SDFs for CAS# determination - problem with stereochemistry

Hi all,

I try to prepare SDFs to be used for CAS number determination by Chemical Abstracts Service. My company is specialized in nuceotide chemistry, and we need to determine if there are already CAS numbers assigned for a large number of our products. This is done by CAS, we need to deliver the SDFs.

Nucleotides are chiral compounds, so stereochemistry is an issue. So far, my SDFs have not worked for CAS. I attached an example, obviously its stereochemistry is not correct, so their search fails. The main problem seems to be the foregound bond in the ribose: while I can depict the stereochemistry of the molecule by placing the wedge bonds on the left and the right, I can't draw a thick "foreground" bond using Marvin. It can only draw thin single bonds.

This is what CAS asked me when I had sent them the attached file:

1)  Can you find in the software if there is a place to tag this

substance as having "absolute" stereochemistry?



2)  Can you model your nucleotides and place the wedge and dash bonds on

the sugar on the 4 centers to depict that absolute stereochemistry?

Does anyone have an idea how I can accomplish this using Marvin? Perhaps some of you have already worked with CAS and can give me a hint - so far this was a "black box" for me (I sent files and they said these don't work, and they are  unable to provide me with a template).

 

Thanks for any help!

 

Best wishes,

 

Thomas.

Hi,

I have not used CAS yet, but I think their main problem is that the absolute flag is missing.

You can set the absolute flag for the molecule in msketch:

Structure -> Add -> Absolute Stereo (CHIRAL)

(Or you can set it in the counts line of the sdf file with a text editor. See the sdf file formats -ctfile definitions- at the mdl site.)

Andras

Dear Andras,

 

thanks a lot! I must have missed this option. I will prepare a new SD file and will send it to CAS to try it out.

 

Best wishes,

 

Thomas.

Dear Andreas,

I think you missunderstand the use of stereochemistry specifiers.

They do not mean, that the atoms at the thick end are in the foreground. By using the wedges, you specify whether a chrial atom has R or S configuration.

This depends on the priority of the atoms and this is why there is no thick bond option for the foreground bond (there is no foreground in 2D). As there are four atoms which are chiral, you need to specify the according number of wedges (see the attached file).

By using the conformers plugin you can easily check if you entered the correct configuration.

Regards, Ingo

Dear Ingo,

Thank you for the clarification.

You are right. In file NU-101_acid.sdf only 2 atoms has defined chirality with indexes 27 and 29.

The chirality of the atoms 30, 31 are still not defined.

Thomas, I think you should define them also as Ingo pointed out.

 

Andras

Dear Ingo and Andras,

 

you are right - stereochemistry of all these chiral atoms will very likely have to be defined so CAS search will work. I will give Ingo's corrected file a try as well.

 

Thank you guys for all your help!

 

Merry Christmas + a happy new one,

 

Thomas.

Hi Ingo,

 

SUCCESS! This one worked well for CAS. So now I know what to do and how to proceed.

 

Have a joyous Christmas time!

 

Best wishes,

 

Thomas.