Phase-sensitive HMBC

Long-range H- C connectivity information in the phase-sensitive HMBC spectrum (Figure 5.7) allowed the assembly of the structural fragment shown by 14. The wavy lines denote the point beyond which long-range correlations could not reach. Structural fragment 14 and an 11-cryptolepinyl moiety derived from 13 account for 31 of 32 carbons in the empirical formula of the molecule. A sole... 

DFT calculations have been used to construct new Karplus curves for 2./ m. 3/Hh (as mentioned before) 2/CH, Veil- Vnccc. 3/hcoc> and 3/hcsc- A major focus of this investigation62 was DFT computations for the exocyclic hydroxymethyl group of aldohexopyranoside derivatives, particularly in methyl a- and /i-D-gluco- and -galacto-pyranosides, for which coupling constants were also determined experimentally by 2D H -13C heteronuclear zero- and double-quantum, phase-sensitive /-HMBC NMR. DFT on methyl /1-D-glucopyranoside yielded 3/hcoc values that fitted the equation ... 

Conformational analy.si.s u.King HETLOC and phase-sensitive HMBC... 

Early reports of NMR-based configuration analysis relied on a combination of the HETLOC" " and phase-sensitive HMBC °" methods that were then available in conjunction with Jhh homonuclear coupling constant data. Quite simply. HETLOC can be employed to establish the relative stereochemistry of... 

At the time Murata s study was reported, the solution structure of acyclic portions of the okadaic acid structure were not known despite extensive NOE measurements coupled with distance geometry calculations. Using Jhh coupling constants measured from E. COSY data and "Jch (" = 2, 3), determined predominantly from HETLOC spectra for the contiguous protonated carbon portions of the molecule and phase-sensitive HMBC data for segments containing quaternary carbons, Murata and co-workerswere able to successfully establish the solution structure of okadaic acid. 

As noted in the introduction to the previous section, phase-sensitive HMBC data can be used to measure long-range heteronuclear coupling constants. 

Figure 6.27. The phase-sensitive HMBC experiment with echo-antiecho selection. The gradient ratios G1.G2 are 5 -3 and 3 -5 for odd and even experiments, respectively, when selecting carbon-13.

Figure 6.44. The phase-sensitive HMBC sequence for measuring Vch coupling constants, (a) A possible scheme for producing reference proton template multiplets (see text) and (b) the HMBC experiment.

An alternative to absolute value presentation has been proposed by Bax and Marion (1988). We have found mixed-mode processing, in which the data is absorptive in the (Fi) frequency domain and absolute-value-calculated in the proton (F2) frequency domain to provide a superior presentation of HMBC spectral data. Williamson et al. (1989) carried the idea of absorptive HMBC experiments a step further, demonstrating in the specific case of the antibiotic distamycin-A that fully phase-sensitive HMBC spectra may be recorded. 

Figure 5.6 Comparative segments from (a) conventional and (b) phase-sensitive 8-Hz optimized HMBC spectra of DP-2 recorded using a 3-mm sample positioned coaxially in a 5-mm gradient inverse triple resonance Varian Cold-probe . ...

Figure 5.7 Phase-sensitive 8-Hz optimized HMBC spectrum of degradant DP-2 recorded overnight using a 500-MHz Varian Cold-probe .

The mechanism of singlet oxygen detoxification involves quenching by Vitamin Be (215a). After silylating this compound, in order to make it soluble in CD2CI2 to work at low temperature, the quenching process proceeds as shown in equation 75 (Section V.C.4). The main product is endoperoxide 217, probably in equilibrium with hydroperoxide 216. The structure of 217 can be established from the H and NMR spectra, e.g. 5h = 6.06 ppm (IH, d, 7 = 4.4 Hz, HCOO), 4.19 (IH, broad, NH), 5c = 96.8 ppm (MeCOO), 86.6 ppm (HCOO), and DEPT, phase-sensitive COSY, HMQC and HMBC spectra . 

During the structural elucidation of the first flavone-xanthone dimer (swertifranche-side) through a series of ID or 2D NMR techniques including COSY, phase-sensitive ROESY, reversed-detected HMQC, HMBC, and selective INEPT experiments, H and C signals appeared as two peaks indicating two conformers and classically, the coalescence of the split signal was observed as the temperature was increased. 

Notably, two isomeric products can be generated. The usual infrared (IR) and mass spectra as well as H and 13C NMR chemical shifts could not define which isomer was formed. The authors used different NMR techniques, such as 2-D heteronuclear multiple bond correlation (HMBC) experiments and phase-sensitive nuclear overhauser enhancement spectroscopy (NOESY) measurements to elucidate the product s structure. 

FIGURE 24. ll detected H—29Si correlation spectra of 15 ( II frequency 600 MHz, 5 mm inverse detection broad-band probe, relaxation time 2.0 s, acquisition time 0.38 s, 64 transient for each of 64 increments). (The two non-equivalent CH2 protons are distinguished by the letters a and b.) (a) Phase-sensitive spectmm measured with HSQC constant time experiment described in text (b) magnitude presentation of HMBC spectrum. Reproduced by permission of Academic Press from Reference 212... 

It is also important that LP not be abused. A sufficient number of increments must be taken from which the FID s can confidently be extended. A total of 64 increments has, for example, been found to be insufficient, while LP s have successfully been carried out with 96 increments. A good practice is to acquire at least 128 increments for accurate prediction. A second concern is that LP not be extended too far (e.g., 128 points predicted to 4,096). W. F. Reynolds (2002) has found that, as a general rule, data presented in the phase-sensitive mode can be predicted fourfold (e.g., 256 data points can be predicted to 1,024), while absolute-value data can be extended twofold, 256 points to 512. A significant exception to the fourfold rule for phase-sensitive experiments concerns the H-detected, heteronuclear chemical-shift correlation experiments. In marked contrast to COSY and HMBC spectra, for which the interferograms are frequently composed of many signals, those of HMQC and HSQC spectra constitute only one (due to the directly attached C). LP s up to sixteen-fold can be performed in these experiments (Sections 7-8a and 7-8b). 

H decoupling for FLOCK typically is performed as the C signal is acquired and is accomplished with the WALTZ sequence (Section 5-8). FLOCK data are presented in either the phase-sensitive or the absolute-value mode. Because of uncertainty concerning both the location and intensity of correlations in FLOCK contour plots, cross sections should be taken through individual chemical shifts on both the H and C axes, as with HMBC spectra. 

Assignments are based on COSY, HOHAHA, DEPT, HETCOR, phase-sensitive NOESY, and HMBC experiments. 

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