Enhanced automated structure elucidation by inclusion of two‐bond specific data

Abstract

The availability of cryogenically cooled probes permits routine acquisition of data from low sensitivity pulse sequences such as inadequate and 1,1-adequate. We demonstrate that the use of cryo-probe generated 1,1-adequate data in conjunction with HMBC dramatically improves computer-assisted structure elucidation (CASE) both in terms of speed and accuracy of structure generation. In this study data were obtained on two dissimilar natural products and subjected to CASE analysis with and without the incorporation of two-bond specific data. Dramatic improvements in both structure calculation times and structure candidates were observed by the inclusion of the two-bond specific data.

Determination of substitution sites in monosubstituted five‐membered aromatic heterocycles

“…Although we have demonstrated the application of 1,1-ADEQUATE on pyrrole derivatives only, extension of this approach to other heterocyclic compounds is obvious. The straightforward interpretation of 1,1-ADEQUATE data speaks again for their inclusion into computer-assisted structure elucidation (CASE) protocols as suggested by Cheatham et al [15] …”

Application of 1,n-ADEQUATE and Modified Variants to Structure Elucidation and Spectral Assignment Problems

“…22,38,55 For pairs of coupled protonated carbons correlated via 1 J CC couplings, the HSQC-1,n-ADEQUATE spectrum calculated using covariance methods will afford diagonally symmetric correlations observed at the carbon chemical shifts of the two coupled resonances. Correlations between adjacent protonated and nonprotonated carbons will lead to diagonally asymmetric correlations with the response observed at the F 1 chemical shift of the nonprotonated carbon and the F 2 chemical shift of the protonated carbon.…”

Primary Data Processing: Preparation, Input and Checking

“…This significantly simplifies structure generation, thereby reducing generation time and the number of generated structures. A comparison of structure elucidation with and without 1,1-ADEQUATE data has been published by Cheatham et al 12 The authors investigated the influence of a 1,1-ADEQUATE spectrum on the structure elucidation of retrorsine (Figure 8.23) as model example. 10,921 structures were generated in 70 min using a combination of COSY and HMBC correlations, and only eight structures were generated in less than 1 s using a combination of 1,1-ADEQUATE and HMBC data.…”

“…12 The MCD with information extracted from the COSY spectrum. Only the vicinal ( 3 J) connectivities are displayed.…”