HETCOR Experiments Research Articles

N-oxides of some norditerpenoid alkaloids.

Eight new N-oxides [1-8] of the norditerpenoid alkaloids aconitine, ajacine, delphinine, delphisine, deltaline, heteratisine, lappaconitine, and N-deacetyllappaconitine have been prepared with m-chloroperbenzoic acid. The structures of these compounds were established on the basis of their spectroscopic data (1H, 13C, DEPT, COSY, HETCOR, and selective INEPT nmr experiments). The complete nmr chemical shift assignments for all eight N-oxides are reported. Table 2 shows the differences between the 13C-nmr shifts of the N-oxides compared with those of the parent alkaloids.

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.

Synthesis and fluxional behaviour of allylpalladium complexes with poly (pyrazol-1-yl)methane ligands

The reaction of the solvento-complex [(ν 3-2-McC 3H 4)Pd(S) 2]X (S = Me 2CO) with the stoichiometric amounts of the following poly(pyrazol-1-yl)methanes: bis(pyrazol-1-yl)methane (bpzm), bis(3,5-dimethylpyrazol-1-yl)methane(3,5-Me2bpzm), tris(pyrazol-lyl)methane (tpzm) and tris(3,5dimethylpyrazol-1-yl) methane (3,5-Me 2-tpzm) leads to the cationic complexes [(ν 3-C 4H 7)Pd(bpzm)]BF 4, (1), [(ν 3-C4H,)Pd(bpzm)]PF6, ( 2), [(ν 3-C 4H 7)Pd(tpzm)]B F4, (3), [(ν 3-C 4H 7)Pd(3,5-Me 2bpzm)]PF 6, (4), and [(ν 3_ C 4H 7)Pd(3,5Me 2tpzm)]PF 6, ( 5). Resonances in the 1H NMR spectra have been assigned by considering the NOE effects between the methylene or methyne protons and the H( 5) or Me(5) groups. NOE effects have also been observed between the H(3) or Me(3) and the H(syn) allylic protons. The 13C NMR resonances have been assigned using 1H- 13C HETCOR experiments. The fluxional behaviour of 4 and 5 has been studied by 1 H NMR spectroscopy. Two conformers of 4 are discernible at low temperature, and they interchange when the temperature is increased. The AB systems corresponding to methylene groups of both conformers coalesce to a single A, system. A mechanism is proposed on the basis of this observation and the activation free energies at the coalescence temperature calculated. The 1H NMR spectrum of 5 shows the equivalence of the coordinated and uncoordinated pyrazole rings. The energy barrier of this phenomenon is too low to be determined by NMR spectroscopy. A tumbling motion, as proposed for similar observations, seems a likely pathway of exchange.

Novel three-dimensional 1H-13C-31P triple resonance experiments for sequential backbone correlations in nucleic acids.

Backbone-driven assignment methods that utilize covalent connectivities have greatly facilitated spectral assignments of proteins. In nucleic acids, 1H-13C-31P correlations could play a similar role, and several related experiments (HCP) have recently been presented for backbone-driven sequential assignments in RNA. The three-dimensional extension of 1H-31P Het-Cor (P,H-COSY-H,C-HMQC) and Het-TOCSY (P,H-TOCSY-H,C-HMQC) experiments presented here complements HCP experiments as tools for spectral assignments and extraction of dihedral angle constraints. By relying on 1H-31P rather than 13C-31P couplings to generate cross peaks, the strongest connectivities are observed in different spectral regions, increasing the likelihood of resolving spectral overlap. In addition, semiquantitative estimates of 1H-31P and 13C-31P couplings provide dihedral angle constraints for RNA structure determination.

Regioselective Pd-mediated coupling between 2,6-dichloropurines and organometallic reagents

Selective coupling in the purine 6-position has been achieved, by reacting N-benzylated 2,6-dichloropurines with organotin and organozinc reagents. The positional identity products were established from long range HETCOR or nOe NMR experiments.

1H and 13C NMR studies on 5,11-dimethyl-5 H-indolo[2,3-b]quinoline and some of its derivatives

The 1H and 13C NMR spectra of the parent 5-methyl-5 H-indolo[2,3 b-quinoline] and 5,11-dimethyl-5 H-indolo[2,3 b]quinoline and nine various methyl, methoxy and fluoro derivatives of the latter have been measured and analysed by the use of COSY, HETCOR, COLOC and selective decoupling experiments. This gave unambiguous assignment of all signals in the spectra studied; proton-proton coupling constants across three, four and five bonds have also been determined. The most interesting result found concerns a very large increase in the shielding of carbon 1 upon introduction of a methyl group at C11. This effect is dramatically enhanced by subsequent substitution with a methoxy group at C2.

