ENANTIOMER PURIFICATION THROUGH ACHIRAL CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED AND SELF-DISPROPORTIONATION OF ENANTIOMERS
Enantiomer purification is a critical process in the pharmaceutical, agrochemical, and food industries, where chiral compounds often exhibit distinct biological activities. Traditional chiral chromatography is effective but costly due to the use of expensive chiral stationary phases. This review art...
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| author | Wzorek, Alicja Klika, Karel Han, Jianlin Sorochinsky, Alexander Ono, Taizo Soloshonok, Vadim |
| author_facet | Wzorek, Alicja Klika, Karel Han, Jianlin Sorochinsky, Alexander Ono, Taizo Soloshonok, Vadim |
| author_institution_txt_mv | [
{
"author": "Alicja Wzorek",
"institution": "Institute of Chemistry, Jan Kochanowski University in Kielce, Uniwersytecka 7, 25-406 Kielce, Poland"
},
{
"author": "Karel Klika",
"institution": "Molecular Structure Analysis, German Cancer Research Center (DKFZ), ImNeuenheimer Feld 280, 69120 Heidelberg, Germany"
},
{
"author": "Jianlin Han",
"institution": "Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China"
},
{
"author": "Alexander Sorochinsky",
"institution": "Department of Fine Organic Synthesis, V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, The National Academy of Sciences of Ukraine, 1 Murmanska str., Kyiv 02094, Ukraine"
},
{
"author": "Taizo Ono",
"institution": "National Institute of Advanced Industrial Science and Technology, 463-8560, Nagoya, Japan"
},
{
"author": "Vadim Soloshonok",
"institution": "University of Basque Country"
}
] |
| author_sort | Wzorek, Alicja |
| baseUrl_str | https://ucj.org.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-22T08:23:55Z |
| description | Enantiomer purification is a critical process in the pharmaceutical, agrochemical, and food industries, where chiral compounds often exhibit distinct biological activities. Traditional chiral chromatography is effective but costly due to the use of expensive chiral stationary phases. This review article highlights a recent breakthrough in enantiomer purification under entirely achiral conditions. Specifically, it focuses on the convergence of achiral simulated moving bed chromatography and the phenomenon of self-disproportionation of enantiomers (SDE). Experimental validation using scalemic methyl p-tolyl sulfoxide as a model compound enabled the isolation of the excess enantiomer with high purity (99% ee) and a respectable yield (~50%). This innovative process features exceptional productivity (up to 99 grams per liter of column volume per day), reproducibility, and reliability. This breakthrough presents the first practical example of enantiomer purification based on SDE, offering a scalable and economically viable alternative to conventional chiral separations. Given that SDE is an inherent property of all chiral compounds, this innovative approach is anticipated to become the method of choice for practical enantiomer purification in both research and industrial production. |
| doi_str_mv | 10.33609/2708-129X.91.3.2025.34-48 |
| first_indexed | 2025-09-24T17:44:00Z |
| format | Article |
| fulltext |
34 ISSN 2708-129X. Укр. хім. журн., 2025
UDC 546.26-162: 541.13:549.21 doi: 10.33609/2708-129X.91.3.2025.34-48
ENANTIOMER PURIFICATION THROUGH ACHIRAL
CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED
AND SELF-DISPROPORTIONATION OF ENANTIOMERS.
Alicja Wzorek,1 Karel D. Klika,2 Jianlin Han,3 Alexander E. Sorochinsky,4
Taizo Ono,5 Vadim A. Soloshonok *6,7
1 Institute of Chemistry, Jan Kochanowski University in Kielce, Uniwersytecka 7, 25–406 Kielce, Poland;
2 Research and Development Center, Archer Daniels Midland, 1001 N Brush College Rd., Decatur,
IL 62521, USA;
3Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of
Chemical Engineering, Nanjing Forestry University, Nanjing 210037, China;
4 V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, The National Academy of Sciences
of Ukraine, Kyiv 02094, Ukraine;
5 National Institute of Advanced Industrial Science and Technology (AIST), 2266–98, Anagahora,
Shimoshidami, Moriyama-ku, Nagoya, 463–8560, Japan;
6 Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/
EHU, Paseo Manuel Lardizábal 3, 20018 San Sebastián, Spain;
7 IKERBASQUE, Basque Foundation for Science, María Díaz de Haro 3, Plaza Bizkaia, 48013 Bilbao,
Spain
*email: vadimsoloshonok@gmail.com
Enantiomer purification is a critical process in the pharmaceutical, agrochemical, and food
industries, where chiral compounds often exhibit distinct biological activities. Traditional chiral
chromatography is effective but costly due to the use of expensive chiral stationary phases. This
review article highlights a recent breakthrough in enantiomer purification under entirely achiral
conditions. Specifically, it focuses on the convergence of achiral simulated moving bed chroma-
tography and the phenomenon of self-disproportionation of enantiomers (SDE). Experimental
validation using scalemic methyl p-tolyl sulfoxide as a model compound enabled the isolation of
the excess enantiomer with high purity (∼99% ee) and a respectable yield (~50%). This innovative
process features exceptional productivity (up to 99 grams per liter of column volume per day), re-
producibility, and reliability. This breakthrough presents the first practical example of enantiomer
purification based on SDE, offering a scalable and economically viable alternative to conventional
chiral separations. Given that SDE is an inherent property of all chiral compounds, this innovative
approach is anticipated to become the method of choice for practical enantiomer purification in
both research and industrial production.
