Organic Process Research & Development
Article
amines. Efforts have been focused on the optimization of the
scale-up of the biocatalytic transamination and the substrate
concentration; thus, taking into account other TA-catalyzed
protocols, the transformations were successfully carried out at
higher concentrations between 100 and 250 mM (14−50 g/L),
affording in all cases the enantiopure amines with high isolated
yields. Thus, this optimization study clearly offers a new
advantageous alternative in terms of production and economic
issues towards derivatives which are not easily accessible.
ASSOCIATED CONTENT
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S
* Supporting Information
Experimental procedures for the chemical synthesis of racemic
amines and the biocatalytic transamination experiments, full
characterization of novel compounds, spectroscopic and
analytical data of the enantioenriched final products. This
material is available free of charge via the Internet at http://
AUTHOR INFORMATION
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EXPERIMENTAL SECTION
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Corresponding Authors
General. Ketones 1a−p and amines 2a,d,m−o were
purchased from commercial sources and used as received.
Codex Transaminase Screening Kit (ATASK-000250), PLP,
lactate dehydrogenase, and glucose dehydrogenase present in
the PRM-102 mix were purchased from Codexis. All other
reagents and solvents were of the highest purity available.
Chemical reactions were monitored by analytical TLC,
performed on silica gel 60 F254 plates, and visualized by UV.
Flash chromatography was performed using silica gel 60 (230−
400 mesh). IR spectra were recorded on an infrared Fourier
transform spectrophotometer on NaCl pellets. NMR spectra
were recorded at 300 (1H), and 75 (13C) MHz. The chemical
shifts (δ) are reported in parts per million (ppm) relative to the
solvent residual signals and the coupling constants (J) in Hertz
(Hz). ESI-TOF mode was used to record high-resolution mass
spectra (HRMS). Gas chromatography (GC) analyses were
performed on a standard gas chromatograph equipped with a
FID. HPLC analyses were performed using a standard HPLC
chromatograph with UV detection. Optical rotations were
measured using a standard polarimeter with a sodium lamp (D)
and are reported in units of 10−1 deg cm2 g−1.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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I.L. thanks the Spanish Ministerio de Ciencia e Innovacion
(MICINN) for personal funding (Ramon
́
́
y Cajal Program).
Financial support of this work by the Spanish MICINN
(Project MICINN-12-CTQ2011-24237) is gratefully acknowl-
edged. This work was supported by Eli Lilly and Company
through the Lilly Research Award Program (LRAP).
REFERENCES
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dx.doi.org/10.1021/op4003104 | Org. Process Res. Dev. XXXX, XXX, XXX−XXX