Ферментативні підходи до отримання α-амінофосфонових кислот та фторвмісних β-амінокислот
In this perspective review article, we discuss application of penicillin acylase for biocatalytic resolution of tailor-made amino acids, in particular α-aminophosphonic acids and fluorine-containing β-amino acids. The method includes preparation of the corresponding N-phenylacetyl derivatives follow...
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V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine
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| author | Wzorek, Alicja Han, Jianlin Lyutenko, Nataliya V. Koley, Manankar Sorochinsky, Alexander E. Ono, Taizo Soloshonok, Vadim A. |
| author_facet | Wzorek, Alicja Han, Jianlin Lyutenko, Nataliya V. Koley, Manankar Sorochinsky, Alexander E. Ono, Taizo Soloshonok, Vadim A. |
| author_institution_txt_mv | [
{
"author": "Alicja Wzorek",
"institution": "Institute of Chemistry, Jan Kochanowski University in Kielce, Kielce, Poland "
},
{
"author": "Jianlin Han",
"institution": "College of Chemical Engineering, Nanjing Forestry University, Nanjing, China"
},
{
"author": "Nataliya V. Lyutenko",
"institution": "V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry, The National Academy of Sciences of Ukraine, 1 Murmanska str., Kyiv 02094, Ukraine"
},
{
"author": "Manankar Koley",
"institution": "CSIR-Central Glass & Ceramic Research Institute, Kolkata, India"
},
{
"author": "Alexander E. Sorochinsky",
"institution": "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 (AIST), Anagahora, Shimoshidami, Moriyama-ku, Nagoya, Japan"
},
{
"author": "Vadim A. Soloshonok",
"institution": "Department of Organic Chemistry I, University of the Basque Country, San Sebastián, Spain; IKERBASQUE, Basque Foundation for Science, Bilbao, Spain"
}
] |
| author_sort | Wzorek, Alicja |
| baseUrl_str | https://bioorganica.com.ua/index.php/journal/oai |
| collection | OJS |
| datestamp_date | 2026-07-19T14:56:55Z |
| description | In this perspective review article, we discuss application of penicillin acylase for biocatalytic resolution of tailor-made amino acids, in particular α-aminophosphonic acids and fluorine-containing β-amino acids. The method includes preparation of the corresponding N-phenylacetyl derivatives followed by the enzyme-catalyzed hydrolysis of one of the enantiomers. The free amino acid and the remaining N-phenylacetyl derivative are separated simply by cation-exchange chromatography or extraction. The final step is a chemical hydrolysis of the enzymatically unreactive N-phenylacetyl derivative. This approach features exceptionally high enantiomeric purity (>99% ee) of the target amino acids, wide structural generality and operational simplicity boding well for large-scale applications of this biocatalytic approach for preparation of highly biologically relevant unnatural, tailor-made amino acids in enantiomerically pure form |
| doi_str_mv | 10.15407/bioorganica2024.01.021 |
| first_indexed | 2025-07-17T12:20:00Z |
| format | Article |
| fulltext |
ISSN 1814-9758. Ukr. Bioorg. Acta, 2024, Vol. 19, N 1
UDC 547.484.2
DOI: https://doi.org/10.15407/bioorganica2024.01.021
21
REVIEW
Enzymatic approaches for preparation of α-aminophosphonic acids and
fluorine-containing β-amino acids
Alicja Wzorek1, Jianlin Han2, Nataliya V. Lyutenko3, Manankar Koley4, Alexander E. Sorochinsky3,
Taizo Ono5, Vadim A. Soloshonok6,7*
1 Institute of Chemistry, Jan Kochanowski University in Kielce, Kielce, Poland
2 College of Chemical Engineering, Nanjing Forestry University, Nanjing, China
3 V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Kyiv, Ukraine
4 CSIR-Central Glass & Ceramic Research Institute, Kolkata, India
5 National Institute of Advanced Industrial Science and Technology (AIST), Anagahora, Shimoshidami, Moriyama-ku, Nagoya, Japan
6 University of the Basque Country, San Sebastián, Spain
7 IKERBASQUE, Basque Foundation for Science, Bilbao, Spain
Abstract: In this perspective review article, we discuss application of penicillin acylase for biocatalytic resolution of tailor-made amino
acids, in particular α-aminophosphonic acids and fluorine-containing β-amino acids. The method includes preparation of the corresponding
N-phenylacetyl derivatives followed by the enzyme-catalyzed hydrolysis of one of the enantiomers. The free amino acid and the remaining
N-phenylacetyl derivative are separated simply by cation-exchange chromatography or extraction. The final step is a chemical hydrolysis
of the enzymatically unreactive N-phenylacetyl derivative. This approach features exceptionally high enantiomeric purity (>99% ee) of the
target amino acids, wide structural generality and operational simplicity boding well for large-scale applications of this biocatalytic
approach for preparation of highly biologically relevant unnatural, tailor-made amino acids in enantiomerically pure form.
