Hi John,

Thanks for your comments. They are very refreshing to me, so much = that they need some more explanation. J

So, if I understand correctly, the 1st part of your answer = (i.e. the edge reduction procedure) is a graph theoretical method to = find bridgehead atoms in bridged systems. Let me neglect this part for = now.

The 2nd part is the actual trans-linked bridge = identification procedure. Conceptually I understand that the rotations = round the 2 bridgehead atoms should be reverse of each other to get the = cis-linked bridge, when iterating in the same order over the common = ligands.

But, how do you translate the absolute configuration (R/S) of the = bridgehead centers into the “relative parity” of one center = to the other relative to the non-shared vertex? The norbornane example = has two S absolute configurations, meaning that the prioritized ligands = turn both in counterclockwise sense. If you add a hydroxyl group to one = of the secondary carbons in the same cis-linked structure, then suddenly = the absolute configuration of one of the bridgehead atoms changes from S = to R.

Regards,

Nick

From:= = John May [mailto:johnmay@ebi.ac.uk]
Sent: Wednesday, August = 21, 2013 6:09 PM
To: Nick Vandewiele
Cc: = cdkuser
Subject: Re: [Cdk-user] stereoisomer generation - = identifying physically impossible, strained = stereoisomers

Sounds = cool, Not aware of any open alternatives I'm afraid but might have = an idea.

One way I can think of is to iteratively collapse = edges of the graph to find two adjacent tetrahedral centres which share = 3 vertices. You could restrict this to only collapse cyclic = parts - perhaps restricted to a given ring size which is defined as = rigid. When you find two centres which share three vertices = compute the relative parity of one (relative to the non-shared vertex). = Then the relative parity of the other (again relative to the non-share = vertex) but keep the ordering of the shared vertices the same. If = the configuration is valid the parties should be inverse of each = other.

The only tricky part there is the collapsing but might = not be too bad. Not a general method but reducing all cyclic edges where = both vertices are not a bridge-head tetrahedral centre might be starting = point.

Hope it helps,

J

On 21 Aug 2013, at 22:00, "Nick Vandewiele" = <Nick.Vandewiele@UGent.be>= wrote:

Hi,

=

I am = working on a tool (using CDK) that generates all possible stereoisomers, = based on a molecule with unspecified stereocenters. I don’t know = of a free/open tool that does this (besides ChemAxon’s Marvin, = which doesn’t have an API, I = assume)

=

One of the = problems is the following:

How can = one identify if the 2 bonds connecting the bridgehead atoms to the = bridge atom are at the same side of the plane? Think of norbornane with = the bond from the bridgehead atom pointing upwards to the bridge atom, = the bond from the other bridgehead pointing downwards. I can only use = the absolute configurations (or stereo parities if you will) of the = bridgehead atoms as the source of info to determine = this.

=

One idea = was the following: generating up/down bonds based on the order of the = ligands (retrieved from the absolute configuration). Then, check if the = bridge bonds are both up or both down. This is not enough: if = you’re unlucky, the other bonds of the bridgehead atoms will have = the up/down stereo specification, while the bridgehead bonds will be = “flat”.

=

Any = thoughts?

Nick

=

<image00= 4.png>

=

=

<oledata.mso>---------------------------------------= ---------------------------------------
Introducing Performance = Central, a new site from SourceForge and
AppDynamics. Performance = Central is your source for news, insights,
analysis and resources = for efficient Application Performance Management.
Visit us today!