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Structure Elucidator Suite 23rd Anniversary Promotion

Structure Elucidator Suite Anniversary Promotion

Take Advantage of the Structure Elucidator Suite Promotion Today!

We are celebrating our 23rd year of our elucidation software with a matching 23% discount on ACD/Structure Elucidator Suite until August 23, 2021. Read on below to learn more about the software and claim this limited time offer.

What ACD/Structure Elucidator Suite Does for You

Solve structures quickly & confidently

Potential structures are generated quickly and then are quantitatively ranked by multiple methodologies.

Avoid unnecessary elucidations

Dereplication using internal and/or external databases (including PubChem and ChemSpider) is performed before you spend time solving the structure.

Use for all your structures

From small designer molecules to large natural products, Structure Elucidator has been proven to work for a variety of compound sizes and complexities.

Don't fret over imperfect data

Structure Elucidator is equipped to handle many challenges including small impurities, unresolved peaks, non-standard correlations, and more.

Go beyond the 2D structure

Determine relative stereochemistry and elucidate stereoisomers from a flat 2D structure using NOESY/ROESY spectra.

Integrate with all analytical data

With ACD/Structure Elucidator Suite, you get access to all the advanced processing and interpretive features and algorithms of ACD/NMR Workbook Suite and ACD/MS Workbook Suite. This includes vendor agnostic data processing for NMR, MS, UV-Vis, FT-IR, and chromatography techniques.

You Can Be Confident in Structure Elucidator Suite

>1000
structures solved

100s
of peer-reviewed publications

100%
success rate in the Structure Elucidator Suite Challenge

With more than 1000 structures solved and a few hundred peer-reviewed publications, Structure Elucidator is the most peer-reviewed CASE software on the market.

We want everyone to be as confident in Structure Elucidator as we are. Since 2013, we have allowed anyone to bring Structure Elucidator their most challenging data sets in the Structure Elucidator Suite Challenge. To date, Structure Elucidator has correctly solved all 82 challenges issued!

Symmetric Helical Synthesis Product

This month's problem is again a bit different from the others. It comes from the Department of Chemistry, University of Bath, UK. John Lowe had been trying to challenge Structure Elucidator and asked his colleagues at the Department for interesting problems. David Carbery gave him two synthetic samples, A and B, that had been prepared by his group for some other physicochemical studies and were thought to be impossible to elucidate by NMR [1].

The samples were isomeric, with a MW of 582.2042 and a molecular formula C38H30O6. The structures were symmetric so exactly half the signals were visible by NMR, i.e. 19 carbons. The actual spectra of A and B were different, which verified that it was two different compounds. However, the differences were only in the positions of the peaks, not in the number of signals and correlations observed. The differences were also quite small in some cases.

A series of NMR spectra were recorded for these samples, including a 1D 1H, 1D 13C, COSY, HSQC and HMBC. Already from the COSY experiment it was clear that there was something else strange: There were peaks at 6.79 ppm (dt), 7.06 ppm (td), 7.14 ppm (tt), 7.3 ppm (td) and 7.25 ppm (dt) that were coupled in the order listed, so all 5 of them formed a coupling network. These are undoubtedly all aromatic protons, but we could not think of a way that an aromatic ring or rings could have 5 non-equivalent protons.

The 1D 13C spectrum also had some very closely spaced peaks: 3 signals within 0.1 ppm at the 130.7 ppm region and another 2 within 0.06 ppm in the 127.9 ppm region. (Figure 1).

Symmetric Helical Synthesis Product
Figure 1: The regions around 130.7 and 127.9 ppm of the 1D 13C spectrum of compound A.

With such close proximity the default resolution of any 2D spectrum is not sufficient to resolve any observed correlations. This would have normally not been a problem, however in this case together with the symmetry of the molecule the difficulty of coming to a solution was increased. Structure Elucidator would need to examine every possibility for the correlations and generate multiple MCDs internally, which would increase the elucidation time. To try to resolve this problem, band-selective versions of the experiments (HMBC) were recorded, focusing on the region of 120-140 ppm in F1. Band-selective experiments use variations of the standard pulse sequences with selective instead of hard RF pulses, allowing the selective observation of a region of the spectrum. They are similar to the standard experiments in terms of acquisition time and sensitivity but since they record the same number of increments for a much narrower spectral window in F1 the resolution can be increased quite a bit. Band selective experiments are very easy to setup with modern NMR instruments and chemists should not be hesitant to use them. The result, in comparison with a conventional HMBC, is shown in Figure 2. The use of these experiments allowed the full resolution of the ambiguities and thus no dotted lines were present in the MCD.

