hi,
is there a general rule of what kind of column and MP for diastereomer sparation? the chiral column does not seem to work well, the C18 with RP looks working on derivatized ones, but not well on natural diastereomers.
i am working on a synthetic diastereomers from medicinal chemistry project, the usual C18 or phenyl-hexyl column for separation for marfey's derivatization for carboxylic acid to amide diastereomers does'nt work here. the molecule is of course not the same type of acid , but a alkyl chain with some pyrro rings.
any comments is welcome.

Hello Anonymous,

I use column of Beta-Cyclodextrin Chirex (Merck or Agilent) with good results.

Carlos Teixeira

thanks,
beta-CD needs at least 1 benzene rings to work, right? the guide book from cyclobond said so.
and do you run it with water/ACN and TFA?
my compound only has a 5 atom pyrro ring, i am not sure if it works with beta-CD.

Have you tried a graphite column? They are supposed to be good for the separation of diastereomers.

can you specify what kind of column is graphite column? where to find the info?
thanks very much, i am struggling here.

I would drastically change the pH and see if the deprotonation of the pyrro rings will make a difference in the selectivity

You can try beta-CD column, because beta-CD forms inclusion complex also with other rings not only with benzene ring. I do not suggest the use of TFA, rather methanol or ethanol. You can use also cyclodextrin derivatives (even ionic derivatives) as mobile phase additive on C18, C8 or CN columns.

There are 2 "graphite" columns that I know of:

Hypercarb

http://www.thermo.com/eThermo/CDA/Products/Product_Detail/1,1075,1000002109518-115-X-1-12739,00.html

ZirChrom-CARB

http://www.zirchrom.com/CARB.asp

If you are working with an acidic compound, the ZirChrom-CARB column would probably not work very well.

thanks.
i am in the process to obtain a carbon column from hypersil.
to UWE, the chiral centers are not on the ring, so i would think they will behave similar for both diastereomers under different pH, right?
i tried beta-CD(cyclobond 2000 I) yesterday with ACN/water, no TFA, didn't get the separation. just 1 peak. have no idea what to change from there. add TEAA to change pH?

I still would try the pH shift. The reversed-phase interaction depends on the behaviour of the entire molecule. I have seen some surprises, when the charge on the molecule changes. (I'll send you a publication, if you send me your address.)
Of course, this is a shot in the dark, but I would not rule it out.

Can we go back here a bit. Are you trying to
separate diastereoisomers or enantiomers?

What was the ratio of ACN/water in the mobile phase on Cyclobond column? I suggest the change of pH, and use low solvent ratio in the mobile phase.