Keywords: penicillin acylase; enantioselective kinetic resolution; hydrolytic diacylation; 1-aminoalkylphosphonic acids; 1-aminoalkyl-
phosphinic acids; β-fluoroalkyl-β-amino acids; α-alkyl-β-fluoroalkyl-β-amino acids.
Introduction
Tailor-made amino acids (AAs) [1] are indispensable
molecular units of modern medicinal chemistry and are
becoming increasingly prominent in new marketed drugs
[2]. In fact, about 35% of small-molecule pharmaceuticals
contain residues of tailor-made AAs, including structurally
AA-derived diamines and amino-alcohols [3]. Furthermore,
the growing number of peptide and peptidomimetic-based
medicines underscores the privileged place of AAs in
modern health industry [4]. The unique role of AAs in the
Received:
Revised:
Accepted:
Published online:
10.04.2024
13.05.2024
20.05.2024
30.06.2024
Corresponding author. Tel.: +34-94-301-5177;
e-mail: vadym.solosholok@ehu.es (V.A. Soloshonok)
ORCID: 0000-0003-0681-4526
drug design can be rationalized considering their synthetic
availability [5] and practically unlimited structural diversity
offered by two orthogonal functional groups, side-chains
and one or more stereogenic centers. Phosphorus analogs of
AAs as structural analogues and mimetics of α-amino acids
represent an important class of tailor-made AAs which are
of great interest for pharmaceutical and agrochemical
research for many years in their own right [6] or as a part of
structurally more complex molecules [7]. However, the
medicinal potential of phosphorus analogs of AAs is not
fully explored yet. In particular, incorporation of
phosphorus analogs of AAs into peptides and
peptidomimetics [8] may unlock exciting modes of
peptides’ 3D-structure and bioactivity. On the other hand,
fluorine-containing tailor-made AAs have been in focus of
medicinal chemistry for quite some time now and numerous
drugs featuring their residues are currently on the
pharmaceutical market [9]. Both types of these tailor-made
AAs have been actively studied by the group of
Academician V.P. Kukhar [10] as a part of a more general
© Wzorek A. et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original author and source are credited.
Ukrainica Bioorganica Acta
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ISSN 1814-9758. Ukr. Bioorg. Acta, 2024, Vol. 19, N 1
22
Scheme 1. Synthesis of racemic N-phenylacetylated 1-aminoalkylphosphonic acids 2.
scientific exploration of biologically active compounds
containing phosphorus or fluorine atoms [11]. In this
regard, preparation of the target compounds in
enantiomerically pure form was an essential step in accurate
assessment of their potential medicinal applications [12]. In
this review article, we discuss an important discovery made
by Kukhar's group with innovative application of penicillin
acylase for biocatalytic resolution of tailor-made amino
acids, in particular α-aminophosphonic acids and fluorine-
containing β-amino acids.
Preparation of enantiomerically pure α-amino-
phosphonic acids
Among the many asymmetric synthetic methods for the
preparation of α-aminophosphonic acid derivatives [13],
enzymatic resolution of racemic mixtures of these
compounds has become a simple and economical
alternative to chemical procedures [14]. Kuchar's group
performed an extensive study of the penicillin acylase-
mediated kinetic resolution of racemic N-phenylacetylated
Scheme 2. Penicillin acylase-mediated kinetic resolution of racemic N-phenylacetylated 1-aminoalkylphosphonic acids 2.
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A. Wzorek, J. Han, et al.
23
Scheme 3. Penicillin acylase-mediated kinetic resolution of racemic N-phenylacetylated 1-aminoethylphosphinic acid 5.
1-aminoalkylphosphonic acids to elucidate the relation
between substrate structure and reaction conditions with the
stereoselectivity of enzymatic hydrolytic diacylation.