Symmetric Helical Synthesis Product
Figure 2: Conventional (left) and band-selective (right) HMBC spectrum of compound A in the region 7.0-8.0 ppm in F2 and 129.8-131.6 ppm in F1. The acquisition time for both the spectra was approximately the same, just under 60 minutes on a 500 MHz system with a standard, non-cryogenically cooled probe.

Since the compounds are slightly proton deficient and because of their symmetry, the HMBC spectra were recorded twice, optimized for two coupling constants: 8 Hz and 5 Hz. This allowed a few more correlations to be observed.

The NMR data collected for compound A are shown in Table 1. To accommodate for the symmetry of the problem the table of 13C data was edited and each signal was set to correspond to 2 carbons. The resulting MCD is shown in Figure 3.

Table 1: The NMR data extracted from the spectra and used in ACD/Structure Elucidator. Each line corresponds to 2 carbons, because of the problem symmetry.

Symmetric Helical Synthesis Product
Symmetric Helical Synthesis Product
Figure 3: The MCD generated by the program, after the edits described in the text.

There are 38 carbon atoms shown in the MCD, in accordance with the MF. There are 4 sp3 and 4 sp2 atoms that have been labelled with "ob", meaning that they must be connected to a heteroatom. The 4 sp3 ones were set like that automatically while the 4 sp2 ones manually, as they are at a chemical shift range typical for carbonyls. There are two sp3 carbons that are labelled "fb" meaning that they cannot be connected to a heteroatom. There are also 6 oxygen atoms that are "floating", meaning that there is no evidence as to where they are bonded. We also see that some of the correlations are marked as green while others are magenta. This indicates the estimated length of the correlation: green ones are up to 3 bonds and magenta ones up to 4 bonds long. This is derived mostly by the intensity of the HMBC peaks and, when in doubt, it is set to up to 4 bonds.

There were some edits done to the MCD: The bonds between the methyl signal and the CH group were manually set as they are very clearly present based on the HSQC and COSY spectra. The hybridizations of all the other carbon signals above 119 ppm was set to be sp2 as it was certain that there are no sp carbons in the product.

Before starting the generation and since we had very high resolution HMBC spectra, the tolerance for the 13C shifts was set to 0.001 ppm instead of the default 0.0076. This helps to accelerate the elucidation as the position of each carbon signal is not allowed to vary as much.

The MCD passed all tests, no contradictions were found and no edits were made. After this strict structure generation [2,3] was initiated with the following results: k = 2449 → (spectral filtering) → 113 → (removing duplicates) → 113,  tg = 1 h 46 m 26 s.

The top 3 structures generated are shown in Figure 4.

Symmetric Helical Synthesis Product
Figure 4: The top 3 structures generated by the program.

We can see that first two structures are very closely related, with the one derived from the other by "breaking" the middle aromatic ring, rotating one half, and re-forming the ring. We see that the average deviations between the predicted and experimental chemical shifts using the three methods built into SE are very close, however the maximum deviations observed for the third structure are almost double that for the other two. This, together with the highly unusual 10-membered bridged ring with double bonds effectively rules it out.

The correct structure is clearly one of the two first ones. We see that there is no clear "winner" based on the mean deviations between observed and calculated chemical shifts: Using the HOSE codes approach the first structure is correct, however using the neural networks approach the second one is better. Moreover, there is no bond correlation experiment that could have hinted at the correct one. Additionally, observing the structures more carefully, we can see the reason why we had the 5 non-equivalent, coupled aromatic protons: The mono-substituted aromatic ring is, in both cases, in a very sterically hindered environment and it is unlikely that it can rotate freely, which would have made some of its protons equivalent. So, the non-equivalency observed is because of stereochemistry reasons.

Similar results are obtained if we analyse the data for compound B. The same two structures are generated and ranked at the top, which means that the synthesis produced both isomers which were later separated and analysed. In order to solve this final problem a 2D-NOESY spectrum was recorded. This spectrum for compound B is shown in Figure 5.

