Hi,
I would like to use Depsidipeptide units in the synthesis of my peptide (~50 aa) which is commonly coupled sequentially under microwave conditions at 90 °C (CEM Liberty Blue) in order to generate photo-triggered "click-peptides". Is the ester bond stable at these high temperaturatures? From the mass spectra of my first approach there seems to be complete diketopiperazine formation during Fmoc-deprotection of the following amino acid. Will it be sufficient to do this deprotection step at room temperature or should I change my strategy to the use of TBAF for cleaveage or the Bsmoc protecting group?
Thanks a lot for your advice.
Matthias
Dear Mathias,
The group reactivity depends on many factors, as you already know as a good chemist (the question confirms that!). Esters are not that heat-labile in general but the medium (hope its neutral or very near neutral ) helps to keep the ester intact) plays role(s) in hydrolysis followed by cyclization etc. which are prone to happen. I guess, you will be right in approaching the reaction at RT (Room Temperature) before you opt the other deprotecting reagent which can follow after the confirmations have been earned from the low-temp/RT reaction. I would suggest trying the reaction on a model, low scale first. Hope these are fruitful. Thanks for sharing your question and giving an opportunity to share my thoughts on this. Seems Chemists are a bit more self-critical (including myself)! Thanks again!
I synthesized the following test-sequence: H2N-IIISer(Ala)-TIGGIFG-OH.
I introduced the depsi-dipeptide unit and the next Ile-res at 50 °C and deprotected both with 20% piperidine (5+10 min) at room temperature. The deprotection of the second and third Ile-res and the coupling of the third Ile res were performed at 90 °C. Mass analysis as well as HPLC-chromatography showed a relatively clean product with an Ile-deletion which is probably correlated to the last coupling.
Therefore, it seems sufficient to perform the Fmoc-Deprotection at room temperature to prevent DKP-formation (in this case) and the ester-bond seems to be stable against high temperatures in microwave assisted SPPS.
- Badges
- Science topic
- Similar topics
- Physical Sciences
- Physical Phenomena
- Luminescence
- Fluorescence