Tetrahedron Letters
CO2-expanded liquids as solvents to enhance activity of Pseudozyma
antarctica lipase B towards ortho-substituted 1-phenylethanols
Moeko Otsu a, Yuichi Suzuki a, Afifa Ayu Koesoema a, Hai Nam Hoang b, Mayumi Tamura a,
Tomoko Matsuda a,
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a Department of Life Sciences and Technology, School of Life Science and Technology, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan
b Faculty of Chemical Engineering, University of Technology, Vietnam National University of Ho Chi Minh City, 268 Ly Thuong Kiet, District 10, Ho Chi Minh City 740030, Viet Nam
a r t i c l e i n f o
a b s t r a c t
Pseudozyma (Candida) antarctica lipase B (CAL-B, Novozym 435Ò) is one of the most widely used and out-
standing biocatalysts. However, CAL-B-catalyzed transesterification of ortho-substituted 1-phenylethanol
analogs suffers low conversion. In this research, the reactions were accelerated by using CO2-expanded
liquids, liquids expanded by dissolving pressurized CO2, such as CO2-expanded hexane or CO2-expanded
MeTHF.
Article history:
Received 23 March 2020
Revised 23 August 2020
Accepted 28 August 2020
Available online 5 September 2020
Ó 2020 Elsevier Ltd. All rights reserved.
Keywords:
CO2-expanded liquid
Lipase
Ortho-substituted 1-phenylethanol
Bio-based liquid
Introduction
should be chosen since they have been generating a massive
amount of waste and burden both economically and environmen-
Biocatalysts, especially lipases, have been studied extensively
[1,2]. Among them, Pseudozyma (Candida) antarctica lipase B
(CAL-B, Novozym 435Ò) is one of the most widely used and out-
standing biocatalysts; CAL-B catalyzes transesterification of a wide
range of secondary alcohols in organic solvents smoothly with
excellent enantioselectivity [3–7]. However, CAL-B-catalyzed
transesterification of ortho-substituted 1-phenylethanol analogs
suffers much lower conversions than those of meta and para- sub-
tally [18,19]. Therefore, methods for minimizing the usage of sol-
vents and replacing traditional organic solvents by
environmentally friendly alternatives have been studied exten-
sively [20–22]. As sustainable solvents, CO2 related solvents such
as supercritical CO2 (scCO2), liquid CO2 and CO2-expanded liquids
have attracted great attentions [23–27]. Among them, CO2-
expanded liquids, liquids expanded by dissolving CO2, have an
advantage over scCO2 and liquid CO2; CO2-expanded liquids can
be used under lower pressures with wider temperature ranges
than scCO2 and liquid CO2 [23]. As a liquid to be expanded by
CO2, it is desirable to use bio-based solvents such as 2-methylte-
trahydrofuran (MeTHF), which can be derived from lignocellulosic
biomass and has recently gained increasing interests as a promis-
ing solvent for various synthesis applications [28–30], including
biocatalysis [31].
Previously, we have reported the utilization of CO2-expanded
bio-based liquids as effective reaction media for transesterification
of alcohols catalyzed by CAL-B [27,32,33]. As shown in Fig. 1, the
reaction is accelerated especially for 1-(20-bromophenyl)ethanol
using CO2-expanded MeTHF. However, ortho-substituted 1-pheny-
lethanol analogs, except 1-(20-bromophenyl)ethanol, have not
been used as substrates although these compounds are important
as chiral intermediates for pharmaceuticals [34–38]. To assess the
effectiveness of CO2-expanded liquids for biocatalysis further, in
this study, we investigated CAL-B-catalyzed transesterification of
stituted analogs (Supplementary information Section
2 and
Table S1). Due to the limitation of the substrate scope of CAL-B,
the dynamic kinetic resolution of ortho-substituted 1-phenyletha-
nols also resulted in considerable retardations in the reactivity [7].
For example, reaction of 1-(20-bromophenyl)ethanol took 7 days to
complete whereas that of 1-phenylethanol took 3 h. The lipase-cat-
alyzed resolution reaction became rate-limiting in the overall reac-
tions. It was also reported that reactivities of Burkholderia
(Pseudomonas) cepacia lipase for transesterification of ortho-substi-
tuted 1-phenylethanol analogs were extremely lower than those of
meta- and para-substituted analogs [8].
The limitation of biocatalysts has been overcome by mutations
and chemical modifications of enzymes and solvent engineering
[1,9–17]. For solvent engineering, sustainable solvents should be
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Corresponding author.
0040-4039/Ó 2020 Elsevier Ltd. All rights reserved.