Symmetric Helical Synthesis Product
Figure 5: Expansion of the 2D-NOESY spectrum region for compound B, showing the correlations between the methyl of the ester group with the aromatic protons of the monosubstituted ring.

It is clearly seen that for the case of compound B, NOESY correlations between the methyl protons of the ester group and some of the protons of the monosubstituted ring are observed, indicating that these are close in space (ca. <5 Å). No such correlations are observed for compound A. This clearly proves that the correct structure for compound A is the first one in Figure 4, while for compound B it is the second one. It also provides a direct proof of the steric hindrance in the rotation of the monosubstituted ring: Only correlations to 3 of the 5 protons are observed, the ones that are the closest. If there was free rotation possible then correlations to all the protons would have been seen.

The final structures of compounds A and B are shown in Figure 6, together with the assigned 13C chemical shifts.

Symmetric Helical Synthesis Product
Figure 6: Elucidated structures and observed 13C chemical shifts for compounds A (left) and B (right).

In conclusion Structure Elucidator was able to solve the structures of two helical, symmetric synthetic compounds with some quite unique challenges, in a relatively short time.

References:

  1. Carbery, D. R.; Lowe, J. P.; Moser, A.; Argyropoulos, D., "Computer Assisted Structure Elucidation of Two Isometic, Highly Symmetrical Helical Molecules". In EUROMAR Aarhus, Denmark, 2016.
  2. M. E. Elyashberg, A. J. Williams, Computer-based Structure Elucidation from Spectral Data. The Art of Solving Problems, Springer, Heidelberg, 2015.
  3. M. Elyashberg, D. Argyropoulos, in eMagRes, Vol. 8 (Eds.: R. K. Harris, R. L. Wasylishen), Wiley, 2019, pp. 239.

Synthetic product, C14H13N3O

This month's elucidation is a bit different. We will see the case of an unexpected synthetic product coming from Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) in Berlin, from the lab of Dr. Marc Nazaré. The dataset was provided to ACD/Labs as part of our Structure Elucidation Suite Challenge1 by Dr. Peter Schmieder. Dr. Rana Alsalim, Dr. Peter Lindemann and Dr. Edgar Specker also worked on this project.

The product was isolated after a reaction and it was found by HR-MS to have a molecular formula of C14H13N3O. Even though it is a rather small molecule it presented some quite interesting challenges.

To begin with, the spectra indicated that the sample was not particularly clean. In the 1D 1H spectrum shown in Figure 1 we can see that apart from the well-defined peaks in the aromatic region there is a broad group of peaks at around 3.8 ppm and several smaller peaks below 2.5 ppm. Quite a few of the peaks are known common impurities, like the peaks at 0.8 ppm and 1.29 ppm that probably appear because of the lubricating grease that was used on the ground glass joints of the glassware, but several others are really unknown. Interestingly the areas where peaks are, appear to be sitting on top of broad features of the spectrum, indicating a variety of similarly structured compounds. The fact that the TMS line appears nice and sharp eliminates the possibility of an instrumental problem (e.g. mis-set high order shims). Fortunately the situation is much clearer in the 13C spectrum (Figure 2) where only a little bit of "chemical noise" is observed and in all cases the intensities are much lower than the intensities of the real sample peaks.

Synthetic product C14H13N3O
Figure 1: The 1D 1H spectrum of the compound. The peak-picking and integration have been done after the HMQC spectrum was analysed.
Synthetic product C14H13N3O
Figure 2: The 1D 13C spectrum of the compound. The 14 strongest peaks have been picked.

The 1D 13C spectrum has 14 signals, which corresponds exactly to the number of carbons in the supplied MF. We will be using this to help us identify which are the proper peaks to select in all the other spectra.

Before proceeding to the actual elucidation it is a good idea to see if there is any known compound that has a similar carbon spectrum. This step is generally referred to as "dereplication"—if something known exists with a similar spectrum then one can avoid spending time doing the whole elucidation again, replicating what is already known. Structure Elucidator comes with a database of ca. 98 million predicted 13C spectra for all the structures of the compounds found in PubChem. This database is fully searchable by the peaks observed in the 13C spectra (1D and 2D HSQC, HMBC). The molecular weight and molecular formula can also be used, if known, to facilitate the search.

