Organic Process Research & Development
Communication
Determination of Oxidation Reaction Using Fenton’s
Reagent. Twenty mg of rifamycin B (0.026 mmol) were
dissolved in 9.5 mL of KPi buffer (10 mM, pH 8) containing
(3) Sensi, P.; Maggi, N.; Ballotta, R.; Fu
J. Med. Chem. 1964, 7, 596−602.
̈
res
́
z, S.; Pallanza, R.; Arioli, V.
(
(
(
4) Wehrli, W. Clin. Infect. Dis. 1983, 5, 407−411.
5) Prelog, V.; Oppolzer, W. Helv. Chim. Acta 1973, 56, 2279−2287.
0
.5 mL of methanol and 0.6 mL of H O (0.15% m/v). The
2 2
6) Aristoff, P. A.; Garcia, G. A.; Kirchhoff, P. D.; Showalter, H. D.
reaction was performed in presence and absence of 0.5 mL of
.54 mM FeSO solution (final concentration 0.027 mM) and
Tuberculosis 2010, 90, 94−118.
7) Bakker, M. I.; Hatta, M.; Kwenang, A.; Van Benthem, B. H. B.;
Van Beers, S. M.; Klatser, P. R.; Oskam, L. Am. J. Trop. Med. Hyg.
005, 72, 443−448.
(8) Muller, P.; Alber, D. G.; Turnbull, L.; Schlothauer, R. C.; Carter,
0
4
(
was analyzed by LC/MS after 30, 60, 120, and 180 min (see
Figure S1, SI).
2
Determination of the Oxidation Reaction Using APS.
Twenty mg of rifamycin B (0.026 mmol) were dissolved in 10
mL of KPi buffer (10 mM, pH 8) containing 0.5 mL of
methanol. Then 6 mg of APS (0.026 mmol) were added. The
reaction was analyzed by LC/MS after 30, 60, 120, and 180 min
̈
D. A.; Whitchurch, C. B.; Harry, E. J. PLoS One 2013, 8, e57679.
(9) Granoff, D. M.; Daum, R. S. J. Pediatr. 1980, 97, 854−860.
(
́
10) Havlir, D. V.; Dube, M. P.; Sattler, F. R.; Forthal, D. N.;
Kemper, C. A.; Dunne, M. W.; Parenti, D. M.; Lavelle, J. P.; White, A.
C.; Witt, M. D.; Bozzette, S. A.; McCutchan, J. A. N. Engl. J. Med.
(
see Figure S2, SI).
Minimal Methanol Content (Process 1). Thirty mg of
1
(
(
996, 335, 392−398.
11) Floss, H. G.; Yu, T.-W. Chem. Rev. 2005, 105, 621−632.
Rifamycin B (0.039 mmol) were dissolved in different amounts
of methanol (see Figure S6, SI). The obtained solutions were
mixed with 9 mg of APS (0.039 mmol) and 5 mL of KPi buffer
12) Sensi, P.; Margalith, P.; Timbal, H. R. Farmaco. Sci. 1959, 14,
1
(
46−147.
13) Pasqualucci, C. R.; Bonfanti, G.; Turolla, C. A Method of
(
10 mM, pH 9.5). The mixtures were stirred at 60 °C for 4 h.
Producing Rifamycin O from Fermentation Broths. Patent
GB1381992, 1975.
Then 500 μL of sample were extracted with 500 μL of ethyl
acetate and analyzed by LC/MS. In the experimental setup with
(14) Pasqualucci, C. R.; Bonfanti, G.; Scarpitta, G. A Process for
Preparing Rifamycin S by Hydrolysis of Rifamycin O. Patent
GB1431034, 1976.
3
mL of MeOH (5 mM final concentration of rifamycin B) 3.5
mM rifamycin S were obtained (70% yield).
(
15) Jin, Z. H.; Lin, J. P.; Xu, Z. N.; Cen, P. L. J. Gen. Appl. Microbiol.
002, 48, 329−334.
16) Ghisalba, O.; Nu
17) Venkateswarlu, G.; Murali Krishna, P. S.; Venkateswar Rao, L.
Bioprocess Eng. 1999, 20, 27−30.
18) Nachega, J. B.; Rosenkranz, B.; Simon, G.; Chaisson, R. E.;
High Methanol Content (Process 2). Forty mg of rifamycin
B (0.052 mmol) and 12 mg of APS (0.052 mmol) were added
to 400 μL of MeOH and 4 μL of KPi buffer (10 mM, pH 9.5,
2
(
(
̈
esch, J. J. Antibiot. 1978, 31, 215−225.
1
°
% v/v). The obtained suspension was heated for 20 min at 60
C. Then 40 μL of the sample were quenched with 100 μL of
KPi buffer (pH 9.5, 10 mM) and analyzed by LC/MS. 89.8 mM
(
Diacon, A. H.; Taljaard, J. Infect. Disord. Drug Targets 2011, 11, 134−
143.
(68% yield) rifamycin S were obtained (see Figure S8, SI).
Rifamycin B Oxidation in Absolute Methanol under
(19) Prat, D.; Pardigon, O.; Flemming, H.-W.; Letestu, S.; Ducandas,
V.; Isnard, P.; Guntrum, E.; Senac, T.; Ruisseau, S.; Cruciani, P.;
Hosek, P. Org. Process Res. Dev. 2013, 17, 1517−1525.
Argon Atmosphere. Forty mg of rifamycin B (0.052 mmol)
and 12 mg of APS (0.052 mmol) were added under argon
atmosphere to 400 μL of absolute MeOH (dried with CaH2).
The obtained suspension was heated for 20 min at 60 °C. Then
0 μL of the sample were quenched with 100 μL of KPi buffer
pH 9.5, 10 mM) and analyzed by LC/MS.
(
20) Jin, H. Z.; Lin, J. P.; Xu, Z. N.; Cen, P. L. J. Gen. Appl. Microbiol.
2
002, 48, 329−334.
21) Han, M. H.; Seong, B.-L.; Son, H.-J.; Mheen, T.-I. FEBS Lett.
983, 151, 36−40.
(
1
4
(
Reaction in Pure Solvent with Different Concen-
trations and Solvent Systems. Forty mg of rifamycin B
(
0.052 mmol) and 12 mg of APS (0.052 mmol) were added to
00−1000 μL MeOH as well as to 1000 μL of acetonitrile,
4
DMSO, ethanol, or isopropyl alcohol. The mixtures were
shaken for 10 min at 70 °C and analyzed by LC/MS (see
Figure S9, SI).
ASSOCIATED CONTENT
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*
S
Supporting Information
AUTHOR INFORMATION
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*
Notes
The authors declare no competing financial interest.
REFERENCES
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(
2
1) Burman, W. J.; Gallicano, K.; Peloquin, C. Clin. Pharmacokinet.
001, 40, 327−341.
2) Margalith, P.; Pagani, H. Appl. Environ. Microbiol. 1961, 9, 325−
(
3
34.
D
Org. Process Res. Dev. XXXX, XXX, XXX−XXX