User 74fd3a8edc
27-12-2007 15:09:19
I have created a general reaction file for the hydrolysis of secondary amides (bt0067) and it works well. However, when the query atoms are in a ring the result is a compound with generalized stereochemistry. I would like the reaction file to produce cis products from ring substrates. Please see the example I have given.
| Code: |
/home/sdml/umbbd/src/java> react -a changing -v -r ../molecules/bt0067.mrv "[O-]C(=O)C1=CC(=O)NC(=O)C1"
NC(=O)CC(=CC([O-])=O)C([O-])=O
NC(=O)CC(=CC([O-])=O)C([O-])=O
NC(=O)C=C(CC([O-])=O)C([O-])=O
NC(=O)C=C(CC([O-])=O)C([O-])=O
Total running time (ms) : 1649
Reaction setting (ms) : 1485
Reactant setting (ms) : 1
Reaction processing (ms): 163 |
The compound being tested is:
[O-]C(=O)C1=CC(=O)NC(=O)C1
All returned products have generalized stereochemistry but I would like to return the cis stereochemistry:
NC(=O)\C=C(\CC([O-])=O)C([O-])=O
How can this reaction file be modified to produce cis stereochemistry for the example compound above? I have tried standardization but it does not seem to work. Please see the attached reaction file (bt0067).
ChemAxon d76e6e95eb
27-12-2007 21:16:46
I understand the problem but I need to consult with the developers regarding the solution. I will get back with an answer in a week.
User 870ab5b546
04-01-2008 16:53:21
Your reaction definition is flawed. The L atom attached to C(3) in the starting material should be included in the product, as follows:
| Code: |
<?xml version="1.0" ?>
<MDocument>
<MChemicalStruct>
<reaction>
<propertyList>
<property dictRef="REACTIVITY" title="REACTIVITY">
<scalar><![CDATA[!match(ratom(1), "CC(C)(COP(O)(=O)OP(O)(=O)OCC1OC(C(O)C1OP(O)(O)=O)n2cnc3c(N)ncnc23)C(O)C(=O)NCCC(=O)NCCS", 1) && !match(ratom(1), "NC(CCC(=O)NC(CS)C(=O)NCC([O-])=O)C([O-])=O", 1)]]></scalar>
</property>
<property dictRef="EXPLAIN_REACTIVITY" title="EXPLAIN_REACTIVITY">
<scalar><![CDATA[Rule is blocked from acting on CoA and glutathione]]></scalar>
</property>
<property dictRef="EXPLAIN_STANDARDIZATION" title="EXPLAIN_STANDARDIZATION">
<scalar><![CDATA[Any ring with double bonds produces cis products]]></scalar>
</property>
<property dictRef="STANDARDIZATION" title="STANDARDIZATION">
<scalar><![CDATA[<?xml version="1.0" encoding="UTF-8"?>
<!-- Standardizer configuration file -->
<!-- This configuration file is created with ChemAxon Config Builder -->
<StandardizerConfiguration Version ="0.1">
<Actions>
<Transformation ID="Ring double bond to cis double bond 1" Structure="[*:4]@[C:3]@=[C:2]@-[*:5]>>[*:5]~[C:2]=[C:3]~[*:4]" Type="string" Groups="reactant1"/>
</Actions>
</StandardizerConfiguration>
]]></scalar>
</property>
<property dictRef="NAME" title="NAME">
<scalar><![CDATA[tertiary Amide -> Carboxylate + secondary Amine]]></scalar>
</property>
<property dictRef="EXPLAIN_EXCLUDE" title="EXPLAIN_EXCLUDE">
<scalar></scalar>
</property>
<property dictRef="EXPLAIN_SELECTIVITY" title="EXPLAIN_SELECTIVITY">
<scalar></scalar>
</property>
<property dictRef="TOLERANCE" title="TOLERANCE">
<scalar></scalar>
</property>
<property dictRef="EXPLAIN_TOLERANCE" title="EXPLAIN_TOLERANCE">
<scalar></scalar>
</property>
</propertyList>
<reactantList>
<molecule molID="m1">
<atomArray
atomID="a1 a2 a3 a4 a5"
elementType="O N C C C"
mrvMap="5 1 2 3 0"
mrvQueryProps="0 H1 L!H: 0 L!O:"
x2="-6.93 -4.62 -3.0799999999999996 -5.39 -4.619999999999999"
y2="0.0 -1.3336791218280357 -1.3336791218280357 0.0 1.3336791218280353"
/>
<bondArray>
<bond atomRefs2="a4 a1" order="2" />
<bond atomRefs2="a2 a3" order="1" />
<bond atomRefs2="a2 a4" order="1" />
<bond atomRefs2="a4 a5" order="1" />
</bondArray>
</molecule>
</reactantList>
<productList>
<molecule molID="m2">
<atomArray
atomID="a1 a2 a3 a4"
elementType="O O C C"
formalCharge="0 -1 0 0"
mrvMap="5 6 3 0"
mrvQueryProps="0 0 0 L!O:"
x2="4.62 6.93 6.16 6.9300000000000015"
y2="0.0 -1.3336791218280357 0.0 1.3336791218280357"
/>
<bondArray>
<bond atomRefs2="a3 a1" order="2" />
<bond atomRefs2="a3 a2" order="1" />
<bond atomRefs2="a3 a4" order="1" />
</bondArray>
</molecule>
<molecule molID="m3">
<atomArray
atomID="a1 a2"
elementType="N C"
mrvMap="1 2"
mrvQueryProps="0 L!H:"
x2="10.01 11.55"
y2="0.0 0.0"
/>
<bondArray>
<bond atomRefs2="a1 a2" order="1" />
</bondArray>
</molecule>
</productList>
</reaction>
</MChemicalStruct>
</MDocument> |
On your larger question, I think if you do a Molecule.setDim(2) on your SMILES substrate, the cis stereochemistry will be preserved in the product.
I think so because when I paste [O-]C(=O)C1=CC(=O)NC(=O)C1 into Marvin and submit it to my synthesis calculator with the corrected definition above, Reactor returns [NH2:1][C:2](=O)C\C(C([O-])=O)=[CH:4]/[C:3]([O-:6])=[O:5].[NH2:1][C:2](=O)C\C(C([O-])=O)=[CH:4]/[C:3]([O-:6])=[O:5] as its first product set and [NH2:1][C:2](=O)\C=C(/[CH2:4][C:3]([O-:6])=[O:5])C([O-])=O.[NH2:1][C:2](=O)\C=C(/[CH2:4][C:3]([O-:6])=[O:5])C([O-])=O as its second. (The map numbers are removed in subsequent processing.) Note that the double bond stereochemistries are specified and correct. Because I grabbed the substrate from Marvin, it must have been converted to 2D, rather than the 0D of SMILES strings.
User 74fd3a8edc
04-02-2008 18:50:53
Thank you for the reply. I updated the reaction definition as described above. The stereochemistry issue no longer seems to be a problem with the installation of JChem 5.0.
| Code: |
/home/sdml/umbbd/src/java> setCP
/home/sdml/umbbd/src/java> react -a changing -v -r ../molecules/bt0067.mrv "OC(=O)C1=CC(=O)NC(=O)C1"
NC(=O)C\C(=C/C([O-])=O)C(O)=O
NC(=O)C\C(=C/C([O-])=O)C(O)=O
NC(=O)\C=C(/CC([O-])=O)C(O)=O
NC(=O)\C=C(/CC([O-])=O)C(O)=O
Total running time (ms) : 3349
Reaction setting (ms) : 2854
Reactant setting (ms) : 4
Reaction processing (ms): 491 |