Dear Hanno:
Few years ago we tried to reproduce the high-yield mono-oxidation of Met suspended in acetic acid with 1.2 equivalents of H2O2 according to Iselin, B. [Helv.Chim.Acta 1961, 44, 61-79], and failed. It looked like all H2O2 was consumed under these conditions, since unacceptable amounts of sulfone were invariably co-produced. However, very clean selective monooxidation was observed when homogeneous solution of Boc-Met-OH in acetic acid was treated with 1 equivalent of H2O2 "exactly" (i.e. slightly less than 1 equiv; obtained without correction for decomposition). The selectivity problem seemed to be related to inaccurate estimation of this oxidant concentration in solution (who wants titrate every time...?). Precise measuring of hydrogen peroxide would be possible in case of its stable synthetic equivalents like H2O2-urea adduct or peroxyacid salts like Na2S2O8, NaBO3. As far as I know, only the latter was studied among the other oxidants by Yajima et al [Chem.Pharm.Bull.Jpn. 1978, 26(2), 650-3], but again, it was applied in 20-30% excess with respect to Met. The best mono-oxidation yields reported were about 80%[=100-20]%.
I like the proposal of Anders H. Johnsen, but I'm afraid that auto-oxidation proceeds spontaneously and in high yield when unwanted only (:-)). So, I recommend to add a sub-equivalent amount of H2O2.
Other 'Met(O)-specific tips' I learned from my limited experience:
i. Under standard AAA conditions Met(O) is largely reverted to Met (see Barany&Merrifield review in Peptides vol.2)
ii. For long peptides HPLC may not resolve Met/Met(O)-forms
iii. For small peptides HPLC may resolve diastereomeric d,l-sulphoxides [extra chiral -S*(O)-].
Good luck!
Igor Rodionov
Laboratory of Peptide Chemistry
Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry
6 Science Avenue, Pushchino, Moscow Region
142292, Russian Federation
rodionov@fibkh.serpukhov.su
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