Key words: Chirality, Enantiomers, Purification, Self-Disproportionation of Enantiomers
(SDE), Achiral Chromatography, Simulated Moving Bed Chromatography.
35https://ucj.org.ua
Alicja Wzorek, Karel D. Klika, Jianlin Han, Alexander E. Sorochinsky, Taizo Ono, Vadim A. Soloshonok UCJ № 3 / Vol. 91
INTRODUCTION. Chiral compounds play
a crucial role in the pharmaceutical, agro-
chemical, and food industries [1–6]. Incor-
porating elements of chirality, particularly a
stereogenic carbon, in compounds under de-
velopment enhances the success rate of these
molecules as they progress from the discovery
phase to approval [7]. Approximately 70% of
approved drugs on the pharmaceutical market
contain at least one element of chirality [8].
Following the Thalidomide tragedy [9–11],
the FDA mandates a separate full biological
study for each enantiomer of submitted chiral
compounds. Asymmetric synthesis, whether
stoichiometric, catalytic, or enzymatic, very
rarely affords chiral compounds with the level
of enantiomeric purity required for the FDA-
mandated biological study [12]. Incredibly, the
final enantiomer purification stage can be the
most laborious and costly phase of the entire
chemical procedure [13, 14]. Therefore, the
ability to isolate pure enantiomers becomes an
absolutely essential part of successful drug de-
velopment, ensuring reasonable time and cost
structures.
Traditional enantiomer separation techni
ques, such as chiral chromatography (CCh)
and diastereoisomeric crystallization, grapple
with challenges like high costs and the unpre-
dictably complex selection of resolving agents
and conditions [15–18]. However, a recent
study led by Professor Dorota Antos [19] has
achieved a significant breakthrough by mer
ging two previously orthogonal innovations
in the fields of chirality and chromatographic
separations.
The first innovation is the self-dispropor-
tionation of enantiomers (SDE) [20, 21], which
allows for the separation of excess enantiom-
ers from the racemic portion under complete-
ly achiral conditions. The second is simulated
moving bed (SMB) chromatography, current-
ly the most efficient solution for continuous
chromatographic separation [2, 23].
This newly reported approach – achiral
SMB (ACh-SMB) – undoubtedly deserves spe-
cial attention and widespread dissemination
among practitioners in the areas of chirality,
chromatography, asymmetric synthesis, and
drug development in academic and industrial
research institutions. Given the high methodo-
logical and practical potential of these results,
this brief Perspective aims to highlight the
reported methodological and technological
advances, situating them within the greater
concept of the SDE phenomenon. These recent
developments bode well for the future general
applications of ACh-SMB-SDE as an approach
of choice in enantiomer purifications.
Self-disproportionation of enantiomers
(SDE). As illustrated in Fig. 1, a scalemic mix-
ture of 6 red and 3 blue enantiomers can adopt
five general configurations based on intermo-
lecular interactions. In configuration A, where
such interactions are absent or very weak, all
nine molecules in an achiral environment will
behave congruently, requiring a chiral selector
to distinguish between red and blue enantio
mers. However, when intermolecular interac-
tions occur, describing a scalemic compound
merely as a mixture of enantiomers becomes
conceptually incorrect and methodologically
misleading. Thus, if there is a preference for
heterochiral interactions, the sample should
be described as a collection of dimers (B) or
oligomers (E) along with the corresponding
monomers. Conversely, if homochiral inter-
molecular interactions dominate, the mole
cular configurations will include dimers versus
monomers (C) and a mixture of oligomers (D)
36 ISSN 2708-129X. Укр. хім. журн., 2025
ENANTIOMER PURIFICATION THROUGH ACHIRAL CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED
AND SELF-DISPROPORTIONATION OF ENANTIOMERS.ORGANIC CHEMISTRY
with molecular weight distributions reflecting
the ratio of the original enantiomers. These
four molecular configurations, driven by in-
termolecular interactions, are essentially mix-
tures of compounds with different molecular
weights and distinct physicochemical proper-
ties, resulting in their separation in a complete-
ly achiral environment. This spontaneous sepa
ration of scalemic samples into fractions with
proportions of enantiomers different from the
original mixture is termed Self-Disproportio
nation of Enantiomers (SDE) [24–26].
Fig. 1. Scalemic mixture of 33.33% ee and four
general configurations: absence of any intermole
cular interactions (A); intermolecular interactions
leading to the formation of heterochiral dimers
(B), homochiral dimers (C), homochiral oligomers
(D), and heterochiral oligomers (E).