A search of this database for something similar to the product we had gave, in essence, no results. If one does a strict search (i.e. all the peaks visible are true peaks and not impurities, and none is missing or extra) then there is nothing found. If the criteria about the excess or lack of peaks are relaxed then some structures start appearing but it is evident that they are not correct. Some results from this search are shown in Figure 3. The only fact that is verified is that there are at least two aromatic rings in this structure. This is a bit surprising because one would have thought that such a small molecule would have been known. Apparently this is not the case, so we proceed with the complete elucidation.

Synthetic product C14H13N3O
Figure 3: A couple of the structures that were found by the program to have similar 13C spectra, with up to 2 missing or extra peaks. Even though it is clear that they are not correct (the left one has 2 methyl groups, the right one has a methylene and no methyl group) the result indicates that we probably have two aromatic rings and a nitrile group.

The next step is to analyse the 1H-{13C} HMQC spectrum (Figure 4). Since we know where the 13C signals are we can focus on these frequencies only, thus avoid accidentally selecting erroneous peaks. We can identify 8 peaks in the HMQC spectrum which when correlated to the 1D 1H spectrum show us that we have 7 aromatic protons, all of them CH's, and one singlet peak at 3.8 ppm which appears to be a methyl, after looking at the integration.

Synthetic product C14H13N3O
Figure 4: The 1H-{13C} HMQC spectrum

The 1H-{13C} HMBC spectrum (Figure 5) is analysed in the same way, only picking the peaks that have been identified so far as being legitimate sample peaks, both on the 1D 13C and the 1D 1H spectra. In the case of this spectrum there are several more erroneous peaks that appear. Some of them are because of the single bond artefacts that are very common in HMBCs and some other because of the impurities. ACD/Labs software has algorithms built-in and will automatically avoid picking single bond peaks in HMBC spectra. The general strategy here is to only pick the peaks that one is certain about and avoid over-picking and thus constraining the problem without a reason.

Synthetic product C14H13N3O
Figure 5: The 1H-{13C} HMBC spectrum

A 2D-COSY spectrum was also supplied (not shown) that helps identify the coupling networks of the aromatic protons and safely establish that we have two aromatic rings in the structure. The full list of spectral data obtained by these spectra is shown in Table 1, automatically generated by Structure Elucidator.

Table 1. Table of Spectral Data for the spectra analysed. [+]

Together with Table 1, SE generated the Molecular Connectivity Diagram shown in Figure 6.

Synthetic product C14H13N3O
Figure 6: The automatically generated MCD. Manual edits, as described in the text, are underlined.

Carbon atom hybridization was defined by the program automatically. There were only 3 edits made, these being for carbon 12 (144.94 ppm), carbon 13 (149.29 ppm) and carbon 14 (153.98 ppm) who were set to be of sp2 hybridization. There were two carbons coloured light blue (C3 at 99.4 ppm and C4 at 106.79 ppm), meaning that these could not be of sp hybridization and 3 carbon atoms coloured black (C2 at 97.06 ppm, C7 at 117.97 ppm and C8 at 119.57 ppm) meaning that they were of unknown hybridization. Also carbon C1, at 55.51 ppm, was labelled with "ob" meaning that it must be connected to a heteroatom. The HMBC correlations were set as either green (2 -3 bonds) or magenta (4 bonds), depending on their intensity on the spectrum. This was also done automatically by the program. If this appears to be causing problems then Fuzzy Structure Generation can be activated.

The MCD was checked for contradictions and it passed with only a warning, that there were more 1H atoms in the MF than detected in the spectra. This is usually an indication that there are some exchangeable protons (e.g. -OH or –NH groups) that are not visible, and it is not a problem for SE. After the test, common mode generation was initiated by also selecting the option to allow bonds between heteroatoms and to allow bonds between heteroatoms of the same kind, since one of the precursor molecules had a diazonium group. The results were: k = 660474 → (filtering) → 10 → (removing duplicates) → 7, tg = 13m 15s.

The results were ranked by the average deviation between experimental and predicted 13C chemical shifts. In the previous Elucidations of the Month we have been ranking the results using 13C chemical shifts predicted with the HOSE codes approach. This time we used both the HOSE codes method and artificial neural networks. The top 3 structures, ranked in increasing average deviation using the neural networks approach, are shown in Figure 7.

