[endophytic]

Hello board !

I'd like to synthesise AHL analogues (Acyl Homo Serine Lactone).
Globally a coupling between a carboxylic acid and a primary amine.






The thing is I would like my reaction to retain the original stereochemistry of the homoserine.
So I guess that the use of a coupling additive such as HOBt is necessary. Will it do the trick ?

Another concern I have is the stability of the lactone during the reaction or workup.
Do you think it might open ?

Finally what would you best guess be for Coupling agent (I have DCC or EDAC)  and solvent (DCM, DMF, THF) ??
Is the addition of a base like TEA suggested ?

Do you think the sequential order I add my reagents to the mixture is important ?  (seems to me I've read this about peptide coupling can't remember where)


Thank you all !


E.

[Dan]

You should really do the background research yourself before asking here. This compound has been prepared before in >99% ee.

Spring Tet. Lett., 2011, 52, 3291

Procedure is in the supplementary data

[opsomath]

So, doing quorum signalling research eh?

This should be a simple and easy reaction using any amine coupling procedure.

[endophytic]

Hi opsomath, hi Dan,

Thank you for the replies.

Dan, I do know how to use Google Scholar and did typed "AHL synthesis" in it. And had this paper.
If I come on these forums it is to have interaction with people that have a better knowledge of chemistry than I do.
I feel a bit lost sometimes starting my little synthesis with the low org. chem baggage I have.
That's why I come here, to have explanation on particuliar reagents, their role, suggestions, "savoir faire" ... in brief many subtilities that aren't allways in the papers. I hope you understand. Nevertheless thanks for the link. 

I asked my question in the original post because I saw many AHL preparation involved amine reaction with an acyl chloride. But I dont want to pass by acyl chloride. (I have to say a that point that I don't dispose of all the reagents I'd like in my lab )

So i thaught of a coupling mediated by DCC or EDAC.
In the paper you linked, Dan, they use DMAP and EDAC. Here what is the role of DMAP  ? Is it used to maintain the amine in it's non protonated form (as would be the role of TEA as explained to me magician4 here http://www.chemicalforums.com/index.php?topic=69371.0) I also saw it was use as additive for coupling of α,α-dimethyl aminoacids. In this case it's role would be similar too HOBt is that it ?

So. What's the paper of this DMAP here ?

I don't have DMAP. What do I replace it by ? HOBt ? TEA ? Both ?

Thanks for your advices 

[Dan]

Dan, I do know how to use Google Scholar and did typed "AHL synthesis" in it. And had this paper.
If I come on these forums it is to have interaction with people that have a better knowledge of chemistry than I do.
I feel a bit lost sometimes starting my little synthesis with the low org. chem baggage I have.
That's why I come here, to have explanation on particuliar reagents, their role, suggestions, "savoir faire" ... in brief many subtilities that aren't allways in the papers. I hope you understand. Nevertheless thanks for the link. 

Sorry if I was blunt, but we get a lot of people posting without showing what they have researched themselves. In most cases it is because they have not bothered to do any research themselves. You posted without showing any evidence of checking if the compound has been made before, so I assumed you hadn't checked - it is always best to show your working.

It would have been useful if you had mentioned that you had read the paper and explained why you did not want to follow their procedures in your first post.

So. What's the paper of this DMAP here ?

I don't have DMAP. What do I replace it by ? HOBt ? TEA ? Both ?

Thanks for your advices 

DMAP is used as a nucleophilic catalyst, see:

http://en.wikipedia.org/wiki/Steglich_esterification

In this case it is also used as a stoichiometric base (they used the HBr salt of the aminolactone).

[endophytic]

Ok. So I guess TEA+HOBt could replace the DMAP catalyst ?

1.3eq HOBt, 2 eq TEA would this do the trick ?

What about lactone opening ? Should this be a concern in basic cond it might open right ?


Thank you for the advices ...