Since intermolecular interactions are an in-
herent property of all chemical compounds,
one can deduce that SDE is similarly an in-
herent property of all chiral compounds. Sys-
tematic research into SDE began only about
20 years ago, generating a wealth of SDE data
for compounds of various chemical structures
and all common types of chirality, including
helical [27], axial [28–34] chirality, central
chirality on carbon [35–37], sulfur [38–41], as
well as compounds possessing multiple stereo
genic centers and C2 symmetry [42]. A simi-
lar wide generality is also reported for areas of
SDE manifestation, particularly in crystalliza-
tion [43, 44], sublimation [45–48], distillation
[49–51], density gradient ultracentrifugation
[52] or suspension precipitation [53], and chro-
matography – including simple gravity-driven
columns [54–56], flash chromatography [38],
MPLC [57–59], HPLC [28], size-exclusion
[51], and even gas chromatography [60].
Among the wider implications of the ubi
quitous nature of SDE is the problem of ac-
curately reporting the enantiomeric purity of
chiral compounds isolated from natural sour
ces or prepared in the laboratory [61–63]. SDE
is highly relevant to the field of chirality and
asymmetric synthesis. Understanding SDE
is crucial for accurately reporting the stereo-
chemical outcomes of enantioselective reac-
tions. SDE presents both a challenge and an
opportunity in chemistry, requiring careful
consideration and control to avoid errors in ex-
perimental results and interpretation [64–66].
A particularly exciting implication of SDE is
related to the origin of prebiotic homochirality.
Among various theories proposed, SDE is the
only experimentally proven mechanism for the
formation and maintenance of enantiomeri-
cally pure or highly enriched samples [67–69].
SDE and enantiomer purifications. In es-
sence, the SDE phenomenon is the spontane-
ous separation of the excess enantiomer from
the racemic portion. Therefore, enantiom-
er purification is an innate property and the
way of SDE manifestation. Thus, the primary
question is how to amplify this spontaneous,
innate enantiomer purification to a practical
application level. Research conducted on nu-
merous chiral compounds has identified cer-
tain structural classes and functional groups,
known as SE-phoric groups [21, 70], that allow
for high magnitudes of SDE, reaching prac-
B
C
D
A
E
Fig. 1. Scalemic mixture of 33.33% ee and four general configurations: absence of any intermolecular
interactions (A); intermolecular interactions leading to the formation of heterochiral dimers (B),
homochiral dimers (C), homochiral oligomers (D), and heterochiral oligomers (E).
Since intermolecular interactions are an inherent property of all chemical compounds,
one can deduce that SDE is similarly an inherent property of all chiral compounds. Systematic
research into SDE began only about 20 years ago, generating a wealth of SDE data for
compounds of various chemical structures and all common types of chirality, including helical
[27], axial [28–34] chirality, central chirality on carbon [35–37], sulfur [38–41], as well as
compounds possessing multiple stereogenic centers and C2 symmetry [42]. A similar wide
generality is also reported for areas of SDE manifestation, particularly in crystallization [43, 44],
sublimation [45–48], distillation [49–51], density gradient ultracentrifugation [52] or suspension
precipitation [53], and chromatography – including simple gravity-driven columns [54–56], flash
chromatography [38], MPLC [57–59], HPLC [28], size-exclusion [51], and even gas
chromatography [60].
Among the wider implications of the ubiquitous nature of SDE is the problem of
accurately reporting the enantiomeric purity of chiral compounds isolated from natural sources or
prepared in the laboratory [61–63]. SDE is highly relevant to the field of chirality and
asymmetric synthesis. Understanding SDE is crucial for accurately reporting the stereochemical
outcomes of enantioselective reactions. SDE presents both a challenge and an opportunity in
chemistry, requiring careful consideration and control to avoid errors in experimental results and
interpretation [64–66].
A particularly exciting implication of SDE is related to the origin of prebiotic homochirality.
Among various theories proposed, SDE is the only experimentally proven mechanism for the
formation and maintenance of enantiomerically pure or highly enriched samples [67–69].
SDE and enantiomer purifications. In essence, the SDE phenomenon is the
spontaneous separation of the excess enantiomer from the racemic portion. Therefore,
enantiomer purification is an innate property and the way of SDE manifestation. Thus, the
primary question is how to amplify this spontaneous, innate enantiomer purification to a practical
application level. Research conducted on numerous chiral compounds has identified certain
37https://ucj.org.ua
Alicja Wzorek, Karel D. Klika, Jianlin Han, Alexander E. Sorochinsky, Taizo Ono, Vadim A. Soloshonok UCJ № 3 / Vol. 91
tical levels. As SDE can be used as a method
to obtain enantiopure samples from scalemic
mixtures, it can lead to the development of un-
conventional and superior methods for enan
tiopurification. Particularly exciting results
were reported for the SDE-driven enantiomer
purification via sublimation [71–75] and achi-
ral column chromatography. Figure 2 and Ta-
ble 1 present several examples of various types
of chiral organic compounds.
Table 1. Examples of SDE-driven enantiomer purifications via achiral chromatography.
