Structure elucidator CASE program

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. 

Chemical shift prediction. Computer-assisted structure elucidation, CASE programs. Alkaloids, Natural products. Structure elucidation... 

Computer-Assisted Structure Elucidation (CASE) is a paradigm that covers techniques and computer programs for the elucidation of structures with rule-based systems. 

CASE (computer-assisted structure elucidation) programs. ... 

Nuzillard and coworkers [44] also reported the application of the LSD CASE program to the elucidation of the structure of acosmine acetate (4) in 1999. The... 

Tab. 14.2 Impact of information content on the application of the COCON CASE program for the elucidation of the structure of oroidin (3).

ACD/Labs Structure Elucidator v7.0. In 42 min of computer time, the program output 296 structures that were sorted on the basis of the match between predicted shifts for each structure and the observed shift data. On this basis, the structure of quindoline, 6, was first in the output list with a deviation d=336 ppm. The next structure in the output list had a deviation of 5.26 ppm. Applications of the Structure Elucidator program to hundreds of examples have shown that only in rare cases does the actual structure have d>5 ppm. 

Fig. 8. HPLC trace of the J6-DMSO solution of a 2.5 mg sample of cryptospirolepine (7) stored for 10 years. None of the starting alkaloid remains in the sample (LC/MS data). The two largest degradant species, DP-1 and DP-2 (35 and 16%, respectively) have been identified. The former, DP-1, was quickly identified by both spectroscopist data interpretation and by the Structure Elucidator v7.0 CASE program as cryptolepinone. The structure of the latter, DP-2, ultimately identified as cryptoquindoline (8), was determined in parallel, both by a competent spectroscopist with extensive experience with this class of alkaloid structures and using Structure Elucidator v7.0.

Spectrum prediction is a frequently used technique during the structure elucidation process, but a detailed inspection of the results is necessary. Some programs offer the possibility to use different algorithms for spectrum prediction (usually HOSE code technology and neural networks). In such a situation both methods should be applied and the results obtained should be carefully compared [22]. At least in the case of different predictions a further critical evaluation of the result should be an obligation. 

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]. 

Pearlman DA, Case DA, Caldwell JW, Ross WR, Cheatham III TE, DeBolt S, Ferguson D, Seibel G, Kollman P (1995) AMBER, a computer program for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to elucidate the structures and energies of molecules. Comp Phys Commun 91 1—41... 

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