Synthetic product C14H13N3O
Figure 7: The top 3 structures generated

We see that the difference in the average deviation between the first and the second structure is very small. Using the neural networks approach the first structure has an average deviation, dN(13C), of 2.743 ppm and the second 2.771 ppm. Using the HOSE codes approach the first structure has an average deviation, dA(13C), of 2.901 ppm and the second 2.669 ppm. So the first structure is better using the neural networks approach and the second using the HOSE codes. In general average deviations below 3.5 ppm are acceptable, so both the structures are plausible. However the difference in the average deviations is very small and it is not possible to make a safe decision on which one is the correct one. The fact that the two prediction methods give the opposite result is further proof that there is a clear ambiguity in the sorting of the generated structures. One could use here some information from the synthesis of this compound and declare the first structure as the correct one, however since this was a completely unexpected result such an assumption would be dangerous.

It has been shown2-3 that in such cases DFT based chemical shift prediction allows for resolving this ambiguity and selecting the correct structure. However, DFT calculations may not always be an option for some groups, while recording additional NMR spectra is far easier. Since the MF contains nitrogen atoms a 1H-{15N} HMBC was the experiment chosen to be run in addition. This spectrum is shown in Figure 8.

Synthetic product C14H13N3O
Figure 8: The 1H-{15N} HMBC spectrum.

It is clear that only two of the three nitrogen atoms have been identified in this spectrum. This is not a problem as SE can solve problems under the conditions when some skeletal atoms have no 2D NMR correlations ("floating atoms"). In fact the MCD shown in Figure 4 already has 3 "floating" nitrogen atoms. We also see that most of the correlations appear to already identified proton signals, confirming their validity. There are two peaks for the nitrogen signal at 79 ppm not correlating to any proton signal, however they appear to be symmetric to a broad proton signal at ca. 6.14 ppm. These peaks are the single bond artefact and the fact that they appear around the broad peak at 6.14 ppm indicate that we have an –NH group.

The rest of the peaks appear to be of similar intensity except of the peak at 6.36 ppm in proton and 79.08 ppm in 15N, which is significantly weaker. While all the other peaks were set as corresponding to a 2-3 bond distance this particular one was set by the program as a 4 bond distance. The new MCD is shown in Figure 9. We see now that there are lines correlating two of the nitrogen atoms to carbons.

Synthetic product C14H13N3O
Figure 9: The automatically generated MCD using the 15N correlation data

Common mode structure generation was initiated again and the results were: k = 1800 → (filtering) → 2 → (removing duplicates) → 2, tg = 17s. The two structures generated are shown in Figure 10.

Synthetic product C14H13N3O
Figure 10: The two structures generated after the MCD was enriched with 1H-15N HMBC data

We now see that only the first structure generated before was generated again, thus the ambiguity that existed has been removed. We also see that the second structure generated has much higher average deviations between the experimental and the predicted chemical shifts, leaving no doubt about the validity of structure 1. We also saw a very spectacular 46x improvement in the structure generation speed.

The generated structure was found to be in agreement with what the FMP Berlin group had in mind and had already determined independently. The full structure together will all the chemical shifts assigned is shown in Figure 11.

Synthetic product C14H13N3O
Figure 11: The structure of the synthetic product, together with the 1H, 13C and 15N chemical shifts of the atoms.

The above illustrate the case where additional NMR spectra can not only help in removing ambiguities but also in decreasing the analysis time. Even though DFT calculations are an appealing and maybe easy way out from such situations, sometimes just recording an additional spectrum can have a really determining effect. 1H-15N HMBC spectra are easy to perform with the instruments available these days and should not be considered exotic and only for the experts. The same is true for several other advanced NMR experiments.

References:

  1. ACD/Labs Structure Elucidation Challenge
  2. 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.
  3. A.V. Buevich, M. E. Elyashberg. (2018). Towards unbiased and more versatile NMR-based structure elucidation: A powerful combination of CASE algorithms and DFT calculations. Magn. Reson. Chem., 56: 493–504. DOI: 10.1002/mrc.4645

Chloraserrtone A

Chloranthus serratus (Chloranthaceae) can be found throughout southern China. It has been used as a traditional Chinese medicine. The characteristic secondary metabolites of the genus Chloranthus are sesquiterpenoids, especially the sesquiterpenoid dimers. These exhibit a wide range of bioactivity. About 70 lindenane-type sesquiterpenoid dimers have been isolated from this genus over the past three decades.

