No conformers with equatorial group

Hi

Some information for conformers plugin developers:

Conformers plugin (MarvinSketch 5.3.0.1) for the substance

(1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol

gives conformers with axial isopropenyl group only.

But by NMR experimental data and by DFT calculations there are conformers with equatorial isopropenyl group and the most stable conformer of this substance posesses such group.

Regards,

Alexandr

Hi Alexandr,

Thank you for reporting this axial-equatorial issue. An already known bug at the buliding process is the reason of this symptom. Sometime the atomic sequence in the molecule affects the conformation to be generated.

We are working on the solution.

To temporary circumvent this issue the the atomic sequence should be changed. Luckily for the current molecule the "right" sequence can be obtained simply by copy/pasting the IUPAC name

"(1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol"

into an msketch window and then the 3D structure can be instantly generated by [ctrl]-3.  In this case the equatorial position will be favored.

Our force field estimates the equatorial position about 2kcal/mol lower in energy than the axial.

Thank you again.

Kind Regards,

Adrian

 

genaev wrote:

Hi Alexandr, Thank you for reporting the axial/equatorial question. This is a special case of a general known  issue.   Some information for conformers plugin developers: Conformers plugin (MarvinSketch 5.3.0.1) for the substance (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol gives conformers with axial isopropenyl group only. But by NMR experimental data and by DFT calculations there are conformers with equatorial isopropenyl group and the most stable conformer of this substance posesses such group. Regards, Alexandr

Hi Adrian,

Thank you very much for the method to get conformers of my compound with equatorial isopropenyl group.

But there is another problem. This method gives only equatorial conformers (in 32.5-40 kkal/mole interval) while axial conformers are rather stable too.

Solution for me (for future) would be to freeze equatorial or axial position of some group in cycloxexane-like system and to process two sets of the conformers individually. I find old post about absence of direct tool to specify the axial or equatorial position of a substituent, but may be situatuion is changed now?

 

The best regards,

Alexandr

Hi Alexandr,

thank you for your interesting link on the conformational analysis.  I am afraid the situation regarding to the axial/equatorial user constraints has not been changed yet. We can think on the implementation of this feature only on a longer term.

However here is a workaround to the issue of generating axial / equatorial in the desirable positions:

The atom numbering of the core scaffold defines the position of the isoproenyl moiety to be generated.

I attach two images with the scaffold numbering produces axial and equatorial positions. Whenever you want equatorial use the first scaffold and for axial  use the second.

This is not elegant I know but may helps.

Regards,

Adrian