Issue with Axial/Equatorial Stereochemistry Preservation

Hello

We are experiencing an issue with the preservation of axial or equatorial groups in a chair conformer that contains a bridgehead atom.  Marvin views these molecules as the same which creates issue while using chemaxon as the backend for our compound registration system.   I have attached the base structure with A/E configs which result in the same structure.  Is there a way to distinguish these as separate structures?  I tried a few other conventions but made no progress.

Thank you

Dennis

 



Hi Dennis,

I'll examine this issue and see what can we do.

Andras

Hi Dennis,

Actually we accept Nitrogen as stereocenter if it is bridgehead atom or if it is in three membered ring .

But the nitrogen in the picture is not bridgehead.

"A bridgehead is any skeletal atom of the ring system which is bonded to three or more skeletal atoms (excluding hydrogen)."

I think the Nitrogen atom you have presented don't have enough energy barrier so due to the inversion, the nitrogen will not be an active stereocenter.

Andras

Andras

Thank you for the reply, that makes some sense. How about the following structure where R is an alkane of length greater than 3 carbons?  It would seem like inversion may not place in the following

Dennis

Hi Dennis,

My feeling is that the Nitrogen in the molecule you have presented still not be active stereocenter.

We should calculate the energy barrier for the inversion to tell if it can or cannot be active stereocenter, but I have not done it.

We treat the stereochemistry of Nitrogen based on general assumptions see for example

Stereochemistry Conformation and Mechanism By P.S. Kalsi

Please let me know some references if you disagree.

 

Andras

Andras

Thanks for the reply, I agree with regard to the nitrogen not being chiral in this sense.  What I am concerned about is the equatorial Methyl and axial hydrogen at the C2 position.  There does not seem to be any preservation of this stereochemistry even with the nitrogen bridge atom (sorry for the confustion earlier in calling it the bridgehead).  Let me speak with the chemist who reported this a bit and get back to you with a further explanation, but I think we should be able to distinguish between an C2 methyl (eq) and C2 methyl (axial)?  The nitrogen (or any atom creating this bridge) though capable of inversion should lock this structure in the chair conformation and therefore the ax/eq positions at C2 should be preserved. 

Dennis

Dennis,

You have posted the picture, but not the original MRV code.  I suspect that the picture you have drawn is in 2D.  Marvin does not understand 2D perspective drawings to carry any 3D information.  If you want to show tetrahedral geometry in a 2D drawing, you need to use bold and hashed bonds.  By contrast, in a 3D Marvin drawing, the stereochemical information is inherent in the coordinates of the atoms, and bold and hashed wedges are ignored. So use the following 2D MRV, or clean it in 3D and use the result.

<?xml version="1.0" ?>

<cml>

<MDocument>

  <MChemicalStruct>

    <molecule molID="m1">

      <atomArray>

        <atom id="a1" elementType="C"

              x2="-1.649999976158142" y2="-3.8499659853675148" />

        <atom id="a2" elementType="C"

              x2="-2.9836693172064006" y2="-4.619982925926555" />

        <atom id="a3" elementType="C"

              x2="-2.9836693172064006" y2="-6.160016807044636" />

        <atom id="a4" elementType="C"

              x2="-1.649999976158142" y2="-6.930033747603677" />

        <atom id="a5" elementType="C"

              x2="-0.3163306351098836" y2="-6.160016807044636" />

        <atom id="a6" elementType="C"

              x2="-0.3163306351098836" y2="-4.619982925926555" />

        <atom id="a7" elementType="N"

              x2="-1.649990195378365" y2="-5.389982925926555" />

        <atom id="a8" elementType="C"

              x2="-4.523669317206401" y2="-6.160016807044636" />

        <atom id="a9" elementType="H"

              x2="-3.3822506466642825" y2="-7.6475425795298015" />

        <atom id="a10" elementType="C"

              x2="1.017348486718152" y2="-3.849982925926555" />

      </atomArray>

      <bondArray>

        <bond atomRefs2="a1 a2" order="1" />

        <bond atomRefs2="a1 a6" order="1" />

        <bond atomRefs2="a2 a3" order="1" />

        <bond atomRefs2="a3 a4" order="1" />

        <bond atomRefs2="a4 a5" order="1" />

        <bond atomRefs2="a5 a6" order="1" />

        <bond atomRefs2="a2 a7" order="1">

          <bondStereo>W</bondStereo>

        </bond>

        <bond atomRefs2="a4 a7" order="1">

          <bondStereo>W</bondStereo>

        </bond>

        <bond atomRefs2="a3 a8" order="1">

          <bondStereo>W</bondStereo>

        </bond>

        <bond atomRefs2="a3 a9" order="1">

          <bondStereo>H</bondStereo>

        </bond>

        <bond atomRefs2="a6 a10" order="1">

          <bondStereo>W</bondStereo>

        </bond>

      </bondArray>

    </molecule>

  </MChemicalStruct>

</MDocument>

</cml>

-- Bob

Bob

Thanks for the reply, this is very helpful.  

Dennis