Chloranthus, and most of the sesquiterpenoid dimers are biosynthesized from two lindenane-type sesquiterpenoid monomers connected via a six-membered ring (C-4−C-15−C-9′−C-8′−C-6−C-5) by an endo Diels−Alder cycloaddition reaction.

Compounds with new skeletons are constantly being isolated from this genus, and the structural diversity of sesquiterpenoid dimers has attracted the attention of an increasing number of researchers.

Chloraserrtone A (1), a new sesquiterpenoid dimer with two lindenane-type sesquiterpenoid monomers bridged by two six-membered rings, was isolated from Chloranthus serratus by Bai et al [1]. A combination of UV, IR, NMR, HRESIMS, and X-ray diffraction data were used to elucidate the structure of 1. Compound 1 represents the first lindenane-type sesquiterpenoid dimer with an extremely unique skeleton.

Chloraserrtone A
1

Chloraserrtone A was obtained as colorless crystals with a specific rotation of [α]D 20 −39 (c 0.2, CH2Cl2) [UV (MeOH) λmax (log ε) 266 (3.55), 204 (3.73) nm]. The molecular formula of 1 was established as C32H36O9 by the HRESIMS ion at m/z 587.2243 [M + Na]+ (calcd 587.2252), implying 15 indices of hydrogen deficiency. IR absorption bands at 3352, 1730, and 1636 cm−1 suggested the presence of hydroxy, carbonyl, and olefinic groups.

The molecular formula of 1 and the NMR spectroscopic data tabulated in [1] were entered into ACD/Structure Elucidator (Table 1).

Table 1. NMR spectroscopic data of Chloraserrtone A. [+]

The automatically generated Molecular Connectivity Diagram (MCD), which displays all atoms along with their properties and HMBC and COSY connectivities, is shown in Figure 1.

Chloraserrtone A: Molecular connectivity diagram
Figure 1. Molecular connectivity diagram.

MCD overview. Atom properties (hybridization and possibility to be connected to a heteroatom) were set by the program automatically based on the system knowledge base. Four carbon atoms, (C 81.1, C 84.4, C 125.4 and C 127.7) colored in light blue, are assigned ambiguous hybridization "not sp" (sp2 or sp3). No manual edits were made on the MCD.

After checking the MCD for the presence of contradictions the program informed us that  "The minimum number of non-standard connectivities (NSCs)  is 1", and the carbon atom CH3 17.50 was indicated  as  a potential origin of a NSC. Therefore Fuzzy Structure Generation (FSG) was enabled with the options automatically determined by the program. Results: k = 77,606 (spectral and structural filtering) → 10 (removal of duplicates) → 6,  tg = 2 m 25 s.

13C and 1H NMR chemical shift prediction was carried out for the structural output file  using three empirical methods common for ADC/SE (HOSE code based, neural networks, incremental approach), and the structures were ranked in increasing order of average  deviation dA(13C) between experimental  and calculated chemical shifts. The three top ranked structures are presented in Figure 2.

Chloraserrtone A: The top 3 structures of the output file ranked in increased order of average deviation
Figure 2. The top 3 structures of the output file ranked in increased order of average deviation dA(13C). Designations: dA(13C)—average deviation between experimental and predicted chemical shifts using the HOSE code approach; dN(13C)—as before but using the artificial neural networks predictions approach; dI(13C)—as before but using the Incremental prediction approach.

We see that all three methods of NMR chemical shift prediction pointed to structure #1 as the best one. Comparison of this structure with structure of chloraserrtone A determined by authors [1] and confirmed by X ray analysis shows that they are identical.

Thus, the structure of an unusual new natural product whose molecule contains 8 fused rings was elucidated by ACD/Structure Elucidator fully automatically in 2.5 min.  The elucidated structure together with the 13C chemical shifts which were  assigned by the program is shown below. A red arrow directed from CH3 17.50 to C 198.90 denotes a long-range HMBC correlations of four chemical bonds length. This is the atom that was selected by the program as the potential origin of the NSC, after the analysis of the MCD.

