Re: [Rdkit-discuss] Problem finding potential stereo-centres in bridged bicyclics involving 4-membered rings?

[James D. <J.D...@ve...>]

Hi Greg,

Thanks for the response (and sorry to be the bearer of bad news!).
Issue added:  https://github.com/rdkit/rdkit/issues/4155

Kind regards

James

From: Greg Landrum <gre...@gm...>
Sent: 19 May 2021 14:59
To: James Davidson <J.D...@ve...>
Cc: rdk...@li...
Subject: Re: [Rdkit-discuss] Problem finding potential stereo-centres in bridged bicyclics involving 4-membered rings?

Hi James,

I don't think that's the same bug as #3490. I think it's something different; "yay".
;-)

It would be great if you could file a github issue for this.

Thanks,
-greg


On Wed, May 19, 2021 at 3:20 PM James Davidson <J.D...@ve...<mailto:J.D...@ve...>> wrote:
Dear All,

I’ve got a strong suspicion that what I am seeing is related to the open issue 3490 (https://github.com/rdkit/rdkit/issues/3490), but as I can’t seem to find a mention of a non-spiro problem then I thought I would share.
Tested in 2020.09.4 and 2021.03.2 with the same result.

smi_list = ['CC1CCC(CC1)C(N)=O', 'CC12CCC(CC1)(C2)C(N)=O', 'CC1CC(C1)C(N)=O', 'CC12CC(C1)(CC2)C(N)=O']
for smi in smi_list:
    mol = Chem.MolFromSmiles(smi)
    display(show_mol(mol, size=(450, 200)))  # wrapper function for new drawing code in jupyter
    print(list(Chem.FindPotentialStereo(mol)))
    print(Chem.FindMolChiralCenters(mol, includeUnassigned=True, useLegacyImplementation=False))

The 4 cases are:

  *   Symmetrically-disubstituted 6-membered ring
  *   A bridged version (using a 1-atom bridge to avoid a completely symmetrical product)
  *   Symmetrically-disubstituted 4-membered ring
  *   A bridged version (this time using a 2-atom bridge to avoid symmetry)

And this is what I see:

[cid:image001.png@01D74CCD.B6F2A180]

In the case of the bridged 4-membered ring (or bridged 5-membererd ring, depending on your viewpoint!), FindPotentialStereo() fails to identify the two potential stereo atoms.
If anyone can spot if this is the same issue as 3490, or something different, then that would be appreciated!

Kind regards

James
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