Hi All -
Here's my 2 cents...
> Date: Tue, 2 Apr 2013 07:27:08 +0200
> From: Greg Landrum <greg.land...@gmail.com>
> Subject: [Rdkit-discuss] Handling reaction stereochemistry
> To: RDKit Discuss <rdkit-discuss@lists.sourceforge.net>
>
...
> In [7]: rxn = AllChem.ReactionFromSmarts('[C:1]-O>>[C:1]-S')
> In [8]: ps = rxn.RunReactants((Chem.MolFromSmiles('F[C@H](O)Cl'),))
> In [9]: Chem.MolToSmiles(ps[0][0],True)
> Out[9]: 'F[C@H](S)Cl'
>
> It seems nice to be able to preserve chirality in these cases.
>
> The question that comes up is: "*Should* we be preserving chirality in
> these cases?". The change makes it impossible to indicate a reaction
> that scrambles stereochemistry. That doesn't seem right.
This should be the default behavior since it covers the vast majority
of rxns, chiral and achiral.
>
> So... the question to you guys: How should stereochemistry
> inversion/retention/loss be indicated in Reaction SMARTS?
This is my just my opinion... don't mistake me for an expert.
Stereocenter selectivity (or inversion) requires that the reaction
components be chiral.
In your example, C-O >> C-S is not chiral even if the C can map onto a
chiral reactant.
In contrast, F[C@H](O)Cl>>F[C@H](S)Cl is chiral, as is
F[C@H](O)Cl>>F[C@@H](O)Cl.
[C@]O>>C[@}S is not chiral due to insufficient neighbors being provided.
Having to specify the neighboring atoms is a pain and reduces the
transform's value for generic reuse..
But (in my experience anyway) stereoselective transforms should be
depicted with explicit stereocenters, i.e. with neighboring atoms (or
atom lists) present.
>
> Bonus points to anyone who can explain to me how the
> inversion/retention flags in RXN files should be handled. At the
> moment the RDKit uses what's in the products and ignores them in the
> reactants.
Without reminding myself about how RXN file inversion/retention flags work...
I would stick to treating transform atoms as chiral only if they are
marked as chiral AND their neighbors are represented explicitly.
(If that makes them achiral, they still do NOT stomp stereocenters in
chiral reactants.)
This should work with SMILES or RXN files.
Best regards -
- Robert
>
> -greg
>
>
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