Two new norditerpenoid alkaloids from Delphinium elatum var. "black night".

Two new norditerpenoid alkaloids, blacknine [1] and blacknidine [2], have been isolated from the whole plants of Delphinium elatum var. "black night" along with six known alkaloids. The structures of the new alkaloids 1 and 2 were derived from their spectroscopic data (1H, 13C, DEPT, COSY, HETCOR, and selective INEPT nmr experiments). The phytochemistry of this plant variety has not been examined previously.

A taxoid from needles of himalayan Taxus baccata

13-Acetyl-13-decinnamoyltaxchinin B, a taxoid having a rearranged 11(15 → 1) abeo-taxane skeleton, has been isolated from the needles of the Himalayan yew, Taxus baccata. The compound has not previously been encountered in nature. Its structure was established by 1- and 2D NMR techniques including DQF-COSY, HETCOR and HMBC experiments. The conversion of 13-decinnamoyltaxchinin B, a known taxoid, to 13-acetyl 13-decinnamoyltaxchinin B confirmed the structure of the latter.

1H and13C NMR studies of 6,11-dimethyl-6H-indolo[2,3-b] quinoline and some of its derivatives

The 1H and 13C NMR spectra of the parent 6,11-dimethyl-6H indolo[2,3-b]quinoline and of its nine 2- and 9- methyl-, methoxy- and fluoro-substituted derivatives have been measured and analysed by the use of cosy, HETCOR, SPT INEPT and selective decoupling experiments. The INADEQUATE experiment was applied to yield the one-bond 13C–13C coupling constants for most of the compounds studied. Proton–proton coupling constants including long-range ones have also been determined. Strong concentration effects on the spectra have been observed for all the compounds studied. In particular, large upheld shifts upon the increase of concentration have been observed for some proton resonances. This has been explained in terms of self association of the compounds.

13C nuclear magnetic resonance analysis of two prenyl flavonols from platanus acerifolia buds

AbstractThe carbon nuclear magnetic resonance (NMR) data of the acetyl derivatives of 8‐(1,1‐dimethyl‐2‐propen‐1‐y1) galangin and 8‐(1,1‐dimethyl‐2‐propen‐1‐yl) kaempferide, isolated from Platanus acerifolia buds, have been reassigned unambiguously by HETCOR and COLOC experiments on synthetic compounds. The carbon NMR data for the naturally occurring 8‐(1,1‐dimethyl‐2‐propen‐1‐yl) kaempferide is reported for the first time.

Total assignment of the 1H and 13C chemical shifts for a mixture of cis‐ and trans‐p‐hydroxycinnamoyl esters of taraxerol with the aid of high‐resolution, 13C‐detected, 13C1H shift correlation spectra

AbstractA mixture of two slowly interconverting isomeric compounds was isolated from Bernardia laurentii and identified as the trans‐ and cis‐p‐hydroxycinnamoyl esters of the triterpene taraxerol. Their 13C and 1H NMR spectra were totally assigned with the aid of concerted two‐dimensional NMR experiments. Not all assignments could be made using HMQC and HMBC owing to the limited 13C resolution and severe spectral crowding. However, the assignments could be made unambiguously by HETCOR and FLOCK experiments, relying on the superior 13C resolution of the 13C‐detected experiments. Comparison of 13C spectral assignments for a series of eight pentacyclic triterpenes with identical A and B ring structures but differences in C, D and/or E rings illustrates the risks and limitations of the use of model compounds for spectral assignments.

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.

13C NMR spectra of allosteric effectors of hemoglobin

AbstractCarbon‐13 NMR studies were performed for a series of allosteric effectors of hemoglobin. Spectral assignments were made by comparison of 1H‐decoupled 13C spectra; for selected cases, 2D HETCOR experiments were applied. High regularity in the chemical shifts of the similar fragments of these structures was found.

Two Dimensional NMR Study of Aspidospermine

Abstract Two dimensional COSY, HETCOR and inverse HMBC experiments were performed on a natural alkaloid, Aspidospermine, which allowed complete 1H and 13C spectral assignments to be made. These results suggest that the reversal of certain 13C literature assignments of related compounds is required.

