1,«-ADEQUATE data

Using 1,1-ADEQUATE Data in Conjunction with CASE... 

Another alternative for the interpretation of 1,1-ADEQUATE data is available by overlaying HSQC and 1,1-ADEQUATE spectra. By plotting the two spectra in different colours, as was done in Figure 4, the direct 1H/13C heteronuclear correlation response is visible and provides a guide for interpretation that is sometimes convenient. A further alternative would be to overlay 1,1-ADEQUATE and GHMBC spectra responses appearing in both are identified as 2/ch correlations and all remaining... 

In 2007, Stadlbauer and co-workers66 reported the use of 1,1-ADEQUATE data to identify quaternary carbons located two-bonds from various protons in the structure of a quinolinylpyrido[3,2,l-/k]carbazolone (17). For the acquisition of the 1,1-ADEQUATE data, the authors used a very large 200 mg sample of 17 but did not give details of the optimization, digitization, or acquisition time for the experiment. 1,1-ADEQUATE correlations observed are shown on the structure. 

ADEQUATE data. For data set A, the program generated 1310 structures when hybridization states were not pre-defined. In contrast, data sets B, C, and D led to the generation of 27, 16, and 4 structures, respectively. Complete 1,1-ADEQUATE correlations reported for the bromo- and dibromophakellins (18a, 18b) and the bromo- and dibromoi-sophakellins (19a, 19b) are shown on the structures. 

As a part of a further investigation of the impact of 1,1-ADEQUATE data on CASE programs, Cheatham and co-workers46 employed retrorsine (22) and delcosine (23) as model compounds. HMBC and 1,1-ADEQUATE data were acquired for 22 and a suite of HMBC, H2BC, and 1,1-ADEQUATE spectra were acquired for 23. Usefully, the authors also reported details of their efforts to optimize the acquisition of the 1,1-ADEQUATE data used as input for the CASE investigation. Strychnine (1) was used by the authors to explore the optimization of experimental conditions. Using a 600-MHz instrument equipped with a 5-mm cryoprobe, the authors compared s/n for various 1,1-ADEQUATE correlations of strychnine using 10 mg samples in 5 mm tubes, and both 5 and 2.5 mg samples in 3 mm tubes. Acquisition times of 15 h were used for these measurements. 

The authors work demonstrated that even samples as small as 2.5 mg could be studied yielding data with s/n > 5 1. They further demonstrated for samples with aromatic rings that 60 Hz optimization of the experiment was beneficial and that correlations to aliphatic carbons with smaller LJcc couplings did not experience a serious adverse impact due to the larger optimization but the reverse was not true. Correlations to aromatic carbons were not amenable to optimization biased toward aliphatic carbons (e.g. 40 Hz). Correlations observed in the 1,1-ADEQUATE spectrum of retrorsine (22) are shown on the structure. Complete 1,1-ADEQUATE correlations were not shown for delcosine (23) but the authors noted that the key correlations shown on the structure that were observed in the 1,1-ADEQUATE data were not observed in the H2BC spectrum acquired. The impact of the availability of the 1,1-ADEQUATE data on the Structure Elucidator CASE program is discussed in Section 7. 

USING 1,1-ADEQUATE DATA IN CONJUNCTION WITH CASE METHODS... 

To date, there have been four reports published that have examined the impact of 1,1-ADEQUATE correlation data on structure generation times and the number of structures generated for various CASE programs.46 47 53 55 The first of the studies discussed above used limited 1,1-ADEQUATE data in a COCON computation rim for the relatively simple molecule 4,5-dibromopyrrol-2-carboxylic acid (4).53 In the same report, the authors considered the effect of 1,1-ADEQUATE correlations that would theoretically be expected for manzacidin A (5), however no 1,1-ADEQUATE data were actually acquired. The results for 4 and 5 are summarized in Table 2. 

The most recent report of Myer and Kock47 afforded a more robust assessment of the value of 1,1-ADEQUATE data as a part of the input data set for the COCON CASE program. The output of the structure generation for the brominated phakellins (18a, b) and brominated isophakellin (19a, b) alkaloids is summarized in Table 3. Structures generated without specified hybridization are noted on the first line for each compound that can be compared with the number of structures generated when pre-defined hybridization was employed on the second line for each... 

HSQC-14-ADEQUATE spectra. When 1,1-ADEQUATE data are to be utilized in conjunction with UIC or GIC co-processing, acquisition times and/or sample sizes may be reduced. In the former case, with an 10 mg sample of strychnine (1), acquisition times could be reduced to approximately 4 h while still giving very usable HSQC-1,1-ADEQUATE spectra. Using the latter tact, the authors demonstrated that it was possible to reduce the sample size to <0.5 mg of 1 over a weekend when the data were acquired using a 600-MHz 1.7 mm Micro CryoProbe.50 Clearly, for applications such as this, there appears to be considerable potential for the utilization of UIC or GIC co-processing of multiplicity-edited GHSQC and 1,1-ADEQUATE spectra. 

In the same sense that multiplicity-edited GHSQC and 1,1-ADEQUATE 2D NMR spectra can be combined using either UIC83 84 or GIC,52/95 the same can also be done with 1, -ADEQUATE data. Thus, the HSQC-l,n-ADEQUATE spectrum of strychnine (1) is shown in Figure 22. 

Elyashberg applied ACD/Structure Elucidator to the problem using the HMBC, COSY, HMBC, and 1,1-ADEQUATE data as inputs. A number of... 

The reader interested in the appHcation of 1,1 - and 1, -ADEQUATE in the elucidation of the structures of the phakellin and isophakellin alkaloids can find a discussion of that aspect of the structure elucidation either in the Meyer and Kdck [91] manuscript or the topic is also extensively discussed in the 2011 review of the use of 1,1- and 1, -ADEQUATE data in structure elucidation by Martin [92], 1,1-ADEQUATE data, in particular, can be quite useful in estabhshing the adjacency of pairs of protonated carbons or protonated carbons and adjacent quaternary carbons. 1, n-ADEQUATE data are complimentary to EIMBC data in that the most prevalent correlation observed in a 1, -ADEQUATE spectrum is via Jcc> which is equivalent to a cH correlation in an HMBC spectrum. The interested reader should also be aware of an experiment known as dual-optimized inverted Jcc 1adequate that affords both Jcc and "Jcc correlations in a single experiment, the former correlations are inverted while the latter group has positive phase [93]. 

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