(substituted aryl phenylsulfonylacetonitrile)-η 5-cyclopentadienyliron cations

A detailed 1H NMR study of η 5-cyclopentadienyl-[η 6-(2,6-dimethylphenyl)phenylsulfonylacetonitrile]iron(II) and η 5-cyclopentadienyl-[η 6-( p-chlorophenyl) phenylsulfonylacetonitrile]iron(II) hexafluorophosphate salts ( Ia and IIa) using difference nOe spectra and 2-D (COSY) techniques has shown that there is an enhanced restricted rotation about the arene-methine carbon bond with the formation of the complexes Ia and IIa.

New Chalconoid Dimers fromMyracrodruon urundeuva

Abstract From the inner bark of a specimen of Myracrodruon urundeuva were isolated the new chalcone dimers 1 and 2, named urundeuvina A and B, as methyl ether derivatives (1a and 2a) obtained by methylation with diazomethane. The structure elucidation of these derivatives involved spectral data analysis, including 2D NMR experiments and NOE difference spectra.

Aldecalmycin, a new antimicrobial antibiotic from Streptomyces. II. Structure elucidation by NMR studies.

A new antibiotic, aldecalmycin (1) was isolated from the culture broth of Streptomyces sp. MJ147-72F6. The 1H and 13C NMR spectra of 1 were complicated due to the presence of a beta-ketoaldehyde moiety. Therefore, 1 was converted into an ethylene ketal derivative (2) and into a dihydroaldecalmycin (3). These derivatives gave assignable NMR spectra. The planar structure was elucidated by using 1H-1H COSY, 2D-HOHAHA, 1H-13C COSY and HMBC spectra of 2. The conformation of the decalin ring was elucidated by using ID-HOHAHA, NOE difference and NOESY spectra of 3. The geometry of double bond in the side chain was determined by NOE difference and NOESY spectra of 3.

Structures of New and Known Cyanoglucosides from a North American Plant, Purshia tridentata DC.

A new cyanoglucoside, purshianin (1), was isolated together with a known cyanoglucoside, menisdaurin (2a), from stems of Purshia tridentata DC. (Rosaceae) collected in Oregon, U.S.A. and the structure was established as (4S, 6S)-(Z)-6-(β-D-glucopyranosyloxy)-4-hydroxy-2-cyclohexene-Δ1, α-acetonitrile (1) based on chemical and spectral evidence. Notably, the absolute structure of 1 and the revised stereostructure (2), (4S, 6R)-(Z)-6-(β-D-glucopyranosyloxy)-4-hydroxy-2-cyclohexene-Δ1, α-acetonitrile for menisdaurin were decided based on combined studies of difference NOE spectra and Dreiding model inspection.

Bartanol and bartallol, novel macrodiolides from Cytospora sp. ATCC 20502

Two new macrodiolides, bartanol 10 and bartallol 11 have been isolated from a Cytospora sp. and their structures established by a detailed study of their high field 1H and 13C NMR spectra. Unlike the other 14-membered ring macrodiolides isolated from this source, bartanol and bartallol have a novel rearranged 13-membered macrocyclic ring. The conformations of the macrocyclic ring have been deduced from the analyses of difference NOE spectra and 1H–1H coupling constants.

Complete 1H (600 MHz) and 13C NMR spectral assignments of 3,4‐bis [(3,4‐dimethoxyphenyl)‐methyl]dihydro‐(3R‐trans)‐2(3H)‐furanone (matairesinol dimethyl ether), a naturally occurring dibenzylbutyrolactone lignan

AbstractThe concerted applications of a variety of one‐ and two‐dimensional NMR techniques (COSY, NOESY, HETCOR, COLOC, etc.) to the structural elucidation of the natural 3,4‐bis[(3,4‐dimethoxyphenyl)methyl]dihydro‐(3R‐trans)‐2(3H)‐furanone, isolated from Oenanthe aquatica fruits, in CDCl3 solution are reported. The magnitude of the 1H,1H coupling constants obtained from the simulated spectrum together with a series of homonuclear NOE difference spectra were used to determine the full stereochemistry of the system.

Structural reinvestigation of two diastereoisomeric aspidosperma–eburnea type bis‐indoles by NMR methods. Detection of a ‘hidden’ exchange partner and implications in noe analysis

AbstractFull 1H and 13C assignments are reported for two aspidosperma—eburnea type diastereoisomers. Homonuclear NOE difference measurements revealed that the previously reported configurational assignment of these compounds is in error. More interestingly, rotation about the bond connecting the two indole units is hindered in both molecules and gives a strongly biased two‐site chemical exchange system. At room temperature the exchange rates are slow on the chemical shift time‐scale with regard to certain 1H signals. In addition, the exchange rates are such that the signals due to the minor component are broadened to the extent that they escape detection in a conventional 1H spectrum, whereas only a very small amount of broadening is observed on the main signals. The presence of this ‘hidden’ exchange partner can give rise to peculiar effects in the NOE difference spectra. Such spurious effects can be the source of misinterpretation if the existence of the ‘silent partner’ goes unnoticed. Thermodynamic parameters are evaluated based on earlier work addressing the problem of the ‘hidden’ exchange partner.

1,2-Didemethylcolchicine: A New Alkaloid from Gloriosa superba

From the seeds of Gloriosa superba, the new alkaloid 1,2-didemethylcolchicine [2], was isolated, accompanied by known naturally occurring alkaloids colchicine, 2,3-didemethylcolchicine [1], 3-demethylcolchicine, N-formyl-N-deacetylcolchicine, and colchicoside. The structure of 1,2-didemethylcolchicine was secured by 1 H nmr with the help of decoupling and nOe difference spectra, ms, and [α]D

Evidence for the presence of the CH–π‐interacted ap‐conformers of benzyl formates

AbstractIn order to examine the preferred conformations of benzyl, 1‐phenylethyl and cumyl formates, lanthanoid‐induced shifts (LIS) of 1H and 13C NMR and difference NOE spectra of these esters were measured. The measurements showed that a folded conformer capable of forming intramolecular CH–π interaction are predominant with all three series of formate esters. The LIS and other experiments suggested the coexistence of considerable amounts of extended conformers, however. As the ester group is enforced to take supposedly unfavourable ap‐conformation in the CH–π contiguous folded conformer, the predominance of the conformer was a surprise and needed explanation. The NOE experiments on a series of para‐substituted benzyl formates, XC6H4CH2OCHO (X = CH3O, CH3, H, Cl, NO2), showed that the enhancement of aromatic proton signals (ortho and meta) induced by the irradiation of formyl proton increases gradually as the substituent becomes more electron donating, whereas the enhancement of benzylic (α) proton signal remains constant irrespective of the nature of the substituent. This can be explained by assuming that the CH–π contiguous folded conformer is in equilibrium with the extended conformer. The trend of the substituent effect supports the hydrogen bond‐like nature of the CH–π interaction. A similar trend was also observed with substituted 1‐phenylethyl formates. Hence the unexpected stability of the ap‐conformer of benzyl formates could be ascribed to the stabilization due to the CH–π interaction.