July 22, 2022
by Mikhail Elyashberg, Leading Researcher, ACD/Labs
A new bicoumarin derivative, bidysoxyletine (1), was isolated from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm by authors of .
The structure of 1 was elucidated by analyzing NMR, UV, IR and HR-ESI-TOF-MS spectra. DDFT calculations (B3LYP) were used to confirm the 13C NMR and UV spectroscopic data. The molecular formula of compound 1 was determined to be C36H40O6. Since the 13C NMR spectrum contained 18 signals, it was concluded that the molecule is symmetric, so each signal in this spectrum corresponds to resonances of two equivalent carbon atoms.
Structure elucidation of symmetric molecules is known to be challenging for CASE systems , therefore the NMR spectroscopic data from  were used as input for ACD/Structure Elucidator (ACD/SE). The data are presented in Table 1.
|C/X Label||δC||δC calc (HOSE)||XHn||δH||M||COSY||H to C HMBC|
|C 2||109.800||111.340||CH||8.450||s||6.96||C 4, C 8, C 6, C 3|
|C 4||120.200||117.400||CH||6.960||s||8.45||C 9, C 2, C 6, C 3|
|C 9||27.400||28.570||CH2||3.470||d||5.31||C 10, C 5, C 11, C 6|
|C 10||121.000||121.390||CH||5.310||t||3.47||C 17, C 9, C 12, C 5|
|C 12||39.000||39.840||CH2||2.020||t||2.08||C 17, C 13, C 10, C 14, C 11|
|C 13||26.100||26.700||CH2||2.080||q||2.02, 5.06||C 12, C 14, C 15, C 11|
|C 14||124.000||124.270||CH||5.060||t||2.08||C 18, C 16, C 12|
|C 16||25.500||25.760||CH3||1.600||s||C 18, C 14, C 15|
|C 17||16.000||16.170||CH3||1.740||s||C 12, C 10, C 11|
|C 18||17.600||17.710||CH3||1.540||s||C 16, C 14, C 15|
|O 1||OH||9.770||s||C 2, C 4, C 3|
The program automatically created the Molecular Connectivity Diagram (MCD). The slightly edited MCD is presented in Figure 1.
MCD overview. Carbon atoms C 109.8 and C 116.2 (light blue) are characterized by ambiguous hybridization (sp2 or sp3), and atoms C 157.70 have no HMBC correlations. These peculiarities usually lead to increasing the number of structures generated and longer processor time necessary for solving the problem. Therefore, it was desirable to introduce some additional structural information. As the IR spectrum clearly indicates the presence of carbonyl groups (strong band near 1700 cm-1 in Figure 2), the carbons C 157.7 were defined with the label “ob” (connection with a heteroatom is obligatory). This label was also set for atoms C 153.8 which have HMBC correlations to OH groups.
After the MCD checking for the presence of contradictions, the program reported about the presence of at least one nonstandard correlation (a correlation of the length which is longer that three chemical bonds) in the cumulative HMBC and COSY data. Consequently, Fuzzy Structure Generation (FSG) combined with fast 13C chemical shift prediction (about 30,000 shifts per second), using the incremental and neural network approaches and structural filtering was initiated. Results: k = 596 → (structural filtering) → 20 → (removal of duplicates) → 16, tg =7 sec. One COSY connectivity was extended during the structure generation.
Then 13C chemical shift prediction was performed using the HOSE code-based algorithm, and the output file was ranked in descending order of average deviations δA(13C) of the experimental chemical shifts from calculated ones. The six top ranked structures of the output file are shown in Figure 3.
We see that the first ranked structure (# 1) coincides with the structure of bidysoxyletine (1) determined in , and the small average and maximum deviations calculated for all kinds of spectrum prediction algorithms unambiguously point to this structure as the correct one. The structure with automatically assigned 13C chemical shifts is shown below.
Therefore a challenging symmetrical structure elucidated by the authors  using NMR, UV, IR, HRESITOFMS, and DDFT calculations was unambiguously identified by ACD/SE in 7 sec.
- F. F. Sofian, A. Subarna, T. Koseki, Y. Shiono. (2022). Structure elucidation of a new bicoumarin derivative from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm. Magn. Reason. Chem., 60(8), 857. https://doi.org/10.1002/mrc.5268
- M. Elyashberg, D. Argyropoulos. (2021). Computer Assisted Structure Elucidation (CASE): Current and future perspectives, Magn. Reson. Chem., 59(7), 669-690. https://doi.org/10.1002/mrc.5115