Selective INEPT Experiments Research Articles

ChemInform Abstract: Chromones and Flavanones from Artemisia campestris subsp. maritima.

Abstract From the acetone extract of Artemisia campestris subsp. maritima six flavanones, two chromones and the coumarin scopoletin were isolated. 5-Hydroxy-7-methoxychromone and 5,7-dimethoxychromone are new compounds, while the flavanone eriodictyol-7,3′-dimethyl ether is reported for the first time in this species. The structures were elucidated by 1D and 2D NMR techniques. The unequivocal assignments of carbon resonances, mainly made by using 1D selective INEPT and 2D HETCOR experiments, allowed us to correct some 1H and 13C resonances of the isolated flavanones and also to differentiate between the flavanone isomers sakuranetin⧹isosakuranetin and eriodictyol-7,3′-dimethyl ether⧹eriodictyol-7,4′-dimethyl ether.

Synthesis and NMR characteristics of N‐acetyl‐4‐nitro, N‐acetyl‐5‐nitro, N‐acetyl‐6‐nitro and N‐acetyl‐7‐nitrotryptophan methyl esters

N-acetyl-4-nitrotryptophan methyl ester (2), N-acetyl-5-nitrotryptophan methyl ester (3), N-acetyl-6-nitrotryptophan methyl ester (4) and N-acetyl-7-nitrotryptophan methyl ester (5) were synthesized through a modified malonic ester reaction of the appropriate nitrogramine analogs followed by methylation with BF(3)-methanol. Assignments of the (1)H and (13)C NMR chemical shifts were made using a combination of (1)H-(1)H COSY, (1)H-(13)C HETCOR and (1)H-(13)C selective INEPT experiments.

Methylation of Acridin-9-ylthioureas. Structure, Fluorescence and Biological Properties of Products

The structure, fluorescence, biological properties and S(N)-methylation reactions of ten 1,1-alkyl/aryl-disubstituted 3-(acridin-9-yl)thioureas 4 have been studied. Various reaction conditions allowed to obtain corresponding S-methyl 5 and S,N-dimethyl derivatives 6 in good yields. Structure and stereochemistry of the synthesized products are demonstrated by ab initio quantum chemical calculations and NMR techniques including PDQF-COSY, selective INEPT and NOE-difference experiments. Remarkable upfield 13C shifts of resonance signals of carbons C-4a, C-10a adjacent to acridine N-10 are characteristic of hydroiodides in contrast to free bases. Z configuration in isothioureas 7 with secondary amino rest in relation to E configuration of isothioureas with primary amino rest is discussed. Of the obtained products, some isothiourea salts 6 exhibit more than 2 orders of magnitude higher intensity of fluorescence, using 9-isothiocyanatoacridine as a standard. The obtained isothiourea hydroiodides 5 and dimethylisothiourea iodides 6 show remarkable biological activity against Mycobacterium tuberculosis.

Chromones and flavanones from artemisia campestris subsp. maritima

From the acetone extract of Artemisia campestris subsp. maritima six flavanones, two chromones and the coumarin scopoletin were isolated. 5-Hydroxy-7-methoxychromone and 5,7-dimethoxychromone are new compounds, while the flavanone eriodictyol-7,3′-dimethyl ether is reported for the first time in this species. The structures were elucidated by 1D and 2D NMR techniques. The unequivocal assignments of carbon resonances, mainly made by using 1D selective INEPT and 2D HETCOR experiments, allowed us to correct some 1H and 13C resonances of the isolated flavanones and also to differentiate between the flavanone isomers sakuranetin⧹isosakuranetin and eriodictyol-7,3′-dimethyl ether⧹eriodictyol-7,4′-dimethyl ether.

CHLOROSULFONATION OF FLAVONES

The chlorosulfonation of flavone and 4′-methoxyflavone with chlorosulfonic acid occurs regioselectively in ring B. The chlorosulfonyl flavones were converted into their corresponding sulfonamides and sulfonates by reaction with alkylamines, anilines, isopropyl alcohol and p−chlorophenol. Two-dimensional (COSY and HETCOR) and one-dimensional selective INEPT experiments were carried out in order to unequivocally assign all the signals in the NMR spectra of compounds.

Synthesis and Conformational Characteristics of Inherently Chiral Monoalkyl Ethers of p-tert-Butyldihomooxacalix[4]arene.

The synthesis of four inherently chiral monoalkyl ethers (methyl, ethyl, allyl, and benzyl), derived from p-tert-butyldihomooxacalix[4]arene, is described. Their conformational features were studied by variable temperature (1)H NMR spectroscopy in solvents with different polarity, such as chloroform (or CDCl(2)CDCl(2)), acetone, DMSO, and pyridine. Coalescence temperatures and DeltaG() were determined in CDCl(2)CDCl(2) and pyridine solutions. Monomethyl ether has a T(c) of 86 degrees C in CDCl(2)CDCl(2) and of -8 degrees C in pyridine, and the other derivatives are conformationally immobilized (DeltaG() >> 20 kcal mol(-1) in both solvents). The cone conformation, obtained for all monoethers, was confirmed by (13)C and NOESY spectra and also from a series of NOE 1D experiments. Complete assignment of both proton and carbon NMR spectra was achieved for the monomethyl ether by a combination of COSY, HMQC, and selective INEPT experiments, in chloroform at room temperature. Inherent chirality for all compounds was demonstrated by the addition of Pirkle's reagent to CDCl(3) solutions of monoethers derivatives, causing duplication of the NMR proton signals.

