Generate stereoisomers fails to generate all isomers

I am generating tetrahedral stereoisomers for a set of input molecules.  Some of the input molecules have specified tetrahedral centers, so "Protect tetrahedral stereo centers" is checked (= on).  The input structure CC1CC2CCC(C1)N2 should generate four stereoisomers, but only three are generated, and none of them have a wedge/dash bond at the carbon with the methyl substituent.  The correct output is obtained if "Protect tetrahedral stereo centers" is unchecked.

Please fix this so that the correct results are obtained when "Protect tetrahedral stereo centers" is checked.

 

 

Dear Tim,

thank you for your post. I could reproduce you observation in 6.0.0 version.

This looks to be a bug and I created a bug riport about it.

How urgent is this fix for you?

Thank you,

Miklos

Hi Miklos,

This is fairly important to me, as I’d like to use this calculation as
part of a routine process.  What I’d like to do is calculate the
tetrahedral stereoisomers (preserving tetrahedral stereoisomers which are
already specified) and then filter out the invalid 3D isomers.  So ideally this bug would be fixed in
conjunction with the bug I reported here: 
https://www.chemaxon.com/forum/viewtopic.php?p=46474#46474

Thanks,

Tim

Dear Tim,

We fixed the bug. It will be available in version 6.1.
Please see the attached picture. Is that what you expected?

Best regards,
Laszlo

> Please see the attached picture.  Is that what you expected?

No.

The input structure has three stereogenic centers and all three should be specified in each of the isomers generated.  In the output you posted, isomers #3 & #4 only have two of the three stereogenic centers specified --- neither one has a wedge/dash bond at the carbon with the methyl substituent.

The "Expected Results" in my original post shows the correct output.

Hi,

Thanks for your quick response.

In the output you posted, isomers #3 & #4 only have two of the three stereogenic centers specified --- neither one has a wedge/dash bond at the carbon with the methyl substituent

In these isomers the carbon with the methyl substituent is not chiral (*) (drawing the bond to the methyl with wedge or with dash would be the same structure, see attached image): wedge/dash on a bond connecting to a non-chiral would have no information content. This is the cause why stereoisomer enumeration currently not assigns wedge/dash bond to this atom.

We are very much interested in your further usage of the generated isomers and your point regarding the above reasoning.

(*) Isomers #3 and
#4 have only two stereocenters because the carbon with the methyl substituent has two
identical ligands; in isomers #1 and #2 these two ligands differ in the chirality of the two other chirality centers.

Thank you for the explanation --- I had missed the fact that the carbon with the methyl substituent is not a stereogenic center in isomers #3 & #4.   I now agree that isomers #3 & #4 are OK and that the output shown above is OK.

We are very much interested in your further usage of the generated isomers

What I want to do is generate the isomers, then filter out the invalid 3D isomers, so #3 &#4 will be eliminated from the result set.