Entry Cmpd. Starting
ee [%]
Type of
chromato
graphy
Eluent
First
fraction
[%]
Last
fraction
[%]
Δee Yields
[%]
1 1 75.0 (S) flash
c-Hex–benzene–
di-tert-butyl
ether (1:1:0.1)
28.0 >99 63.3 44.0
2 2 78.9 (S) gravity c-Hex/MTBE
(1:2) >99 56.6 43.3 24.0
3 2 71.0 (S) MPLC n-Hex–EtOAc
(1:1) >99 28 71 66.0
4 3 64.9 (R) gravity c-hex/MTBE
(1:2) >99 33.2 66.7 21.7
5 4 72.6 (S) gravity c-hex/MTBE
(1:2) 80.3 79.9 12.6 ‒
6 4 69.0 (S) MPLC n-Hex–EtOAc
(2:1) >99 52.0 47 40.0
7 5 64.2 (P) gravity CH2CL2 >99 44.6 55.3 0.7
8 5 65.8 (P) MPLC n-Hex–EtOAc >99 35.4 63.6 53.6
9 6 34.6 (R) gravity n-Hex–EtOAc
(5:1) 8.1 >99 91.8 4.3
10 7 34.6 (R) gravity c-Hex/EtOAc
(1:5) >99 13.0 86 0.5
11 8 81.4 (S) flash n-Hex–EtOAc 93.5 62.3 31.2 ‒
12 9 72.4 (S) gravity n-Hex–EtOAc
(1:13) 97.0 47.4 49.6 ‒
13 10 82 (M) gravity n-Hex–EtOAc
(3:1) 69 89 20 ‒
38 ISSN 2708-129X. Укр. хім. журн., 2025
ENANTIOMER PURIFICATION THROUGH ACHIRAL CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED
AND SELF-DISPROPORTIONATION OF ENANTIOMERS.ORGANIC CHEMISTRY
Fig. 2. Examples of compounds exhibiting a high magnitude of self-disproportionation of enantiomers
(SDE) under achiral chromatography conditions.
structural classes and functional groups, known as SE-phoric groups [21, 70], that allow for high
magnitudes of SDE, reaching practical levels. As SDE can be used as a method to obtain
enantiopure samples from scalemic mixtures, it can lead to the development of unconventional
and superior methods for enantiopurification. Particularly exciting results were reported for the
SDE-driven enantiomer purification via sublimation [71–75] and achiral column
chromatography. Figure 2 and Table 1 present several examples of various types of chiral organic
compounds.
F3C
OH
NH2 N
MeCH3
O
H
N
O
Me
CO2Et
H Bn
N
O
Me
CO2Et
H
N
N
Me
O Br
Me n-Pentyl
S
O
N
F3C
O
NO2O2N
H
CO2Et
HN
MeO2C
Et
O
N
H
NH
P
O
OEt
OEt
F F
O
Me
S S
SS
OH HO
1 2 3 4
5 6
7 8
9 10
Fig. 2. Examples of compounds exhibiting a high magnitude of self-disproportionation of enantiomers
(SDE) under achiral chromatography conditions.
Table 1. Examples of SDE-driven enantiomer purifications via achiral chromatography.
Entry Cmpd. Starting
ee [%]
Type of
chromatography Eluent First
fraction
Last
fraction Δee
Yields
[%]
Examples 1–10 (Fig.1) were selected to
showcase the structural variety of chiral com-
pounds demonstrating significant SDE magni-
tudes, leading to laboratory-scale enantiomer
purifications. These examples include unpro-
tected amino alcohol 1 [76], amide-protec
ted amine 2 [55, 77, 78], α-amino acid 4 [79],
β-amino acids 3 [54, 57, 80] and 6 [37], phos-
phorus analog of β-amino acid 9 [81], unpro-
tected α-amino ester 8 [82], sulfoxide 7 [39],
compound with axial chirality 5 [83], and heli-
cine 10 [27].
For each compound (1–10), Table 1 pro-
vides data on initial enantiomeric purity, type
of achiral chromatography, eluent, enantio-
meric excess in the first and last fractions, the
difference in enantiomeric excess (Δee), and
the yields of isolated enantiomerically pure
compounds. These data overwhelmingly high-
light the prowess of SDE via achiral chroma-
tography as a general approach for the enantio
purification of scalemic organic compounds.
However, practical application has been se-
verely hindered by difficulties in scaling up
from gram to a practically useful level of 100 g
or more. This is why the breakthrough repor
ted by Dorota Antos’ group [19] represents a
critically needed advancement in this field.
Simulated moving bed chromatography.
Simulated Moving Bed (SMB) chromatography
is an advanced technique used to separate and
purify different components from a mixture
[84-87]. Unlike traditional batch chromatogra-
phy, which processes samples in fixed amounts,
SMB operates continuously, making it more
efficient and cost-effective for large-scale sep-
arations. SMB chromatography consists of se
veral interconnected columns filled with a sta-
39https://ucj.org.ua
Alicja Wzorek, Karel D. Klika, Jianlin Han, Alexander E. Sorochinsky, Taizo Ono, Vadim A. Soloshonok UCJ № 3 / Vol. 91
tionary phase that interacts uniquely with each
component of the mixture. A liquid containing
the mixture flows through the system, and the
continuous alternation of input and output po-
sitions facilitates the separation process, rep-
licating the effect of a moving solid phase. The
number of columns typically used can vary de-
pending on the specific application and scale of
the process. Generally, 8, 12, or 16 columns are
commonly employed. Simplified version of the
SMB system is illustrated in Fig. 2.
Fig. 2. Schematic of SMB units separating a bi-
nary mixture.
