August 1, 2017
by Mikhail Elyashberg, Leading Researcher, ACD/Labs
Abyssomicins are class I spirotetronate polyketides with a characteristic spirotetronate moiety. Abyssomicin C was the first reported inhibitor of the formation of p-aminobenzoate (p-ABA) from a natural source. Wang et al.  reported the discovery of 12 new analogs of abyssomicin as metabolites of the Streptomyces species. Amongst them Abyssomicin W (1) has an 8/6/6/6 tetracyclic core. Spectroscopic data of this compound were used to challenge ACD/Structure Elucidator Suite.
Compound 1 with a molecular formula of C20H26O8 confirmed by HR-MS has typical abyssomicin UV and NMR signatures with assumed structural differences at C-2, C-9, and C-16. Specifically, C-16 in 1 has both a unique 13C chemical shift (δC 171.5 ppm) and characteristic HMBC correlations with H-10 (δH 2.39 ppm) and H2-14 (δH 1.43, 2.45 ppm), consistent with a lack of C-2/C-16 bond and the presence of a novel lactone.
The NMR data from compound 1 taken from the literature are summarized in Table 1. These were entered into Structure Elucidator to automatically generate the Molecular Connectivity Diagram (MCD) shown in Figure 1.
|Label||dC||dC calc||XHn||dH||COSY||H to C
|C 5||46.1||36.41||CH2||1.54||3.26||C 3, C
6, C 7
|C 8||43.9||39.66||CH2||1.76||4.05||C 2, C
7, C 10
|C 1, C
2, C 15
|C 2, C
14, C 15, C 16
|C 11||71.7||70.9||CH||3.62||2.39||C 9, C
12, C 13
|C 14||40.6||35.94||CH2||1.43||2.44||C 15, C
16, C 20
|C 17||17.2||19.26||CH3||1.04||3.26||C 3, C
4, C 5
|C 18||28||27.15||CH3||1.16||C 6, C
|C 19||19||19.3||CH3||1.28||C 11, C
12, C 13
|C 20||16||15.67||CH3||0.93||2.44||C 12|
|O 2||OH||5.68||C 5, C
6, C 7
|O 3||OH||6.11||C 10, C
Figure 1. Abyssomicin W. Molecular Connectivity Diagram generated automatically from the data in Table 1. No manual edits were needed. The green arrows represent a max. 3 bond connectivity (HMBC data) and the blue arrows a max. 1 bond connectivity (COSY data).
No edits of MCD were made. Discrete Structure generation was initiated using the software default parameters. Structure generation gave the following result: k→1424→41→41, tg = 1.4 s
The six top ranked generated structures are shown in Figure 2. The structures are ranked according to lowest mean deviation of experimental from HOSE-codes predicted 13C chemical shift difference.
Figure 2. Abyssomicin W. Six top ranked structures of the output file.
Structure #1 coincides with the structure of Abyssomicin already reported .
As the difference between deviations calculated for structures 1 and 2 is small some further confirmation is needed. This could be achieved by either additional NMR data (NOESY/ROESY or additional HMBCs at different coupling constant settings) or by DFT-based chemical shift prediction [2,3].
- X. Wang, S. I. Elshahawi,W. Cai,Y. Zhang, L. V. Ponomareva, X. Chen, G. C. Copley, J. C. Hower, C.-G. Zhan, S. Parkin, J. Rohr, S.G. Van Lanen, K. A. Shaaban, J. S. Thorson. (2017). Bi- and Tetracyclic Spirotetronates from the Coal Mine Fire Isolate Streptomyces sp. LC-6-2. J. Nat. Prod., 80: 1141−1149.
- M.E. Elyashberg, A.J. Williams. (2015). Computer-based Structure Elucidation from Spectral Data (p. 454). Springer-Verlag Berlin, Heidelberg.
- A. V. Buevich, M. E. Elyashberg. (2016). Synergistic combination of CASE algorithms and DFT chemical shift predictions: a powerful approach for structure elucidation, verification and revision. J. Nat. Prod., 79 (12): 3105–3116.