Chloraserrtone A

References:

  1. B. Bai, S.-X. Ye, D.-P. Yang, L.-P. Zhu, G.-H. Tang, Y.-Y. Chen, G. Q. Li, Z.-M. Zhao. (2019). Chloraserrtone A, a Sesquiterpenoid Dimer from Chloranthus serratus. J. Nat. Prod., 82: 407−411.

How Structure Elucidator Suite Works

Structure Elucidator Suite Workflow
Structure Elucidator Suite Workflow Step 1
  1. Import raw or processed analytical data, including at least 1D 1H, HSQC, HMBC. Other spectra such as 1D 13C, COSY, HSQC, and other heteronuclear correlation experiments can always help.
Structure Elucidator Suite Workflow Step 2
  1. Dereplication is performed using internal and external databases, including PubChem and ChemSpider. This helps to ensure a compound hasn’t already been identified before proceeding with the elucidation.
Structure Elucidator Suite Workflow Step 3
  1. Peak-pick the real peaks in your spectra. ACD/Labs NMRSync functionality that is included in Structure Elucidator Suite automatically synchronizes peak picking and assignment across all spectra for a particular dataset.
Structure Elucidator Suite Workflow Step 4
  1. The molecular connectivity diagram (MCD) is generated from the spectral data.
Structure Elucidator Suite Workflow Step 5
  1. Input the molecular formula, as determined in most cases by HRMS. This will add any atoms to the MCD that were not generated from the spectral data.
Structure Elucidator Suite Workflow Step 6
  1. Structure generation of all possible constitutional isomers from MCD can be done by Strict or Fuzzy algorithms depending on the amount of ambiguity in the spectral data.
Structure Elucidator Suite Workflow Step 7
  1. Structures are ranked quantitatively based on chemical shift deviations from predicted spectra by three different methodologies: method of increments, fragmental approach (based in HOSE codes), and artificial neural networks.
Structure Elucidator Suite Workflow Step 8
  1. If desired, stereoisomers can be elucidated at this point with the inclusion of NOESY/ROESY spectra.

Structure Elucidator Is Continuously Improving

Scroll through the history of Structure Elucidator to learn about all the improvements and innovations we have implemented over 23 years!

1968: First CASE system proposed

Mikhail Elyashberg and Lev Gribov propose a CASE methodology.
Elyashberg, M.E., et al. (1968). J. Applied Spectroscopy, 8: 189–191. DOI

1994: ACD/Labs is born!

ACD/Labs is established in Toronto, ON, Canada with only 2 staff members.
ACD/Labs is established in Toronto, Canada

1998: ACD/Structure Elucidator is born!

Structure Elucidator (SE) is originally based on 1D NMR and IR spectra, a DB of 400,000 fragments, and a filter containing spectrum-structure correlations in NMR and IR spectra.

2001: Hello, 2D NMR!

With the recent advent of 2D NMR experiments, heavier molecules can now be elucidated. This is the beginning of the molecular connectivity diagram.
Blinov, K.A., et al. (2001). Fresenius' J. Anal. Chem., 369: 709–714. DOI An expert system for automated structure elucidation utilizing 1H-1H, 13C-1H and 15N-1H 2D NMR correlations

2002: SE makes short work of large natural products!

Structures of 60 natural products of up to 65 skeletal atoms are successfully determined by Structure Elucidator.
Elyashberg, M.E., et al. (2002). J. Nat. Prod., 65(5): 693-703. DOI

2003: SE does the "impossible"

After ten years of human effort, the structure of quindolinocryptotackleine is solved with help from Structure Elucidator.
Blinov, K.A., et al. (2003). Magn. Reson. Chem., 41: 577–584. DOI Quindolinocryptotackieine

2004: SE is better and faster for complex natural products

Structure Elucidator's efficient processing of 2D NMR is found to be necessary to elucidate complex natural compounds, and significantly faster than other systems.
Elyashberg, M.E., et al. (2004). J. Chem. Inf. Comp. Sci., 44(3): 771–792. DOI

2005: A new dimension in SE!

V 9.0 NOESY/ROESY based algorithms are developed, as well as the ability to determine the relative stereochemistry and a 3D model of an elucidated structure. NOESY/ROESY based algorithms are developed

2006: Even more atoms!

