Enumeration Problem with an Anhydride

I can't get Reactor to use the attached anhydride in my enumerations.  All other anhydrides work fine.  I can't figure out why this one fails. 

Could you attach the reaction schema? Without it we can't tell why it fails.

Zsolt

I realize my first post was rather short and lacked a lot of information.  I've been enumerating libraries of compounds which involve the acylation of a primary amine with various cyclic anhydrides. I created the reaction scheme in Reactor and it works fine for every anhydride I've tried except for the one in the file attached to my first post.  For some reason this particular anhydride fails to undergo the reaction.  I've tried a couple of different reaction schemes made in Reactor with the same result.  I've attached a file to this post a file containing both the usuccessful anhydride, successful anhydrides, and the Reactor Scheme.  Can anyone figure out what's going on here.

 

Thanks!

 

Ed

Ed, please attach the reaction scheme separately, as a single mrv file.  From EnumerationInfo.mrv I cannot tell what is the exact reaction.

Zsolt

Thanks for your prompt reply.  I've attached the reaction scheme separately.   The library I'm enumerating is essentially an amidation of a Boc Protected amino acid, followed by a deprotection then acylation of the primary amine. 

Thanks again.

 

Ed

There are 3 reactants in your reaction scheme; please attach them all. FailedAnhydride.mrv seems to be a correct 3rd reactant.

Zsolt

Do to the proprietary nature of my work here, I'm not comfortable is posting all of the reagents in a forum like this.  You're right, there are 3 reagents in this a reaction scheme, an N-Boc Amino acid, a primary amine, and the anhydride.  I've tried to create a very simple reactant scheme containing an amine, and an anhydride to  give the N-Acylated product, and the product shown in the file, "FailedAnhydride.mrv" still does not give any products to shows after enumeration, while the other anhydrides work fine.  It's very strange and I can see no reason why that one doesn't work. 

Thanks for your help.

Ed

Ed, we can reproduce the error. There's an internal search bug in Reactor, that's why it does not generate products when FailedAnhydride.mrv is the 3rd reactant. We will fix it ASAP, and notify you here when the fix will be available.

Zsolt

Unfortunately fixing this error is more complex than we thought. Reactor internally uses the general aromatized form of FailedAnhydride.mrv, which is "O=c1oc(=O)c2ccccc2c2ccccc12". In this form all three rings are aromatized, and they do not match to "O=COC=O", so the molecule is not accepted as 3rd reactant. Fixing this error requires more time, it will not be fixed in the next patch release.

Sorry for the inconvenienece.

Zsolt

Thanks for looking into this for me.  I kind of thought it might have to do with the smiles structure, but wasn't sure.  Originally we planned to use this anhydride in a library synthesis, but when we found we couldn't enumerate the products with it, we replaced it with a similar anhydride which could be enumerated. 

Thanks again.

Ed