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Bidysoxyletine Structure Elucidation

Bidysoxyletine

A new bicoumarin derivative, bidysoxyletine (1), was isolated from the leaves of Dysoxylum parasiticum (Osbeck) Kosterm by authors of [1].

1

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 [2], therefore the NMR spectroscopic data from [1] were used as input for ACD/Structure Elucidator (ACD/SE). The data are presented in Table 1.

Table 1. NMR spectroscopic data of compound 1.

C/X Label δC δC calc (HOSE) XHn δH M COSY H to C HMBC
C 1 116.200 118.860 C
C 2 109.800 111.340 CH 8.450 s 6.96 C 4, C 8, C 6, C 3
C 3 153.800 151.160 C
C 4 120.200 117.400 CH 6.960 s 8.45 C 9, C 2, C 6, C 3
C 5 129.400 131.700 C
C 6 143.600 142.900 C
C 7 157.700 159.440 C
C 8 125.900 129.850 C
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 11 136.800 137.840 C
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 15 130.900 131.690 C
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.

Figure 1.  Molecular connectivity diagram. Hybridizations of carbon atoms are marked by corresponding colors: sp2 – violet, sp3 – blue, not sp (sp2 or sp3) – light blue. Labels “ob” and “fb” are set to carbon atoms for which neighboring with heteroatom is either obligatory (ob) or forbidden (fb).

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.

Figure 2. IR spectrum of compound 1

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.

Figure 3. The six top ranked structures of the output file. Red arrows mark the non-standard COSY correlations.

We see that the first ranked structure (# 1) coincides with the structure of bidysoxyletine (1) determined in [1], 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 [1] using NMR, UV, IR, HR­ESITOFMS, and DDFT calculations was unambiguously identified by ACD/SE in 7 sec.

References

  1. 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
  2. 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

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