Re: [Rdkit-discuss] mass replacement of External R-groups with many substituents

[Greg L. <gre...@gm...>]

Combining Steve's and Chris' answer gets to how I would do it with
reactions:

In [17]: core = Chem.MolFromSmiles('*c1c(C)cccc1(O)')

In [18]: chain = Chem.MolFromSmiles('CN*')

In [19]: rxn =
AllChem.ReactionFromSmarts('[c:1][#0].[#0][*:2]>>[c:1]-[*:2]')

In [20]: ps = rxn.RunReactants((core,chain))

In [21]: Chem.MolToSmiles(ps[0][0],isomericSmiles=True)
Out[21]: 'CNc1c(C)cccc1O'

If you can generate your sidechains in such a way that the atom you want to
attach to the core is the first one (atom zero), there's a somewhat easier
way to do this kind of simple replacement:
In [29]: chain2 = Chem.MolFromSmiles('NC')

In [30]: ps2 =
Chem.ReplaceSubstructs(core,Chem.MolFromSmarts('[#0]'),chain2)

In [31]: Chem.MolToSmiles(ps2[0],isomericSmiles=True)
Out[31]: 'CNc1c(C)cccc1O'

The reaction-based approach is, however, far more flexible.

We've talked about adding a simple function for doing sidechain-core
enumeration but I'm pretty sure it hasn't yet actually been done.

-greg




On Thu, Mar 16, 2017 at 6:16 PM, Stephen Roughley <
s.d...@go...> wrote:

> You can match a dummy atom (*) with the SMARTS [#0]
>
> Steve
>
> On 16 Mar 2017 16:43, "Chris Earnshaw" <cge...@gm...> wrote:
>
>> Hi Brian
>>
>> I'm by no means an expert in RDKit with Python, but until someone else
>> comes along, here are a few thoughts.
>>
>> Your reaction SMARTS specifically defines aromatic carbons joined by
>> single bonds which won't match an incoming benzene ring, and it's a bit
>> redundant to specify that aromatic carbons are in rings. It's possibly also
>> neater to specify the ring closure if you want to include the whole ring.
>> Finally, I don't think that you can specify dummy atoms in a reaction
>> SMARTS as you're attempting (it certainly doesn't work for me with R and
>> R1) but you certainly can specify 'placeholder' atoms using real elements.
>> I've found U, V & W handy for this in the past.
>>
>> A small Python script with a modified SMARTS which works for me is -
>> from rdkit import Chem
>> from rdkit.Chem import AllChem
>> rxn = AllChem.ReactionFromSmarts('[c:1]1[c:2][c:3][c:4][c:5]([U:7])[c:6]1.[V:8]-[*:9]
>> >> [c:1]1[c:2][c:3][c:4][c:5](-[*:9])[c:6]1')
>> ps = rxn.RunReactants((Chem.MolFromSmiles('c1ccccc1[U]'),Chem.
>> MolFromSmiles('[V]Cl')))
>> Chem.MolToSmiles(ps[0][0])
>>
>> This returns 'Clc1ccccc1'.
>>
>> Unless you have some specific reason to include the complete benzene
>> ring, the reaction SMARTS can be simplified a lot further, to -
>> [c:1][U:2].[V:3]-[*:4] >> [c:1]-[*:4]
>> This will carry out your virtual reaction on any aromatic carbon carrying
>> the appropriate placeholder element.
>>
>> I'd be interested to learn if there is an approved way to mark
>> substitution positions in reactions like this without having to resort to
>> the cheat of using obscure elements.
>>
>> Regards,
>> Chris
>>
>> On 15 March 2017 at 23:20, Bennion, Brian <ben...@ll...> wrote:
>>
>>> Hello All,
>>>
>>>
>>>
>>> I have looked around the email list and studied the daylight guide as
>>> well as the opensmiles website in hopes of solving my problem.  External
>>> r-groups is a proposed extension but that is all I could find.
>>>
>>>
>>>
>>> It is possible that I have made it too complicated though.
>>>
>>>
>>>
>>> In discussions with my synthetic chemist we came up with 27 substituents
>>> two place around our molecule scaffold.
>>>
>>> I labeled the scaffolds with R1 in the position that the substitution
>>> will occur and attached a dummy label to the substituents.  I thought that
>>> I could do a simple replacement rxn.  However, I have not been successful.
>>>
>>>
>>>
>>> The smarts string so far is listed below.
>>>
>>>
>>>
>>> AllChem.ReactionFromSmarts('[c;R:1]-[c;R:2]-[c;R:3]-[c;R:4]-
>>> [c;R:5]([R1;!R:7])-[c;R:6].[R:8]-[*:9] >> [c;R:1]-[c;R:2]-[c;R:3]-[c;R:4
>>> ]-[c;R:5]([*:9])-[c;R:6]')
>>>
>>>
>>>
>>> Basically just adding a group to positions along a benzene ring
>>>
>>>
>>>
>>> Thanks
>>>
>>> Brian Bennion
>>>
>>>
>>>
>>>
>>>
>>>
>>>
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