SMB consists of several connected columns
filled with a stationary material that inte
racts differently with each component of the
mixture. A liquid carrying the mixture flows
through the system, and due to the constant
switching of input and output positions, the
separation process mimics the effect of a mo
ving solid phase [88–90].
SMB is widely used in industries like phar-
maceuticals, food processing, and petrochem-
icals [91-95]. It offers several benefits such as
higher efficiency, better purity, and cost-effec-
tiveness. SMB is widely used in pharmaceutical
industry for large-scale isolation/purification
of drug components, especially enantiomers
in chiral drugs. In food industry for refining
sugars, amino acids, and other food additives.
More generally, in chemical industry for sepa
ration of petrochemical products and bio-
based chemicals. Overall, while SMB chroma-
tography may seem complex, it is essentially a
smart way of continuously filtering out desired
compounds from mixtures. By improving ef-
ficiency and reducing waste, it plays a crucial
role in modern industry and scientific research.
Case of methyl p-tolyl sulfoxide. The study
under discussion [19] focused on developing
an SDE-driven Achiral Simulated Moving Bed
(SDE-ACh-SMB) process for the separation of
enantiomers of (S)-MTSO (Scheme 1).
in enantiomeric excess (Δee), and the yields of isolated enantiomerically pure compounds. These
data overwhelmingly highlight the prowess of SDE via achiral chromatography as a general
approach for the enantiopurification of scalemic organic compounds. However, practical
application has been severely hindered by difficulties in scaling up from gram to a practically
useful level of 100 g or more. This is why the breakthrough reported by Dorota Antos' group [19]
represents a critically needed advancement in this field.
Simulated moving bed chromatography. Simulated Moving Bed (SMB)
chromatography is an advanced technique used to separate and purify different components from
a mixture [84-87]. Unlike traditional batch chromatography, which processes samples in fixed
amounts, SMB operates continuously, making it more efficient and cost-effective for large-scale
separations. SMB chromatography consists of several interconnected columns filled with a
stationary phase that interacts uniquely with each component of the mixture. A liquid containing
the mixture flows through the system, and the continuous alternation of input and output
positions facilitates the separation process, replicating the effect of a moving solid phase. The
number of columns typically used can vary depending on the specific application and scale of the
process. Generally, 8, 12, or 16 columns are commonly employed. Simplified version of the
SMB system is illustrated in Fig. 2.
Column switching
Eluent
Feed
Fig. 2. Schematic of SMB units separating a binary mixture.
Scheme 1. SDE-driven enantiopurification of scalemic S-MTSO.
SMB consists of several connected columns filled with a stationary material that interacts
differently with each component of the mixture. A liquid carrying the mixture flows through the
system, and due to the constant switching of input and output positions, the separation process
mimics the effect of a moving solid phase [88–90].
SMB is widely used in industries like pharmaceuticals, food processing, and
petrochemicals [91-95]. It offers several benefits such as higher efficiency, better purity, and
cost-effectiveness. SMB is widely used in pharmaceutical industry for large-scale
isolation/purification of drug components, especially enantiomers in chiral drugs. In food
industry for refining sugars, amino acids, and other food additives. More generally, in chemical
industry for separation of petrochemical products and bio-based chemicals. Overall, while SMB
chromatography may seem complex, it is essentially a smart way of continuously filtering out
desired compounds from mixtures. By improving efficiency and reducing waste, it plays a
crucial role in modern industry and scientific research.
Case of methyl p-tolyl sulfoxide. The study under discussion [19] focused on
developing an SDE-driven Achiral Simulated Moving Bed (SDE-ACh-SMB) process for the
separation of enantiomers of (S)-MTSO (Scheme 1).
S
O
(R)-1
S
O
(R)-1
S
O
(S)-1
S
O
(R)-1
Scalemic mixture of MTSO
S
O
S
O
(S/R)-2
Racemic dimer;
Higher retention time
S
O
(R)-1
S
O
(R)-1
+ +
Pure enationers;
Lower retention times
Scheme 1. SDE-driven enantiopurification of scalemic S-MTSO.
Due to identical Henry constants for enantiomers in an achiral environment, conventional
design methods like triangle theory were inapplicable [96–98]. Instead, the approach involved
three steps, including batch-column separation for model calibration, model-aided selection of
operational variables, and experimental adjustment.
Elution experiments helped determine key parameters such as total column porosity (εt),
apparent dispersion coefficient (Da), and isotherm coefficients (qm, KI, KII). The porosity (εt)
averaged 0.70 with minimal deviations between columns. The number of theoretical plates (N ≈
1000) was used to calculate Da, and the isotherm coefficients were estimated using peak fitting
techniques. These parameters ensured accurate predictions of migration velocities for the
enantiomers' fronts during the separation process.
40 ISSN 2708-129X. Укр. хім. журн., 2025
ENANTIOMER PURIFICATION THROUGH ACHIRAL CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED
AND SELF-DISPROPORTIONATION OF ENANTIOMERS.ORGANIC CHEMISTRY
Due to identical Henry constants for enan
tiomers in an achiral environment, conven-
tional design methods like triangle theory were
inapplicable [96–98]. Instead, the approach
involved three steps, including batch-column
separation for model calibration, model-aided
selection of operational variables, and experi-
mental adjustment.
