[cowgalT]

Hi,

I've been doing an HPLC experiment on cinchona alkaloids and I want to explain why Quinidine eluted from the column before Quinine, in terms of its polarity.
I was just wondering if any of you know any know of any good sites or could help me? I know the basics of why molecules are polar etc but these are quite large compounds and im just totally thrown as to where to start with them. 

Many thanks!

[Arkcon]

Well, there has to be some reason, but it can be very obscure.  Maybe if you just list the functional groups that differ between them, you can see a difference.  Or it could just come down to which one has more carbons per polar functional groups.

[Pradeep]

Arkcon,

Those two compounds are optical isomers are having identical functional groups. So, the routine explanation is not working. According to my knowledge an "optical active stationary phase" should be used to separate these two compounds.

And, cowgalT, you have not mentioned about the stationary phase which was used for your HPLC study!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! (And mention about the mobile phase also)

To try for an explanation we need that information also.

[cowgalT]

Ah yeah sorry for not mentioning the stationary phase!
I used a bonded silica phase with 5μm particles.
The mobile phase was 70% phosphate buffer (pH3), 30% methanol.

[Arkcon]

If it is a chiral bonded phase, that would explain it.  If it isn't a chiral phase, it may still separate optical isomers, but I don't have that reference handy -- I will look when I have some more time.  You should start looking along those lines yourself, and I'll try to find what I'd heard about mechanisms of chiral separation on "standard" phases.  Although, your standard linear C18 bonded phase may not be what I'm thinking of, it may require normal phase, and tour eluent doesn't seem to support that.

[Pradeep]

cowgalT,

This doesn't give any sense. Bonded silica phase  means, what ever your stationary phase is chemically bonded to silica support. The compound which is bonded to silica is mainly responsible for the separation. So you should check which bonded silica phase was that?

[cowgalT]

Thanks Arkcon,

sorry, I used an ODS column (C18) if that helps

[fledarmus]

From what I can tell, these are diastereomers rather than enantiomers. When you look at the stereochemistry around the quinuclidine system, there are a lot more than just 1 stereocenter, most of which are identical between the two molecules. This would explain why you could separate the two in an achiral system; if they were enantiomers they would not be separable in an achiral system. A C18 column has no chirality, and there was no mention of a chiral auxiliary in the solvent system.

As for trying to determine which is more polar and would thus come off first from the C18 column, that's very difficult to do by eye between two compounds that have identical connectivity and functional groups. It's possible that an energy minimization followed by a polarity calculation and simulated interactions between that model and the C18 would yield a calculated binding difference, but easier just to run the two through a column and find out.

[Pradeep]

This pubmed paper says those are optical isomers.

http://www.ncbi.nlm.nih.gov/pubmed/10774629

This is what I refereed.

[fledarmus]

If by optical isomers, they mean enantiomers, this is wrong. If by optical isomers, they mean stereoisomers as opposed to structural isomers, this is true. The two compounds are diastereomers, identical at 3 chiral centers and differing at the other two.

I have attached the structures of the two compounds below, with the chiral centers marked. These are from a SciFinder search, and the file names include the CAS numbers.

[Pradeep]

Yes. This can explain our question.

[cowgalT]

From the background reading I have already done, I am lead to believe that quinidine is a diastereoisomer of quinine. But both can exist as their own optical isomers.

Thanks fledarmus, that helps quite a bit!