Dioclenol, a minor flavanonol from the root-bark of Dioclea grandiflora

Further investigation of the root-bark of Dioclea grandiflora resulted in the isolation of a minor constituent, dioclenol. The structure of dioclenol was determined to be 3,5,7-trihydroxy-8-methoxy-6-prenylflavanone on the basis of its spectral characteristics. The 13C NMR assignments have been confirmed by a selective INEPT experiment.

Assignment of Carbon-13 and Proton Nuclear Magnetic Resonance Spectra of Madeirane Triterpenes

The assignments of 13C and 1H NMR spectra for madeirane triterpenes are reported. The assignments were made on the basis of two-dimensional homonuclear 1H, 1H (COSY) and of 1H detected 1H, 13C heteronuclear correlation (HMQC) and also from a series of one-dimensional selective INEPT experiments. © 1997 by John Wiley & Sons, Ltd.

Study of the acid-catalyzed isomerization of dihydroveatchine.

A study of the acid-catalyzed isomerization of dihydroveatchine (5) resulted in the isolation of a single major compound, the aldehyde 6. Structure 6 has been derived from its spectral data. Reduction of 6 with NaBH4 gave compound 7, which was characterized through detailed NMR studies including 1D, 2D, and selective INEPT experiments, as well as preparation of its mono- and bis(p-nitrobenzoyl) derivatives 8 and 9. A plausible mechanism for the formation of 6, derived from the spectral data of the isomerized product obtained by deuterium labeling, is reported. Interestingly, the acid-catalyzed isomerization products of the allylic alcohols garryfoline (1) and dihydroveatchine (5) are different and appear to be dependent on the configurational orientation of the C(15) hydroxyl group. Unambiguous NMR chemical shift assignments for 5 are also reported.

Synthesis of bicarbocyclic dideoxynucleosides as potential antiviral agents

Two novel classes of bicarbocyclic dideoxynucleosides have been synthesized for antiviral studies. The key intermediates, 9 and 23, synthesized in multiple steps from readily available monocyclic or bicyclic precursors, were coupled with the desired heterocyclic bases to afford, after further elaboration, the corresponding bicarbocyclic dideoxynucleosides. The structure and stereochemistry of the tosylate intermediates and the target bicarbocyclic dideoxynucleosides were confirmed by extensive 1H and 13C NMR studies including COSY, NOESY, DEPT, and selective INEPT experiments.

Flavans and A-type proanthocyanidins from Prunus prostrata

A new natural dimeric A-type proanthocyanidin and two new monomeric flavanols have been isolated from Prunus prostrata and identified as ent-epiafzelechin (2 α → O → 7, 4 α → 8) quercetin, 5,7,2′,5′-tetrahydroxy-(2 R,3 R)- flavan-3-ol and, 7-methoxy-(+)-catechin, respectively. The structurally related metabolites ent-epiafzelechin (2 α → O → 7, 4 α → 8) afzelechin, ent-epiafzelechin (2 α → O → 7, 4 α → 8) kaempferol, ent-epiafzelechin (2 α → O → 7, 4 α → 8) epicatechin, ent-epiafzelechin (2 α → O → 7, 4 α → 8) epiafzelechin, ent-epiafzelechin (2 α → O → 7, 4 α → 8) catechin, (+)-catechin and (−)-epicatechin were also isolated. Structure elucidation was achieved by extensive NMR (homo- and hetero-nuclear two-dimensional correlation, NOE difference, and selective INEPT experiments) and CD studies.

Sch 53823 and Sch 53825, novel fungal metabolites with phospholipase D inhibitory activity

Two novel phospholipase D (PLD) inhibitors, Sch 53823 ( 1) and Sch 53825 ( 2), were isolated from a fungal culture. The acetylated derivatives, Sch 53827 ( 3) and Sch 53829 ( 4), were prepared for the purpose of structure determination. The extensive NMR studies of 3 and 4 including DEPT, COSY, NOESY, HETCOR, and selective INEPT experiments permitted the establishment of their structures, as well as relative stereochemistries. Among these compounds, 3 exhibited the most potent inhibitory activity in the phospholipase D assay with the IC 50 = 17 μM.

Cercophorins A-C: novel antifungal and cytotoxic metabolites from the coprophilous fungus Cercophora areolata.

Cercophorins A-C (3-5), three novel isocoumarin derivatives with antifungal and cytotoxic activities, have been isolated from the coprophilous fungus Cercophora areolata (JS 166 = UAMH 7495), a colonist of porcupine dung. Two additional new isocoumarins, decarboxy-citrinone (1) and 4-acetyl-8-hydroxy-6-methoxy-5-methylisocoumarin (2), and a known tricothecene mycotoxin, roridin E (6), were also obtained from this species. Compounds 1-6 were isolated from ethyl acetate extracts of mycelia and liquid cultures of C. areolata through bioassay-guided fractionation and are the first metabolites to be reported from a member of the genus Cercophora. Their structures were assigned on the basis of MS, selective INEPT, and 2D-NMR experiments.