Elution experiments helped determine key
parameters such as total column porosity (εt),
apparent dispersion coefficient (Da), and iso-
therm coefficients (qm, KI, KII). The porosi-
ty (εt) averaged 0.70 with minimal deviations
between columns. The number of theoretical
plates (N ≈ 1000) was used to calculate Da,
and the isotherm coefficients were estimated
using peak fitting techniques. These parame-
ters ensured accurate predictions of migration
velocities for the enantiomers’ fronts during
the separation process.
Initial experiments in batch columns
demonstrated the SDE phenomenon, allowing
the formation of homochiral and heterochiral
associates with different retention properties.
Optimal conditions for batchwise achiral
separation were determined, providing a base-
line for further SMB experiments.
A series of SMB runs were conducted with
varying zone flowrates, switching times, and
feed conditions. The initial scouting run failed
due to incorrect predictions of enantiomer
migration velocities.
Subsequent runs adjusted flowrates and
switching times, achieving high-purity sepa-
ration of S-MTSO enantiomer with improved
productivity and yield. Specifically, run 3
reached approximately 100% purity with a
productivity of 28 grams of (S)-MTSO per liter
of column volume per day.
Variations in feed concentration and enan-
tiomeric excess were investigated. Higher ee
improved product purity and productivity by
enhancing the migration velocity difference
between enantiomers. Increased feed concent
ration intensified the SDE effect, beneficial for
separation performance, but also made main-
taining product purity more challenging due
to the sharper concentration fronts of enan
tiomers.
The dynamic model was verified against
experimental data, confirming its accuracy
and reliability in predicting SMB separation
performance. The model parameters were ad-
justed based on experimental results to ensure
precise predictions.
The ACh-SMB system used for the enantio
purification was equipped with four Smartline
Pumps (model 100 V.5010), a pair of UV de-
tectors (K-2501), an SMB-Control unit, and a
multifunctional valve (CSEP C9 Series Simu-
lated Moving Bed and Chromatography Sys-
tems V0499, 12/2000). All components were
sourced from Knauer.
In showcase experiments the enantiomeric
excess (ee) of the enantioenriched MTSO stream
was maintained at 50%. The yield of the target
enantiomer (S-MTSO) was approximately 26%.
The productivity was 28 grams of S-MTSO per
liter of total column volume per day. These ex-
periments clearly highlighted the key benefits
and effectiveness of the method, providing clear
and compelling evidence of its capabilities. The
reproducibility of the ACh-SMB process was
confirmed through repeated runs, yielding con-
sistent performance indicators.
The developed ACh-SMB process offers a
cost-effective alternative for separating non-
racemic mixtures with high ee, common in
asymmetric synthesis. This method can reduce
reliance on expensive chiral chromatography.
For mixtures with low ee, a tandem configura-
tion with chiral chromatography can improve
41https://ucj.org.ua
Alicja Wzorek, Karel D. Klika, Jianlin Han, Alexander E. Sorochinsky, Taizo Ono, Vadim A. Soloshonok UCJ № 3 / Vol. 91
process economy by recycling the waste frac-
tion.
CONCLUSIONS. A novel SDE-ACh-SMB
process was developed and verified for the
continuous separation of enantiomers from
nonracemic mixtures [19]. The process is fea-
sible, reproducible, and predictable, demon-
strating high potential for industrial applica-
tions. Optimal conditions achieved product
purity of 96–100% and productivity up to
99 grams per liter of column volume per day.
The only drawback of this method is the re-
maining racemic compound, which must be
discarded or resolved using an external chiral
selector. In this regard, one can envision an ad-
vanced methodology presented in Fig. 3. The
process starts with a racemic compound. Using
low-cost chiral chromatography, the racemate
is transformed into two fractions of scalemic
compounds, enantiomerically enriched in
(R)- and (S)-enantiomers, respectively. Next,
the SDE-SMB approach is used to separate the
target enantiomers, and the remaining portion
is fed back to the racemate injector port. Pro
perly designed and working continuously, such
a process will revolutionize the separation of
enantiomers.
Fig. 3. Proposed advanced process for resolu-
tion of racemates using low-cost chiral chromatog-
raphy and the SDE-SMBCh.
Since SDE is an inherent property of all chi-
ral compounds, the SDE-ACh-SMB process is
expected to have the broadest possible applica-
bility in the field of enantiomer purifications.
