Reactions creating wiggle bonds in products

We are currently using jchem version 3.2.3 and some of our reactions are creating "wiggle" bonds. This occurs with any substrates that have a ring with a double bond and is indicating that the stereochemistry of a double bond could be either cis or trans. Unfortunately, this is creating some problems with our system and we are wondering if there is a way to have the reaction produce trans products only.





For instance, using bt0024, for a reactant with a double bond (but no ring) creates the correct stereochemistry.

Code:

react -a changing -v -r ../molecules/bt0024.mrv "C\C=C/OC(C)=O" C\C=C/O CC([O-])=O

But using a reactant with a ring and a double bond gives an ambiguous result.

Code:

react -a changing -v -r ../molecules/bt0024.mrv "[O-]C(=O)C1=CCC(=O)O1" OC(=CCC([O-])=O)C([O-])=O OC(=CCC([O-])=O)C([O-])=O

We would like the product of the above reaction to be:


O\C(=C/CC([O-])=O)C([O-])=O


Is there a way to restrict the rule so that it produces only the trans product?


Thank you for your help.

Hi,





There is no cis/trans information in your second input molecule ("[O-]C(=O)C1=CCC(=O)O1"), that's why the double bond stereo type in products is unpredictable by Reactor (related documentation: http://www.chemaxon.com/jchem/doc/user/Reactor.html#cistrans). In fact double bonds in rings usually do not hold this kind of stereo information.





Handling the problematic double bond in the reaction scheme also can not be done easily, because it is not required to be present in the reactant, and the reaction scheme is not supposed to hold any information about it.





The problem can be solved using reactant standardization. I have specified a "Ring double bond to cis double bond" transform (SMARTS: "[#6:4]@-[C:3]@=[C:2]@-[O:1]C=O>>[#6:4]\[C:3]=[C:2]/[O:1]C=O") in the reaction as reactant standardization. This transform will convert only the ring double bonds in molecules that are suitable reactants for your reaction, and put the required stereo information into them in the reactant standardization step (before processing the reaction). Using reaction file that contains this reactant standardization (bt0024rs.mrv - attached) the reaction will produce the products you expect.

Code:

react -a changing -v -r bt0024rs.mrv "[O-]C(=O)C1=CCC(=O)O1"            O\C(=C/CC([O-])=O)C([O-])=O O\C(=C/CC([O-])=O)C([O-])=O

Reactant standardization can be specified in command line too, so this also works:

Code:

react -a changing -v -S "[#6:4]@-[C:3]@=[C:2]@-[O:1]C=O>>[#6:4]\[C:3]=[C:2]/[O:1]C=O" -r bt0024.mrv "[O-]C(=O)C1=CCC(=O)O1" O\C(=C/CC([O-])=O)C([O-])=O O\C(=C/CC([O-])=O)C([O-])=O

Best regards,


Zsolt

We have tested the standardization and it works quite well! Thank you for your help.

We have written a more general form of the reactant standardization above to encompass any ring with a double bond and carbon atoms. Here are the SMARTS:


[#6:1]@-[C:2]@=[C:3]@-[#6:4]>>[#6:4]\[C:3]=[C:2]/[#6:1]


This works well for most of our reactions; we simply change some of the carbons to other atoms depending on what atoms are in the reaction. We are still using jchem 3.2.4 and Reactor GUI.





However, we are having trouble when there is a ring with more than one double bond. For instance, with this seven membered ring with 2 double bonds, O=C1OC=CCC=C1 as a substrate, our product is O\C=C/CC=CC([O-])=O (using the updated bt0024 reaction which I have attached).

Code:

react -a changing -v -r ../molecules/bt0024.mrv "O=C1OC=CCC=C1" O\C=C/CC=CC([O-])=O O\C=C/CC=CC([O-])=O

One of the double bonds contains stereochemistry and the other does not. We would like both bonds to be cis. Besides adding more and more reactant standardizations for every possible scenario of double bonds in a ring, is there a general way to fix this? Ideally, we would like something that could handle any number of double bonds in a ring with any number of members, but our system contains mostly 8 membered rings or less.