Each cycle would be done with 2 treatments, 1 min each. Topic is phenyl esters hydrolysis.
In my opinion under DBU/HOBT conditions phenyl ester going to be very stable for the hydrolysis. Even if there is a plenty of moisture still phenyl ester going to be retained in the FMoc removal cycle
Generally bulkier protecting groups tend to be used, t-butyl, or phenylisopropyl which are only particularly labile in acid. However with DBU/HOBT the only nucleophiles about will be adventitious water and HOBT so it should be fine.
Do you need to retain the phenyl ester on resin cleavage?
Thank you for your answers.
Dear Eric
The final product is a C terminal aldehyde generated via acidic hydrolysis of the corresponding oxazolidine, but for that i do expect the phenyl ester to be stable under Tfa cleavage conditions.
My concern is whether the phenolic ester is stable under the fmoc depo steps, with DBU.
Over the past week i read an article where my concern found confirmation, though in such paper they didn't use HOBT, which i think to be able to prevent the unwanted hydrolysis due to its acidic character.
Thank you for the clarification. DBU/HOBT should be fine at the relative concentrations you have listed. The phenyl ester itself is not inherently base labile and requires a nucleophile for transesterification, I would not expect HOBT to transesterify even under repeated exposure, however water could potentially be a problem.
TBAF could be a viable alternative and has literature precedence in Fmoc SPPS. It would be less basic but water would be more of an issue.
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