Heteronuclear 2D NMR

Covariance processing can also be applied to heteronuclear 2D NMR experiments. As first demonstrated in a report by Zhang and Briishwei-ler,82 an "indirect" covariance spectrum can be obtained by multiplying a spectrum by its transpose according to Equation (2) ... 

Schwartz and co-workers, also at Merck, reported the isolation and elucidation of the structure of pramanicin (12) and a related fatty acid that were discovered during a search for novel antifungal agents.60 The authors reported using a 500 MHz 3 mm micro-inverse probe for the acquisition of the heteronuclear 2D-NMR data to characterize the molecule, including a HMQC spectrum. 

Later in 1997, Ondeyka et a/.83 reported the isolation and identification of the structure of nodulisporic acid (27) using micro-NMR probe technology. Nod-ulisporic acid is a novel insecticide from Nodulisporium sp. and was the first representative of a new class of indole terpenes to be identified. The authors used a combination of -detected homo- and heteronuclear 2D-NMR experiments to assemble the structure in conjunction with a series of three INADEQUATE, each 5 days long, optimized from 40 to 60 Hz that employed a 26 mg sample of 27. The INADEQUATE data were subjected to computer analysis,84 86 which identified 32 of 47 possible 13C-13C connectivities. 

One of the fundamental approaches to acquiring heteronuclear 2D NMR data for unknown molecules in many laboratories is to acquire data using survey spectrum conditions. For survey conditions, pre-established spectral windows are routinely used in both frequency domains. In the case of HSQC and HMBC experi-... 

Recently, workers at Abbott Laboratories reported the isolation and prelintinary characterization of a new nargenicin-type Z u-macrolide antibiotic, coloradocin, 8, from cultures of Actinoplanes coloradoensis. H The novel bislactonic structure proposed for 8 was based on a detailed spectroscopic examination which included extensive homo- and heteronuclear 2D NMR studies. 12 Although these investigations failed to unequivocally define the relative configuration of the macrocyclic chirality, the key structural elements of 8, including an oxa-bridged octalin... 

A combination of different homo- and heteronuclear 2D NMR techniques at 500 MHz have enabled complete assignment of the H and signals of the two conformers of RA-VII in CDCI3 (major conformer conformer A minor one conformer B) [94]. The structures of the two conformers (A and B) in CDCI3 were elucidated based on temperature effects on NH protons, deuterium exchange rate, vicinal coupling constants and NOE experiments (Fig. 27). These conformational analyses showed that the structure of these conformers is a result of geometrical isomerization and that the predominant conformer A exhibits a typical type II P-turn between Ala and Tyr, similar to the crystal structure as analyzed by X-ray diffraction. The minor conformer B exhibits a type VI... 

From the root bark of Zizyphus mauritiana, a new cyclopeptide alkaloid mauritine J (54), together with known alkaloids, was isolated. Its structure was established by homo- and heteronuclear 2D-NMR analysis and compared with that of amphibine E (55) (51). From Zizyphus oenoplea, some cyclopeptide alkaloids were isolated (52-54). 

Recently the method employing DNP for recording heteronuclear 2D NMR spectra of small drug-like molecules was proposed by Ludwig and coworkers [101]. This method ensures significant improvement in sensitivity due to the high spin polarization, but limits the number of points sampled in indirectly detected dimension, so the combination with the non-uniform sampling scheme was necessary. 

While the subject of 2D NMR spectroscopy may initially appear a daunting one, the simplest point of entry into 2D NMR is undoubtedly via /-resolved experiments [73, 74]. From a fundamental understanding of the segregation of spectral parameter information between frequency domains in a 2D / experiment, the reader can successfully begin to delve into homo- and heteronuclear 2D NMR techniques. 

G.E. Martin, B.D. Hilton, K.A. Bhnov, A.J. Williams, Unsymmetrical inchrect covariance processing of hyphenated and long-range heteronuclear 2D NMR spectra-enhanced visualization of 7/ch nd Jch correlation responses, J. Heterocychc Chem. 45 (2008) 1109. 

During the multidimensional NMR experiments, effective coherence transfer is important, which can be accomplished via accurate J-modulation (e.g.. Insensitive Nuclei Enhanced by Polarization Transfer, INEPT) or dipole-dipole (Nuclear Over-hauser Effect, NOE) interaction. As seen in the table, the couplings with F are quite different from those with H and The large and varied F couplings create opportunities and permit a larger variety of experiments, while at the same time, it also create complicated spectra with complex cross-peak patterns. The Vcf and Jcp in Table 24.2 is sufficient for the heteronuclear 2D-NMR experiments... 

There have been several historical evaluations to examine the ability of computer-assisted structure elucidation or CASE programs to generate the correct structure with and without the avahabihty of long-range heteronuclear 2D NMR data [31—33]. 

D. Jeannerat, High-precision heteronuclear 2D NMR experiments using 10-ppm spectral window to resolve carbon overlap, Chem. Commun. (2009) 950—952. 

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