8. Known issues with stereochemistry preservation
Older Chemistry Development Kit (CDK) versions (and hence older CDK-Scaffold versions as well) had issues with correctly preserving double bond stereochemistry configurations in the event of atom removals. This page documents these issues with one example molecule from the test class, with respect to the specific versions.
The test method `stereoFragmentationTest()` in `ScaffoldGeneratorTest` creates parent scaffolds according to the scaffold tree rules of the following molecule, which contains two double bonds with defined stereo configurations:
The double bond stereochemistry is retained until one of the four substituents surrounding the double bond is removed:
The (main) scaffold of the molecule is created correctly (left), but already after the first ring removal, all double bond stereochemistry is lost (right):
This problem was reported in this issue and fixed prior to the CDK 2.12 release.
The double bond stereochemistry preservation is mostly fixed again, but now there is the problem that the stereo configuration changes (in this case) during the ring removal. The figures below illustrate this switch between two intermediate steps in the generation of all parent scaffolds:
This problem was reported in this issue and fixed in the CDK main repository prior to the CDK 2.13 release.
In the latest CDK and CDK-Scaffold release 2.13, this issue is now fixed. All parent scaffolds retain the correct stereo configuration as long as possible (all scaffold tree parent scaffolds are listed below):
