HMQC- NMR experiments

Figure 4 (A) The standard S l CP/MAS NMR experiment, (B) the multiCP experiment, (C) the MELODI-HETCOR NMR experiment, and (D) the MAS-J-HMQC NMR experiment with 0 denoting the magic angle, ca. 54.7°. In general, different time periods are not drawn to scale. For phase cycling schemes we refer to original articles.

Applications Useful 2D NMR experiments for identification of surfactants are homonuclear proton correlation (COSY, TOCSY) and heteronuclear proton-carbon correlation (HETCOR, HMQC) spectroscopy [200,201]. 2D NMR experiments employing proton detection can be performed in 5 to 20 min for surfactant solutions of more than 50 mM. Van Gorkum and Jensen [238] have described several 2D NMR techniques that are often used for identification and quantification of anionic surfactants. The resonance frequencies of spin-coupled nuclei are correlated and hence give detailed information on the structure of organic molecules. 

A variety of examples of 2D-NMR experiments is provided in reference [21]. The structure elucidation of the di-rhodium compound shown in Figure 11.3 was mostly carried out in this way. For example, 2D 11 l-31P heteronuclear multiple quantum correlation (HMQC) experiments were used to show that two rhodium-coupled hydride resonances are connected to a single type of 31P nucleus. 

The second Chilocorini species studied, Chilocorus cacti, contained several alkaloids closely related to the former. The structure of the heptacyclic chilo-corine A (19) was deduced from a series of NMR experiment (DEPT, HMQC, DQ-COSY, TOCSY) and from a comparison of its spectral properties with those of exochomine (18) from which it differ by having two C-C linkages between the two tricyclic partners. However, the configuration at the asymmetric center in the azaacenaphthylene ring was not established [33]. 

In this study the alkaloids were separated by centrifugally accelerated radial TLC (Chromatotron) using Al O plates (E. Merck Art 1092), and further cleaned on preparative TLC plates. The stmctures were determined by ID and 2D NMR experiments including H- H COSY, HMQC, HMBC and NOESY. The new compounds were cochleareine (9) C and the other acoleareine (10) C alkaloids. 

Inverse-detected experiments have had the greatest effect in making 15N NMR experiments feasible for small samples. These experiments take advantage of the higher sensitivity of NMR to facilitate the observation of insensitive nuclei like 13C and 15N. The H-13C heteronuclear multiple quantum coherence (HMQC) and the related heteronuclear multiple-bond correlation (HMBC) experiments are important in contemporary natural products... 

The amount of sample used is also an important consideration in preparing samples. At very high concentrations, the sample can become very viscous and spectral resolution will diminish. The authors have found that a concentration of -50-100 mg ml1 provides good sensitivity and resolution for ID and 2D NMR experiments carried out using 5-mm tubes and field strengths of 300-900 MHz. However, should the amount of sample be restricted, useful information can still be obtained from 2D NMR experiments, as demonstrated by Haiber et al. (1999), who obtained HMQC (3H-13C one bond correlation) data using sample concentrations less than 30 mg ml1. 

Figure 15.1. (A) COSY, (B) TOCSY, (C) 1H-1T HSQC or HMQC, (D) dl- Y HMBC, for 4-oxopentanal. For clarity, only key assignments have been given as an example. Note that the double-ended arrows indicate how to interpret the spectra. In the case of COSY and TOCSY the information is represented as cross-peaks that are symmetrically oriented with respect to the central diagonal. In the single-bond correlation (HSQC/HMQC) a cross-peak represents in one dimension the carbon chemical shift and in the other dimension the proton chemical shift. Note there is no diagonal in heteronuclear NMR experiments. In the HMBC, lines are drawn vertically to connect the cross-peaks. In HMBC 2-4 bonds, H-13C correlations are often observed. Note that the 4-bond correlation is less common in NMR but has been included here as an example, and 1-bond correlation is commonly filtered from the HMBC experiment to improve detection limits for the weaker 2-4 bond correlations.