ОЧИЩЕННЯ ЕНАНТІОМЕРІВ ЗА ДОПОМОГОЮ
АХІРАЛЬНОЇ ХРОМАТОГРАФІЇ: ІНТЕГРАЦІЯ
СИМУЛЬОВАНОГО РУХОМОГО ШАРУ
ТА САМОДИСПРОПОРЦІОНУВАННЯ
ЕНАНТІОМЕРІВ
Аліція Взорек,1 Карел Д. Кліка,2
Джіанлін Хань,3
Олександр Е. Сорочинський,4
Тайзо Оно,5 Вадим А. Солошонок6,7*
1 Інститут хімії, Університет Яна Коханов-
ського в Кельцях, вул. Університетська 7, 25–
406 Кельце, Польща;
2 Центр досліджень і розроблень, Archer Daniels
Midland, 1001 N Brush College Rd., Декейтер, Іл-
лінойс 62521, США;
3 Цзянсу Співдружній центр ефективного оброб
лення і використання лісових ресурсів, Коледж
хімічного машинобудування, Нанкінський лісо-
вий університет, Нанкін 210037, Китай;
4 Інститут біоорганічної хімії та нафтохімії
ім. В. П. Кухаря, Національна академія наук
України, вул. Академіка Кухаря, 1, Київ 02094,
Україна;
5 Національний інститут передових промисло-
вих наук і технологій (AIST), 2266–98, Анагаго-
ра, Шимошидамі, Моріяма-ку, Нагоя, 463–8560,
Японія;
6 Кафедра органічної хімії I, Факультет хімії,
Університет Країни Басків UPV/EHU, Пасаео
Мануель Лардісабаль 3, 20018 Сан Себастьян,
Іспанія;
7 IKERBASQUE, Баскський фонд науки, вул. Ма-
рія Діас де Харо 3, площа Бізкая, 48013 Більбао,
Іспанія
low cost
chiral SMB
racemate
(S)-scalemate
(R)-scalemate
SDE-SMB
pure (S)
enantiomer
pure (R)
enantiomer
SDE-SMB
Fig. 3. Proposed advanced process for resolution of racemates using low-cost chiral chromatography and
the SDE-SMBCh.
Since SDE is an inherent property of all chiral compounds, the SDE-ACh-SMB process is
expected to have the broadest possible applicability in the field of enantiomer purifications.
ОЧИЩЕННЯ ЕНАНТІОМЕРІВ ЗА ДОПОМОГОЮ АХІРАЛЬНОЇ ХРОМАТОГРАФІЇ:
ІНТЕГРАЦІЯ СИМУЛЬОВАНОГО РУХОМОГО ШАРУ ТА САМОДИСПРОПОРЦІОНУВАННЯ
ЕНАНТІОМЕРІВ.
Аліція Взорек,1 Карел Д. Кліка,2 Джіанлін Хань,3 Олександр Е. Сорочинський,4 Тайзо
Оно,5 Вадим А. Солошонок,6,7*
1 Інститут хімії, Університет Яна Кохановського в Кельцях, вул. Університетська 7, 25–406
Кельце, Польща;
2 Центр досліджень і розроблень, Archer Daniels Midland, 1001 N Brush College Rd., Декейтер,
Іллінойс 62521, США;
3 Цзянсу Співдружній центр ефективного оброблення і використання лісових ресурсів, Коледж
хімічного машинобудування, Нанкінський лісовий університет, Нанкін 210037, Китай;
4 Інститут біоорганічної хімії та нафтохімії ім. В. П. Кухаря, Національна академія наук України,
вул. Академіка Кухаря, 1, Київ 02094, Україна;
5 Національний інститут передових промислових наук і технологій (AIST), 2266–98, Анагагора,
Шимошидамі, Моріяма-ку, Нагоя, 463–8560, Японія;
6 Кафедра органічної хімії I, Факультет хімії, Університет Країни Басків UPV/EHU, Пасаео
Мануель Лардісабаль 3, 20018 Сан Себастьян, Іспанія;
7 IKERBASQUE, Баскський фонд науки, вул. Марія Діас де Харо 3, площа Бізкая, 48013 Більбао,
Іспанія
Очищення енантіомерів є важливим процесом у фармацевтичній, агрохімічній та харчовій
промисловості, де хіральні сполуки часто виявляють різну біологічну активність. Традиційна
хіральна хроматографія є ефективною, але дорогою через використання дорогих хіральних
стаціонарних фаз. Ця оглядова стаття висвітлює останній прорив у очищенні енантіомерів в
умовах повністю ахіральних умов. Зокрема, акцент зроблено на поєднанні ахіральної симульованої
42 ISSN 2708-129X. Укр. хім. журн., 2025
ENANTIOMER PURIFICATION THROUGH ACHIRAL CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED
AND SELF-DISPROPORTIONATION OF ENANTIOMERS.ORGANIC CHEMISTRY
Очищення енантіомерів є важливим
процесом у фармацевтичній, агрохіміч-
ній та харчовій промисловості, де хіральні
сполуки часто виявляють різну біологічну
активність. Традиційна хіральна хромато-
графія є ефективною, але дорогою через
використання дорогих хіральних стаціо-
нарних фаз. Ця оглядова стаття висвітлює
останній прорив у очищенні енантіомерів в
умовах повністю ахіральних умов. Зокрема,
акцент зроблено на поєднанні ахіральної
симульованої рухомої шарової хроматогра-
фії та феномена самодиспропорціонування
енантіомерів (SDE). Експериментальна пе-
ревірка з використанням скалемічного ме-
тил-р-толуїлсульфоксиду як модельної спо-
луки дозволила ізолювати надлишковий
енантіомер із високою чистотою (~99% ee)
та поважним виходом (~50%). Цей іннова-
ційний процес характеризується винятко-
вою продуктивністю (до 99 грамів на літр
об’єму колони на день), відтворюваністю та
надійністю. Цей прорив являє собою пер-
ший практичний приклад очищення енан-
тіомерів на основі SDE, пропонуючи масш-
табовану та економічно доцільну альтерна-
тиву традиційним хіральним розділенням.