Extensive 1D, 2D NMR Spectra of Some [7.0]Metacyclophanes and X-ray Analysis of (±)-Myricanol

From the hexane extract of the bark of Myrica cerifera, the pentacyclic triterpenes taraxerol and myricadiol were isolated. The EtOH extract afforded the [7.0]metacyclophanes, (±)-myricanol (4), and myricanone (7). Accurate 1 H- and 13 C-NMR spectral assignments have been made for (±)-myricanol (4), 5,11,17-tri-O-acetyl-(±)-myricanol (5), 11-O-methyl-(±)-myricanol (6), and myricanone (7) by a study of the 1 H- 1 H-COSY, 1 H- 13 C-COSY (HETCOR), selective INEPT, and 1D NOE experiments. The structure of (±)-myricanol was established by a single crystal X-ray analysis. Molecular mechanics MM-3(94) calculations have been made for (R,Sa)-and (S,Sa)-myricanol, and the bond lengths, bond angles, and the torsion angles have been calculated for the energy-minimized conformation

Approaches to novel bicarbocyclic nucleosides

Approaches to the synthesis of a novel family of carbocyclic nucleosides of potential anti-HIV interest have been developed. The key carbocyclic intermediate 9 was coupled with desired heterocyclic bases to give the corresponding bicyclic nucleosides. The structure of compound 9 and the bicarbocyclic dideoxynucleosides were confirmed by extensive 1H and 13C NMR studies including COSY, NOESY, DEPT and selective INEPT experiments.

Hydroxybenzoic acids from Boreava orientalis

A new guaiacylglycerol ether, threo-guaiacylglycerol-8′-vanillic acid ether, pyrocatechuic acid, pyrocatechuic acid 3- O- β-d- glucoside, gentisic acid, gentisic acid 5- O- β-d- glucoside, vanillic acid and vanillic acid 4- O- β-d- glucoside were identified from fruits of Boreava orientalis. Structural elucidation was carried out on the basis of UV, mass, 1H and 13C NMR spectral data, including 2D shift-correlation and selective INEPT experiments.

Prenylated lignans from Haplophyllum ptilostylum

In addition to previously isolated coumarins and lignans, we have obtained one new aryltetralin lignan and three new prenylated diarylbutyrolactone lignans from the aerial parts of Haplophyllum ptilostylum. The structures of the new compounds were established by 1H NMR, 13C NMR (BB and DEPT), COSY, HETCOR, COLOC and selective INEPT experiments.

Amino-Imino Tautomerization of N2-(4-n-Butylphenyl)-2'-deoxy-3,5'-cycloguanosine

P-(4-n-Butylphenyl)-2'-deoxy-3,5'-cycloguanosine (cBuPdG) has been studied by one-dimensional 1H and 13C, two-dimensional TOCSY, HMQC, and HMBC, and long range selective INEPT NMR experiments. In DMF and DMSO solutions cBuPdG exists as a mixture of two isomers involved in a slow rate of interconversion which have been identified as N2 amino-imino tautomers, while in chloroform only the imino tautomer is present. It has been proved that the tautomeric form of the parent nucleoside, P-(4-n-butylphenyl)-2'-deoxyguanosine (BuPdG), is N2 amino. The selective INEPT experiment can be used efficiently in assignment of tautomeric structures of nucleosides. P-Phenylguanines and their nucleoside derivatives show interesting and important biological properties. lg2 For example P-(4-n-butylphenyl)-2'-deoxyguanosine

A Utilization of the Selective Inept Experiment for the Structure Elucidation of Oxygenated Chromenes

Abstract A utilization of the selective INEPT experiment in which polarization transfer is effected through the chelated hydroxyl groups is described for the structure elucidation of two isomeric chromene derivatives, drummondin C (1) and isodrummondin C (2) from Hypericum drummondii (Grev. & Hook.) T. & G.

Revision of the NMR Assignments of Pterostilbene and of Dihydrodehydrodiconieferyl alcohol: Cytotoxic Constituents fromAnogeissus acuminata

Abstract Further phytochemical work on Anogeissus acuminata var. lanceolata (Combretaceae) led to the isolation of pterostilbene (1), dihydrodehydrodiconiferyl alcohol (2), and conocarpan (3). The structure of these compounds were determined by spectroscopic means, mainly through 1D and 2D NMR experiments. A revision of some of the 13C NMR chemical shifts of 1 and 2 were made possible by HETCOR, FLOCK, and selective INEPT experiments. Homonuclear spin-decoupling and 1H-1H COSY experiments also enabled the precise assignment of the 1H NMR chemical shifts of 2. Compounds 1–3 exhibited in vitro cytotoxicity in various cancer cell lines. This is the first isolation of 1–3 from Anogeissus.