I'm sorry for having sent the message below in HTML format which is not
compatible with many mailing programs. Igor
---------------------------------------------------
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
This archive was generated by hypermail 2b29 : Mon Jun 12 2000 - 13:09:42 EDT