Враховуючи, що SDE є властивістю всіх
хіральних сполук, цей інноваційний підхід
очікувано має стати пріоритетним методом
для практичного очищення енантіомерів
як у дослідженнях, так і в промисловому
виробництві.
Ключові слова: хіральність, енантіоме-
ри, очищення, самодиспропорціонування
енантіомерів (SDE), ахіральна хроматогра-
фія, симульована рухома шарова хромато-
графія.
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Стаття надійшла 04.02.2025.
|
| id | oai:ojs2.1444248.nisspano.web.hosting-test.net:article-714 |
| institution | Ukrainian Chemistry Journal |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-23T01:12:49Z |
| publishDate | 2025 |
| publisher | V.I.Vernadsky Institute of General and Inorganic Chemistry |
| record_format | ojs |
| resource_txt_mv | ucjorgua/6d/755810d9fe461359e94f90126be7b46d.pdf |
| spelling | oai:ojs2.1444248.nisspano.web.hosting-test.net:article-7142026-07-22T08:23:55Z ENANTIOMER PURIFICATION THROUGH ACHIRAL CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED AND SELF-DISPROPORTIONATION OF ENANTIOMERS Wzorek, Alicja Klika, Karel Han, Jianlin Sorochinsky, Alexander Ono, Taizo Soloshonok, Vadim Chirality, Enantiomers, Purification, Self-Disproportionation of Enantiomers (SDE), Achiral Chromatography, Simulated Moving Bed Chromatography. Enantiomer purification is a critical process in the pharmaceutical, agrochemical, and food industries, where chiral compounds often exhibit distinct biological activities. Traditional chiral chromatography is effective but costly due to the use of expensive chiral stationary phases. This review article highlights a recent breakthrough in enantiomer purification under entirely achiral conditions. Specifically, it focuses on the convergence of achiral simulated moving bed chromatography and the phenomenon of self-disproportionation of enantiomers (SDE). Experimental validation using scalemic methyl p-tolyl sulfoxide as a model compound enabled the isolation of the excess enantiomer with high purity (99% ee) and a respectable yield (~50%). This innovative process features exceptional productivity (up to 99 grams per liter of column volume per day), reproducibility, and reliability. This breakthrough presents the first practical example of enantiomer purification based on SDE, offering a scalable and economically viable alternative to conventional chiral separations. Given that SDE is an inherent property of all chiral compounds, this innovative approach is anticipated to become the method of choice for practical enantiomer purification in both research and industrial production. V.I.Vernadsky Institute of General and Inorganic Chemistry 2025-04-25 Article Article Organic chemistry Органическая xимия Органічна xімія application/pdf https://ucj.org.ua/index.php/journal/article/view/714 10.33609/2708-129X.91.3.2025.34-48 Ukrainian Chemistry Journal; Vol. 91 No. 3 (2025): Ukrainian Chemistry Journal; 34-48 Украинский химический журнал; ##issue.vol## 91 ##issue.no## 3 (2025): Ukrainian Chemistry Journal; 34-48 Український хімічний журнал; Том 91 № 3 (2025): Ukrainian Chemistry Journal; 34-48 2708-129X 2708-1281 en https://ucj.org.ua/index.php/journal/article/view/714/362 Copyright (c) 2025 Alicja Wzorek, Karel Klika, Jianlin Han, Alexander Sorochinsky, Taizo Ono, Vadim Soloshonok https://creativecommons.org/licenses/by-nc/4.0 |
| spellingShingle | Wzorek, Alicja Klika, Karel Han, Jianlin Sorochinsky, Alexander Ono, Taizo Soloshonok, Vadim ENANTIOMER PURIFICATION THROUGH ACHIRAL CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED AND SELF-DISPROPORTIONATION OF ENANTIOMERS |
| title | ENANTIOMER PURIFICATION THROUGH ACHIRAL CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED AND SELF-DISPROPORTIONATION OF ENANTIOMERS |
| title_full | ENANTIOMER PURIFICATION THROUGH ACHIRAL CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED AND SELF-DISPROPORTIONATION OF ENANTIOMERS |
| title_fullStr | ENANTIOMER PURIFICATION THROUGH ACHIRAL CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED AND SELF-DISPROPORTIONATION OF ENANTIOMERS |
| title_full_unstemmed | ENANTIOMER PURIFICATION THROUGH ACHIRAL CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED AND SELF-DISPROPORTIONATION OF ENANTIOMERS |
| title_short | ENANTIOMER PURIFICATION THROUGH ACHIRAL CHROMATOGRAPHY: INTEGRATING SIMULATED MOVING BED AND SELF-DISPROPORTIONATION OF ENANTIOMERS |
| title_sort | enantiomer purification through achiral chromatography: integrating simulated moving bed and self-disproportionation of enantiomers |
| topic_facet | Chirality Enantiomers Purification Self-Disproportionation of Enantiomers (SDE) Achiral Chromatography Simulated Moving Bed Chromatography. |
| url | https://ucj.org.ua/index.php/journal/article/view/714 |
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