ACD/Structure Elucidator Suite Featured Solution

Aspterpenacid A

Sesterterpenoids are a relatively small group of terpenoids which have been found in the metabolites of terrestrial fungi, lichens, plant, insects, and various marine organisms including fungi, sponges, and coral. They always possess interesting carbon skeletons, including linear, monocyclic, polycyclic, and miscellaneous carbon portions, and exhibit diverse biological activities. In recent years, sesterterpenoids have attracted considerable attention due to their structural conciseness and diverse bioactivity.

Liu et al [1] carried out a chemical investigation of an endophytic fungus Aspergillus terreus H010, which was isolated from the mangrove plant Kandelia obovata. Two pentacarbocyclic sesterterpenoids, aspterpenacids A  and B , with an unusual 5/3/7/6/5 ring system, were isolated. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction analysis, and electronic circular dichroism calculations. The spectroscopic data used to elucidate the structure of aspterpenacid A (structure 1) was employed to challenge ACD/Structure Elucidator Suite.


1

Aspterpenacid A (1) was obtained as a colorless crystal. The molecular formula C27H42O5 was deduced on the basis of the HRESI TOF MS at m/z 445.2956 (calculated [M − H]

445.2954), indicating seven degrees of unsaturation. The IR data exhibited two carbonyl peaks (1679 cm−1 and 1716 cm−1) and a hydroxyl band at 3481 cm−1. The original NMR spectroscopic data from [1], which were utilized for structure elucidation by the Computer-Assisted Structure Elucidation (CASE) approach, are collected in Table 1. 

Click to expandTable 1. NMR spectroscopic data (in CDCl3) for Aspterpenacid A.

* 13C NMR spectrum prediction was performed using the HOSE code-based method [2].

Figure 1 shows the Molecular Connectivity Diagram (MCD) which was produced by Structure Elucidator Suite from the data in Table 1.


Figure 1. Molecular Connectivity Diagram (MCD) for Aspterpenacid A.

MCD overview. Two carbons (CH 83.70 and C 77, marked in light blue) are characterized by sp2 or sp3 hybridizations (not sp). A number of HMBC (green) and COSY (blue) connectivities are considered ambiguous, denoted by dotted lines. The latter arise due to presence of three pairs of C and H atoms in the respective 13C and 1H spectra, for which chemical shifts are identical (marked by underlined italic in Table 1).

However, no edits of MCD were made, and structure generation was initiated. As a result 37 structures were generated in 0.2 s. 13C chemical shift prediction was applied to all items of the output file using additive rules, neural networks and fragmental (HOSE code-based) approaches [2], and average chemical shift deviations (dI, dN and dA) calculated.  All 37 structures were then ranked in increasing order of dA values. The six top-ranked structures are presented in Figure 2.


Figure 2. The top-ranked structures generated for Aspterpenacid A by the software.

Figure 2 shows that the top-ranked structure #1 is identical to the structure of Aspterpenacid A (1) determined by the authors [1]. At the same time, we see that the difference between the dA deviations calculated for the first- and second-ranked structures is very small, and therefore the result obtained needs to be confirmed. In the original work [1], the structure of Aspterpenacid A was confirmed by X-ray crystallography. That structure, along with 13C chemical shifts assigned by Structure Elucidator Suite is shown below:


Figure 3: The structure for Aspterpenacid A with the 13C chemical shifts assigned by Structure Elucidator Suite.

Thus, structure of a new natural product containing an unusual ring system was determined in fully automatic fashion by ACD/Structure Elucidator Suite in 0.2 seconds.

A complete elucidation package that speeds up the elucidation process
and ensures that no candidate is overlooked.

References:

  1. Z. Liu,Y. Chen, S. Chen, Y. Liu, Y. Lu, D. Chen, Y. Lin, X. Huang, Z. She. (2016). Aspterpenacids A and B, Two Sesterterpenoids from a Mangrove Endophytic Fungus Aspergillus terreus H010. Org. Lett., 18:1406−1409.
  2. M.E. Elyashberg, A.J. Williams. (2015). Computer-based Structure Elucidation from Spectral Data (p. 454). Springer-Verlag Berlin, Heidelberg.

For more hands-on experience in the methods of Computer-Assisted Structure Elucidation, using ACD/Structure Elucidator, we recommend the textbook Computer–Based Structure Elucidation from Spectral Data from Springer, by M.E. Elyashberg and A.J. Williams. 

The special version of ACD/Structure Elucidator and 100 problems (in electronic format) which were discussed in the book are available at www.acdlabs.com/TeachingSE.