HSQMBC

Figure 36 Pulse sequences for the CBC-HSQMBC experiment. Narrow and thick bars represent 90° and 180° RF pulses, respectively. Pulse phases are along x unless indicated otherwise. Phase cycles are (pn = x, x

Another interesting possibility relies on the recording of two complementary IP and AP data separately and then added/subtracted to provide spin-state-selective a//1-HSQMBC spectra.119 In these types of IPAP spectra, the magnitude of "Jch can be directly determined by simple analysis of the relative displacement between a- and /1-cross-peaks. 

Other strategies that show great promise in reducing NMR acquisition time utilise methods to obtain multiple sets of data from one experiment through a concept known as time-shared evolution. An example of this process that should find utility in natural products elucidation was demonstrated by a pulse sequence called CN-HMBC.93 Traditionally, a separate 13C-HMBC and 15N-HMBC were acquired independently. However, the CN-HMBC allows both 13C- and 15N-HMBC spectra to be obtained simultaneously. By acquiring both data sets simultaneously, an effective 50% time reduction can be achieved.93 This approach has also been demonstrated for a sensitivity-enhanced 2D HSQC-TOCSY (heteronuclear multiple bond correlation total correlation spectroscopy) and HSQMBC (heteronuclear single quantum... 

R. T. Williamson, B. L. Marquez, W. H. Gerwick, and K. E. Kover, One- and two-dimensional gradient-selected HSQMBC NMR experiments for the efficient analysis of long-range heteronuclear coupling constants, Magn. Reson. Chem., 38 (2000) 265-273. 

More recently, a gradient-enhanced heteronuclear single quantum multiple bond correlation (HSQMBC) experiment and its variants34,47,60-62 have been proposed for the measurement of heteronuclear coupling... 

Their work was based, in part, on the ID HSQC-TOCSY experiment. In general, the authors have utilized the Preservation of Enhanced Pathways (PEP) approach in the development of the sequences that they have described. The HSQC-TOCSY based experiments, of course, mandate a protonated resonance. The authors have, however, also proposed a HSQMBC experiment in which the heteronuclear... 

Now a simple, general and pratical method is available for direct measurement of V(ch) coupling constants [73]. ID and 2D heteronuclear single quantum multiple bond correlation (HSQMBC) experiments are easily performed in a routine manner. These experiments are based on the evolution of heteronuclear single quantum coherence (SQC) in... 

HSQMBC = Heteronuclear Single Quantum Multiple Bond Correlation... 

In 2001, Meissner and Sprensen described methods for the measurement of Jhh anO "Jch couplings employing the broadband excitation approach (see Section 3.3.7) with the report of the broadband XLOC and broadband J-HMBC experiments, respectively. In a further extension of the idea of accordion optimization, Williamson ef reported the development of the J-IMPEACH-MBC pulse sequence. This approach is similar to the EXSIDE experiment previously described by Krishnamurthy and the J-resolved HMBC experiments of Furihata and Seto"- in its use of J-scaling to render small, long-range heteronuclear couplings conveniently measurable. Finally, Williamson e/ also described a new method, G-BIRDr-HSQMBC, that was reported in their survey of the available methods. 

Since being reported in 2000, the HSQMBC experiment has been applied to a number of complex structural analyses." The authors initial demonstration of the technique employed sucrose, strychnine (14) and the complex marine natural... 

Long-range heteronuclear coupling constants determined from HSQMBC spectra were also used in the J-based conformational analysis - of the aliphatic stereocenters at C7 through CIO of the neurotoxin kalkitoxin (28) from the marine cyanobacterium Lyimgba majuscula ... 

Phormidolide (29) the complex marine cyanobacterial metabolite used as one of the examples in the initial report describing the HSQMBC experiment," is the subject of a recent report. It is noteworthy that during the J-based conformational analysis of phormidolide that the authors had an unprecedented five conformational restraints (homo- and heteronuclear couplings, NOE. and ROE) per stereocenter. 

Finally, Moore and co-workersreported using a combination of HETLOC and HSQMBC experiments to measure the long-range heteronuclear coupling constants of apratoxin A (30), a cytotoxin from the marine cyanobacterium Lyngba majuscula. 

Unambiguous resonance assignments of diastereotopic CH2 protons in the anomeric side chain of nine alkyl- and aralkylselenoglycosides have been carried out by Rusakov et u/. " on the basis of experimental CPMG-HSQMBC measurements and theoretical SOPPA calculations of... 

Figure 3 LR-HSQMBC pulse sequence [24]. The experiment is analogous to the...

Figure 4 LR-HSQMBC spectrum of strychnine optimized for 2 Hz [24]. The data...

Scheme 1 Structure of strychnine (2) showing correiations observed in the 2 Hz optimized LR-HSQMBC spectrum shown in Fig. 4 [24]. When both anisochronous protons exhibited correiations, e.g., Ila/b, both protons are specified otherwise, the specific proton exhibiting the correiation, e.g., HI 5a, is noted. Dashed arrows denote weaker correiations. Red (gray shade in the print version) arrows denote Jch correiations pre-viousiy unobserved in HMBC or accordion-optimized heteronudear shift correiation experiments used for observing iong-range H- N correiations.

R.T. WiUiamson, A.V. Buevich, G.E. Martin, T. Parella, LR-HSQMBC a high sensitivity technique to probe very long-range heteronuclear coupling pathways, J. Org. Chem. 79 (2014) 3887-3894. 

Recent Advances in Small Molecule NMR Improved HSQC and HSQMBC Experiments... 

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