Bienzymatic Dynamic Kinetic Asymmetric Transformation
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References
(R)-Octopamine [(R)-1]
(R)-6 (800 mg, 5.4 mmol) was dissolved in dry THF (34 mL)
and LiAlH4 (307 mg, 8.1 mmol) was added, the mixture was
stirred at room temperature overnight. The ice-cooled reac-
tion mixture was quenched with Na2SO4 solution (saturated,
5 mL), the pHbrought to >10 and the precipitate filtered
off. The filtrate was evaporated and purified by column
chromatography with dichloromethane/methanol/25% aque-
ous NH3 in a ratio of 75/20/5 (v/v/v) as eluent to give solid
(R)-1; yield: 128 mg (16%). (R)- and (S)-1 were not separat-
ed on a Crownpackꢁ Cr (+) (150 mm, 5 mm) column and
thus, for ee determination a Chirosilꢁ RCA (+) crown ether
column was utilized under standard conditions [10 mM
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CH3COOHin water/CH CN with 10 mM CH3COOH=90/
3
10 (v/v%), 1.6 mL/min, 508C]; HPLC: t(R)-1 =7.3 min, t(S)-1
=
8.4 min; [a]2D0: À36.1 (c 0.56, H2O); lit.[29] [a]2D0: À37.6 (c 0.56,
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(S)-Octopamine [(S)-1]
4-Hydroxybenzaldehyde (0.977 g, 8.0 mmol) was dissolved
in DMSO (16 mL) and mixed with glycine (30 g, 0.4 mol) to-
gether with lTA (1400 U) and l-TyrDC (Efi1, 40 U) in cit-
rate/phosphate buffer pH6.0 (37 m M citric acid, 126 mM
Na2HPO4). The mixture was incubated in a 250 mL round-
bottom flask with stirring at room temperature. The reaction
mixture was acidified to pH1–2, and precipitated protein
was removed by centrifugation. After titration to pH3 an
ultrafiltration was applied (Amicon 8050 stirred cell, YM-10
membrane, Millipore). The ultrafiltrate was concentrated to
0.1 L under vacuum, acetone was added, and the mixture
was stored at À208C for 1 h. Precipitated glycine was fil-
tered off, and the filtrate was concentrated to a volume of
40 mL. After adjusting to pH10.5 with aqueous NaOH
(30%), the solution was evaporated leaving a liquid residue
that was treated with ethyl acetate. Precipitated solids were
filtered off, and the filtrate was evaporated under vacuum.
The remaining liquid was purified by column chromatogra-
phy with dichloromethane/methanol/25% aqueous NH3 in a
ratio of 75/20/5 (v/v/v) as eluent to give solid (S)-1; yield:
574 mg (47%); [a]D20: +27.7 (c 0.55, H2O); for (R)-1: lit.[29]
[a]20: À37.6 (c 0.56, H2O). This corresponds to an ee of 74%
forD(S)-1, which is in agreement with the ee value deter-
mined by chiral HPLC analysis of 81%. NMR data were
consistent with those reported.[29]
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Acknowledgements
The Österreichische Forschungsfçrderungsgesellschaft (FFG),
the Province of Styria, the Styrian Business Promotion
Agency (SFG), the city of Graz, the Fonds zur Fçrderung
der wissenschaftlichen Forschung (FWF, project W901-B05
DK Molecular Enzymology) and the European Commission
within the framework of a Marie-Curie Industrial Host Fel-
lowship to Martin Schürmann and Michael Wolberg are ac-
knowledged for financial support. We would like to thank
Marcel Wubbolts, Theo Sonke and Kurt Faber for stimulating
discussions.
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Acids Res. 1994, 22, 4673.
Adv. Synth. Catal. 2007, 349, 1379 – 1386
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