1H- and 13C-Nmr Assignments of Phyllanthin and Hypophyllanthin: Lignans That Enhance Cytotoxic Responses with Cultured Multidrug-Resistant Cells

Complete 1H-nmr data and unambiguous assignments of the 13C-nmr spectra of phyllanthin [1] and hypophyllanthin [2] were obtained through extensive nmr studies, including homonuclear COSY, homonuclear decoupling, APT, HETCOR, nOe difference, selective INEPT, and COLOC experiments. The absolute configuration of hypophyllanthin [2] was determined by cd. Neither of these lignans demonstrated significant cytotoxic activity when evaluated with a battery of cultured mammalian cells, but both were found to enhance the cytotoxic response mediated by vinblastine with multidrug-resistant KB cells. In addition, 1 was found to displace the binding of vinblastine with membrane vesicles derived from this cell line, suggesting an interaction with the P-glycoprotein.

6-Deoxyclitoriacetal from Clitoria macrophylla

A new rotenoid, 6-deoxyclitoriacetal, was isolated from the roots of Clitoria macrophylla and its structural assignment was established unambiguously by a series of HETCOR, COLOC and NOE difference experiments. In vitro tests showed that this compound possessed strong cytotoxic activity against cultured P-388 lymphocytic leukemia cells, but was not active with cultured KB cells. However, marginal activity was observed with vinblastine-resistant KB-V1 cells, and this was enhanced by the addition of vinblastine. This rotenoid may, therefore, interact with P-glycoprotein.

Structure establishment by two‐dimensional NMR spectroscopy of the product obtained in the reaction of MCPBA and himachalol and revised 1H NMR assignments for himachalol

AbstractThe reaction of himachalol with m‐chloroperoxybenzoic acid afforded a rearrangement product, the structure of which was deduced by 2D NMR analysis to be 3α,4α‐epoxyhimachalane‐2α,7α‐diol. The recently proposed 1H NMR assignments for himachalol have been revised, based on the analysis of 2D COSY, DEPT, HETCOR and NOE experiments.

Stevisalioside A, a novel bitter-tasting ent-atisene glycoside from the roots of Stevia salicifolia.

A new acetylated ent-atisene glycoside, stevisalioside A [1], has been isolated as a bitter-tasting principle from Stevia salicifolia roots. The structure was established by the interpretation of spectral data, with the nmr assignments of this compound being based on 1H-1H COSY, 1H-13C HETCOR, and selective INEPT experiments. A rearrangement product 4 of the aglycone moiety obtained by alkaline hydrolysis supported the structure of 1. This is the first report of the occurrence of an atisane-type diterpene from the genus Stevia.

Three new D-ring unsaturated sterols from the Mediterranean sponge Topsentia aurantiaca: Structure determination and complete nuclear magnetic resonance assignment

Three novel sterols with a rare D-ring unsaturation were isolated from the marine sponge Topsentia aurantiaca and identified as 5α-cholest-14-ene-3β,16α-diol ( 2), 24R- ethyl-5α-cholest-14-ene-3β,16α-diol ( 3), and 24S- ethyl-5α-cholest-14-ene-3β,16a-diol ( 4). The sponge also elaborates a further D-ring unsaturated sterol, 5α-cholest-15-en-3β-ol ( 1), which has been previously described only as a synthetic product. All the 1H and 13C nuclear magnetic resonances of compounds 1 and 2 were assigned to the relevant protons and carbons by bidimensional COSY, HETCOR, and HMQC nuclear magnetic resonance experiments.

X-ray crystal structure determination and NMR solution studies of 3′,3″5′,5″-tetrabromophenolphthalein ethyl ester

The crystal structure of 3′,3″,5′,5″-tetrabromophenolphthalein ethyl ester (TBPE) has been determined by X-ray diffraction at room temperature. This compound crystallizes in space group [Formula: see text], with a = 12.361(4), b = 12.533(4), c = 9.986(2) Å, α = 99.57(3), β = 112.76(2), γ = 100.73(3) °, and Z = 2. The structure was solved by direct methods and refined by full-matrix least-squares calculations to a residual of 0.034 for 1862 observed reflections. TBPE is propeller shaped about the central carbon and crstallizes with one molecule of benzene solvent per asymmetric unit. In 1:1 CD2Cl2:CDCl3 solution complete 1H and 13C NMR signal assignments have been made via 1H1H COSY and 1H13C HETCOR experiments. The quinoidal and phenolic integrities are retained on the NMR timescale. By contrast for an acetone-d6 solution only 14 13C resonances are found and the colour of the solution changed from green to dark blue. These changes in acetone solution are attributed to the presence of a trace of base which induces the loss of the phenolic proton of TBPE and the existence of resonance forms which render the phenolic and quinoidal rings equivalent. Key words: crystal structure, NMR, 3′3″5′5″-tetrabromophenolphthalein ethyl ester.