purchased from Sigma–Aldrich–Fluka, 2–5a, 7a, 9–10a, 11a, 16a,
17a, 19a, 20a and 21a were supplied by Alfa Aesar, 13a, 22a,
23a and 24a were obtained from Acros Organics and compound
25a was a product by TCI Europe. All the starting indoles were
products from Sigma-Aldrich-Fluka, with the exception of 4-
chloroindole, which was purchased from Acros Organics. All other
reagents and solvents were of the highest quality grade available.
Chemical reactions were monitored by analytical TLC, per-
formed on silica gel 60 F254 plates and visualized by UV
irradiation. Flash chromatography was carried out with silica gel
60 (230–240 mesh). Kinetic parameters were measured in a Varian
Cary50Bio UV/Vis spectrophotometer. Melting points were taken
on samples in open capillary tubes and are uncorrected. IR
spectra were recorded on infrared spectrophotometer using KBr
General procedure for the PTDH-mFMO biocatalysed
sulfoxidations
Unless otherwise stated, prochiral sulfides 1–25a (5 mM) were
dissolved in a 50 mM Tris-HCl buffer pH 9.0 (1.0 mL) containing
1% DMSO, sodium phosphite (10 mM), NADPH (0.2 mM) and
the self-sufficient biocatalyst PTDH-mFMO (4 mM). Reactions
were stirred at 25 ◦C and 250 rpm for the times established.
Reactions were then stopped, extracted with EtOAc (2 ¥ 0.5 mL),
dried onto MgSO4 and analyzed by GC and/or HPLC in order
to determine the conversions and the enantiomeric excesses of
the sulfoxides (R)- or (S)-1–25b. Control reactions in absence of
biocatalyst were performed and did not result in any conversion.
1
pellets. H-NMR, 13C-NMR and DEPT spectra were recorded
Acknowledgements
with tetramethylsilane (TMS) as the internal standard with a DPX
(1H: 300.13 MHz; 13C: 75.5 MHz) spectrometer. The chemical shift
values (d) are given in ppm. Optical rotations were measured using
a polarimeter and are quoted in units of 10-1 deg cm2 g-1. APCI+
and ESI+ using a chromatograph mass detector or EI+ with a
mass spectrometer were used to record mass spectra (MS). High-
resolution mass spectra were obtained with a Bruker Microtof-Q-
spectrometer.
Marco W. Fraaije, Daniel E. Torres Pazmin˜o and Gonzalo
de Gonzalo thank the EU-FP7 Oxygreen project for financial
support. Ana Rioz-Mart
´ınez (FPU Program) thanks the Spanish
Ministerio de Ciencia e Innovaci
o´n (MICINN) for her predoctoral
fellowship which is financed by the European Social Fund.
Notes and references
Methyl phenylethyl sulfide 15a was synthesized by treating at
1 W. J. H. van Berkel, N. M. Kamerbeek and M. W. Fraaije, J. Biotechnol.,
2006, 124, 670.
0
◦C the corresponding thiol with sodium and methyl iodide
in dry MeOH, under a nitrogen atmosphere (40% yield).17 2-
(Methylthio)pyridine 18a was prepared by reaction of the cor-
responding thiol and potassium carbonate with iodomethane and
2 (a) A. Alfieri, E. Malito, R. Orru, M. W. Fraaije and A. Mattevi,
Proc. Natl. Acad. Sci. U. S. A., 2008, 105, 6572; (b) R. Orru, D. E.
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◦
triethylamine in CH2Cl2 at 0 C (99% yield).18 p-Acetoxyphenyl
methyl sulfide 2c was obtained from 2a by acetylation in presence
of acetic anhydride and pyridine (90% yield). Racemic sulfoxides
( )-1–15b, ( )-18–21b and ( )-23–24b were prepared by chemical
oxidation of the corresponding sulfides employing hydrogen per-
oxide and methanol (yields higher than 60%). All the synthesised
compounds 15a,19a 18a,18 1b,17 2b,19b 3–7b,17 8b,19c 9–15b,17 18b,19d
19b,19e 20b,19f 21b,19d 23b,19g 24b19d exhibited physical and spectral
data in agreement with those reported.
Absolute configurations of sulfoxides 1b,17 3–7b,17 9–15b,17
18b,20a 19b,20b 20b,20a 21b19e were determined by comparison of
elution order on HPLC with published data, meanwhile the
absolute configurations of sulfoxide 2b and 8b were established
by comparing the retention times on HPLC for acetylated 2b
and 8b with the ones obtained in the asymmetric sulfoxidations
of prochiral sulfides 2c and 8a employing (+)-diethyl L-tartrate,
Ti(O-i-Pr)4 and TBHP.21 The absolute configuration of compound
23b was obtained by comparing the specific rotation value with
published data,22 while absolute configuration of butyl ethyl
sulfoxide 24b was established by analogy with this latest one.
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Fischer and R. D. Schmid, Chem.–Eur. J., 2000, 6, 1531.
General procedure for the oxidation of indole and derivatives
employing PTDH-mFMO
A plate with 24 wells was employed. A solution of the corre-
sponding starting indoles (5.0 mM) was dissolved in Tris-HCl
buffer 50 mM, 35 mM NaCl, pH 8.5 containing sodium phosphite
(10 mM), NADPH (0.2 mM) and self-sufficient biocatalyst
◦
PTDH-mFMO (4 mM). Reactions were stirred at 25 C for 18 h
and products formation was observed colorimetrically.
1340 | Org. Biomol. Chem., 2011, 9, 1337–1341
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The Royal Society of Chemistry 2011
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