I got an amino acid salicyl aldehyde ester attached through N Boc protected oxazolidine ring, to a Ser derivatized resin and I want to cleave the oxazolidine keeping the ester linkage.
Could anyone suggest the percentage of water/tfa to use for this scope?
The classical methods leading to aldehyde from oxazolidines derivatives, involve the use of TFA/water 10:5 in presence of excess of methanol and DCM, which in my case would be risky in that the methanol could cause transesterification.
On the other hand I am not sure if such high percentage of water would cause acidic hydrolysis of the ester bond which I MUST preserve.
Other protocols suggest to hydrolyze the oxazolidine ring with 0.1% TFA in MeCN:water at 60 degrees for 3h. Does anybody have any suggestion? Thank you for the interest.
One can try hydrolysis of oxazolidine ring using resin Amberlyst-15.
Dear dr Madhukar Baburao Deshmukh thank you for your answer.
I have my peptide OXazolidine onto resin, to be therefore delivered after the ring breaking reaction, as aldehyde....would you suggest any protocol in compliance to your suggestion?
Hello,
I am not sure to have undertood very weel the structure of your molecule, but I can say that I synthesize peptides on resin (chlorotrityl) and I proceed to the cleavage with 1% TFA in DCM. It's sufficient, and groups like Boc, wich is an ester function, are not affected. But maybe it can be considered as a stable ester.. Anyway, I think that those conditions could be ok for you. But I can't guarantee.
Didn't Evans cleave an oxazolidinone with hydrogen peroxide and LiOH?
Dear Fabien Thoreau I need to have my peptide on Tfa stable resin, which for the specific case is the merrifield. The C terminal is an phenyl oxazoline ester (COO-Ph-NO-Serine-spacer-resin) which I want to hydrolize to get the corresponding aldehyde still preserving the ester on the other side of the functional group.
Dear Mitchell I cannot use such reagent since it would surely cause the breaking of the phenyl ester bond.
Dear Philippe Roger Bovy, thank you for the interest in this topic.
I cannot go for your suggestion since the methylation would favour the unwanted rearrangement of the oxazolidine ring, via nucleophilic attack of the nitrogen onto the adjacent ester bond to the first residue..
Yes, a phenyl ester is pretty labile, but we have had luck with Evans' conditions with a benzyl ester of a benzoate on the same molecule as the oxazolidinone ring, which we also considered rather weak. The key is to generate completely the LiOOH before introducing the oxazolidinone. Might be worth a try on small scale or with a model phenyl ester.
Dear Mitchell A deLon thank you for your answer.
I do not know such reaction, could you please provide more details with some references?
Regards
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