In 1989, the first applications of multidimensional NMR were applied to humic substances (Buddrus et al., 1989).This study involved the application of 13C detected J-resolved (J-Res) spectroscopy. The study was successful in that it showed multidimensional NMR was applicable to the study of humic substances. However, in 1989 the lack of various modern experiments and the corresponding hardware (mainly probes fitted with pulse field gradients) made applying NMR to humic materials very challenging. In 1997, Simpson et al. demonstrated that the more sensitive inverse-detected NMR experiments were applicable to NOM (Simpson et al., 1997). In this manuscript COSY,TOCSY and HMQC were applied (Simpson et al.,... 

A 2002 review by Reynolds and Enriquez describes the most effective pulse sequences for natural product structure elucidation.86 For natural product chemists, the review recommends HSQC over HMQC, T-ROESY (transverse rotating-frame Overhauser enhancement) in place of NOESY (nuclear Over-hauser enhancement spectroscopy) and CIGAR (constant time inverse-detected gradient accordion rescaled) or constant time HMBC over HMBC. HSQC spectra provide better line shapes than HMQC spectra, but are more demanding on spectrometer hardware. The T-ROESY or transverse ROESY provides better signal to noise for most small molecules compared with a NOESY and limits scalar coupling artefacts. In small-molecule NMR at natural abundance, the 2D HMBC or variants experiment stands out as one of the key NMR experiments for structure elucidation. HMBC spectra provide correlations over multiple bonds and, while this is desirable, it poses the problem of distinguishing between two- and three-bond correlations. 

FIGURE 12.16 Pulse sequence for the triple resonance 3D NMR experiment HNCO. H and N denote H and 15N, C denotes 13C=0, and K denotes 13C . Pulses at times 1, 2, and 3 constitute an INEPT sequence that transfers coherence from H to. V, where it precesses during q. Pulses at times 6, 7, and 8 represent an HMQC sequence that creates multiple quantum coherence in C (where it precesses during and transfers coherence back to N. Pulses 10 and 11 are an inverse INEPT sequence that transfers coherence back to H for detection during f3.The other 180° pulses refocus heteronuclear spin couplings. Note that coherence is not transferred to spin K. 

A complex, multiply bridged 1,2,3,4-adduct of C60 (168) (Scheme 1.11) including a noninherently chiral addition pattern as well as a multitude of stereogenic centers in the addend moiety was obtained in a tandem reaction between the alkaloid scandine and Ceo-324 The sequence included a photoin-duced addition of the tertiary amine subunit of the alkaloid and a [2 + 2] cycloaddition of its vinyl group to the adjacent intrahexagonal formal double bond of the fullerene. The structural elucidation included 1H-1 H COSY-, HMQC- (heteronuclear multiple quantum coherence), HMBC-, and ROESY-(rotating frame Overhauser enhancement spectroscopy) NMR experiments and... 

Stractnral conhrmation and complete NMR assignments were accomplished by 3D PFG NOESY-HMQC experiments nsing a C-emiched sample (Satake et al. 1995). Althongh the 3D NMR techniqne has become a rontine method for studies of protein and nucleotide, apphcations to natural products are rate. Unlike proteins, it is very difficult to enrich marine natural products with more than 90% abnndance. Moreover, the stractural elucidation of most natural products can be accomplished by 2D NMR experiments. MTX needed 3D NMR experiments becanse more than 200 proton signals give rise to over 2000 cross peaks in the 2D NOESY spectra. 

HMQC) or single (HSQC) quantum coherence during the t evolution period. The sensitivity of any NMR experiment is proportional to the gyromagnetic ratios of the starting and the detected spins as YstartYdetect - For HMQC and... 

With suitable modification of the pulse sequences the para-hydrogen effect can be used to enhance the signals in many NMR experiments, for example, COSY, HMQC, HSQC, EXSY and Overhauser spectroscopy. ... 

The structures of the natural products, ceratospongamides from marine red alga (Rhodophyta) Ceratodictyon spongiosum, which each consist of two L-phenylalanine residues, one (L-isoleucine)-methyloxazoline residue, one L-proline residue, and one (L-proline)thiazole residue, were established through extensive NMR experiments, including heteronuclear multiple quantum correlation total correlated spectroscopy (HMQC-TOCSY), and... 

A few phosphoramidites have been used to prepare 5 -modified ODNs. The synthesis of a 5 - C-labeled ODN has been described to enable NMR analysis by 2D HMQC NOESY experiments. A formamidine-protected... 

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