Structure elucidator solves structures with up to 100 atoms.
Elyashberg, M.E., et al. (2006). J. Chem. Info. Model., 46(4): 1643–1656. DOI

2007: Perfect data not required

V 11.0 Fuzzy Structure Generation permits correct solutions in the presence of an unknown number of non-standard correlations with unknown lengths in 2D NMR data.
Elyashberg, M.E., et al. (2007). J. Chem. Info. Model., 47(3): 1053–1066. DOI Fuzzy Structure Generation

2008: Praise for SE

Structure elucidator is found to be the most advanced commercial expert tool, encompassing all features of other products but with even more advanced functionality.
Elyashberg, M.E., et al. (2008). Prog. Nucl. Magn. Reson. Spectrosc., 53(1—2): 1–104. DOI

2009: Symmetry is a problem of the past

For the first time, large symmetric molecules are elucidated from 2D NMR.
Elyashberg, M.E., et al. (2009). J. Cheminform., 1: 3. DOI

2010: SE makes sure you're on the right path

Literature revisions of published structures are used to demonstrate how Structure Elucidator can avoid incorrect hypotheses and aide evaluation of proposed structures.
Elyashberg, M.E., et al. (2010). Nat. Prod. Rep., 27: 1296–1328. DOI

2012: Extra, extra read all about it!

Contemporary Computer-Assisted Approaches to Molecular Structure Elucidations, a book featuring Structure Elucidator and describing the state-of-the-art in CASE systems is published.
Elyashberg, M.E., Williams, A.J., Blinov, K.A. (2012). Contemporary Computer-assisted Approaches to Molecular Structure Elucidation, RSC. DOI Contemporary Computer-assisted Approaches to Molecular Structure Elucidation

2014: SE joins the Spectrus Platform!

Structure Elucidator Suite transitions to the Spectrus Platform with full integration of NMR Workbook for unparalleled processing, interpretation, and elucidation power. SE joins the Spectrus Platform

2016: Learning to use SE just got easier!

ACD/Labs Structure Elucidation Tutorials, including in-depth examples for scientists to practice and learn the art of CASE, are provided as free downloads. The examples are discussed in "Computer-Based Structure Elucidation from Spectral Data" from Springer.
M. E. Elyashberg, A. J. Williams, Computer-based Structure Elucidation from Spectral Data. The Art of Solving Problems, Springer, Heidelberg, 2015. DOI
www.acdlabs.com/TeachingSE

2017: One step forward for dereplication!

For the first time, a database of known structures, taken from PubChem and ChemSpider, can be searched to identify if one's compound has already been identified. A database of known structures can be searched to identify if one's compound has already been identified

2019: Differentiate stereoisomers from NMR

Structure Elucidator makes it possible to elucidate stereoisomers from a flat 2D structure using NOESY/ ROESY spectra. Differentiate stereoisomers from NMR

2020: Same result in less time

Real-time generation and ranking of structures during elucidation allows NMR spectroscopists to identify the best structure even before the generation process is complete.

2021: The golden age of CASE is still to come

SE and the future of CASE is discussed in an MRC featured article, and it is predicted that the best is yet to come! Read more
Elyashberg, M.E., Argyropoulos, D. (2021). Magn. Res. Chem., 59(7): 669–690. DOI
Computer Assisted Structure Elucidation (CASE): Current and future perspectives

Resources

The second session in this two-part webinar series will continue with unknown structure elucidation using CASE. We demonstrate how by using a molecular formula, CASE can find the chemical structure that best fits the data.
Watch on Demand

Computer-Assisted Structure Elucidation (CASE) is a powerful approach for elucidating complex chemical structures. In a new featured article in Magnetic Resonance in Chemistry, ACD/Labs' Mikhail Elyashberg and Dimitris Argyropoulos discuss the most likely directions in which CASE will evolve based on its synergistic relationship with advances NMR experiments and computational chemistry.
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In this poster by taking advantage of recent programming developments, we will present approaches that enable structure elucidation, under conditions where the initial data contains many ambiguous assumptions. Examples will be presented, and the strengths together with the limitations of each approach will be discussed.
Read more

Complete the form below and our team will send you more information about the Structure Elucidator Suite promotion.

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