Dear everyone,
I'm looking for a cleavage method for Fm-Thioesters (S-9-Fluorenylmethyl) which doesn't cleave disulfide bonds at the same time. My compound is a peptide, so I'm mostly working in aqueous solution or DMF, acetonitrile etc.
I've already tried Piperidine/DMF in various concentrations, but it always cleaves the disulfides within the first 5 min. Furthermore, I've tried using NaOH and tert-butyl-tetramethylguanidine. But all with the same results...
If you know of any methods, please let me know :-)
Thanks a lot,
Christina
@Christina
Have you tried a bulkier amine base such as DBU? See p. S8 (Compound S5 to Compound 9) in the Supporting Information below from an Org. Lett. publication by the Garner Group at Washington State U in the USA:
"Rapid Formation of N-Glycopeptides via Cu(II)-Promoted Glycosylative Ligation"
http://pubs.acs.org/doi/suppl/10.1021/ol302961s/suppl_file/ol302961s_si_001.pdf
Original Article:
http://pubs.acs.org/doi/abs/10.1021/ol302961s
Your target compound may be inherently unstable. Once the Fm-thioester has been deprotected, the sulfur of the thioacid may react intra- or inter-molecularly with the disulfide, scrambling the disulfide or initiating disulfide oligomerization during HPLC purification. Perhaps the bulky DBU can form a strong ion pair with the resulting thioacid and sterically hinder any reaction with the disulfide. I am not sure if your target compound can withstand prolonged storage without further oxidation or hydrolysis of the thioester.
Hope this helps.
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