Penicillin acylase is commercially available and stable
enzyme that selectively hydrolyses the derivatives of
phenylacetic acid. The N-phenylacetylated 1-amino-
alkylphosphonic acids 2 were prepared as racemic mixtures
by reaction of 1-aminoalkylphosphonic acids (R/S)-1 with
phenylacetyl chloride according to Schotten-Baumann
procedure using sodium bicarbonate as a base at low
temperature in water-acetone solution (method A), or with
N-hydroxysuccinimide ester of phenylacetic acid in aqueous
DMF in the presence of a tertiary amine (method B)
(Scheme 1) [15]. The N-phenylacetylated 1-aminoalkyl-
phosphonic acids (R/S)-2 were also formed by acylation of
l-aminoalkylphosphonic acid diisopropyl esters (R/S)-3 with
phenylacetyl chloride followed by P-deprotection of
corresponding diisopropyl esters (R/S)-4 with trimethylsilyl
bromide (method C). The resulting N-phenylacetylated
acids (R/S)-2 were easily purified by cation-exchange
chromatography or recrystallization for biocatalytic
resolution. The enzymatic hydrolysis of racemic 1-(N-phe-
nylacetylamino)alkylphosphonic acids 2 in the presence of
penicillin acylase was performed in phosphate buffer
(pH 6.8-7.0) at the substrate/enzyme molar ratio 6.7.105 to
give both the corresponding 1-aminoalkylphosphonic acids
(R)-1 in high yields and excellent optical purity and the
unreacted substrates (S)-2, which were then separated
by cation-exchange chromatography (Scheme 2) [15].
1-Aminoalkylphosphonic acids (S)-1 were isolated after
subsequent hydrolysis of unreacted substrates (S)-2 with
concentrated HCl and crystallization. It should be noted that
changing the time of enzymatic reaction from 2 to 24 hours
did not affect the yield and optical purity of 1-amino-
alkylphosphonic acids (R)-1. Thus, enzyme preferentially
converted the (R)-form of the substrates and, for example,
the ratio of the bimolecular rate constants of penicillin
acylase-catalysed hydrolysis of (R) and (S)-forms of 1-N-
phenylacetaminolethylphosphonic acid 2 achieved a value
of 58000. At the same time, increase of enzyme
concentration in 50-100 times as compared to that used for
preparation of 1-aminoalkylphosphonic acids (R)-1 allowed
hydrolysis of the (S) enantiomers of the substrate within
3-4 days affording 1-aminoalkylphosphonic acids (S)-1 in
good yield and excellent optical purity [16].
1-Aminophosphinic acids are also considered as
analogues of α-amino acids with synthetic and
pharmacological interest [17]. Unfortunately, the hydrolysis
of N-phenylacetylated 1-aminoethylphosphinic acid (R/S)-5
by penicillin acylase, contrary to 1-N-phenylacetyl-
aminoalkylphosphonic acids (R/S)-2, proceeds with
moderate enantioselectivity due to the relatively high rate of
(S)-substrate hydrolysis in this enzymatic process [18].
Nevertheless, after optimization of reaction conditions,
enzymatic hydrolysis of racemic 1-N-phenylacetylamino-
ethylphosphinic acids 5 proceeded efficiently at low
enzyme concentration in water (pH 7.95) for 1.5 h affording
after isolation by cation-exchange chromatography 1-ami-
noethylphosphinic acid (R)-6 in 80% yield with 94% ee
(Scheme 3). The unreacted substrates (S)-5 was then
subjected to additional enzymatic hydrolysis also at low
enzyme concentration over a period of 36 h at room
temperature. The resulting 1-aminoethylphosphinic acid
(S)-6 was obtained in 83% yield with >99% ee. Thus, due to
moderate enantioselectivity of penicillin acylase hydrolysis
of 1-N-phenylacetylaminoethylphosphinic acid (R/S)-5 the
process should be carefully controlled to achieve high
enantiomerical purity of the target products.
General aspects of synthesis of fluorine-containing
amino acids
AAs are among a handful of principal classes of organic
compounds innately involved in the origin and evolution of
life. Since their structural characterization in the early
1800's [19], AAs continue to play a critical role in the
progress of numerous areas of health sciences and
technology [20]. A great number of AAs have been isolated
from natural sources [21] while thousands of tailor-made
variants have been prepared in research laboratories [22]. In
most of cases, asymmetric synthesis of fluorine-containing
α-AAs can be achieved by using fluorinated reagents in
adaptation of the general methods developed for preparation
of non-fluorinated types of AAs [23]. For example,
Kukhar’s school reported synthesis of numerous fluorine-
ISSN 1814-9758. Ukr. Bioorg. Acta, 2024, Vol. 19, N 1
24
containing tailor-made AAs using transition metal-
catalyzed aldol addition reactions [24], chiral sulfoxide
assisted reactions [25] and dynamic kinetic resolution-
deracemization approach [26]. Of particular synthetic
versatility was found the approach based on homologation
of Ni(II) complexes of chiral Schiff bases (Scheme 4).
Thus, under the conditions of alkylation [27], aldol [28],
Michael [29] or Mannich [30] addition reactions Ni(II)
complex (S)-7 can be readily transformed into the tailor-
made AAs (S)-9 along with recovery and reuse of the
corresponding chiral ligand which can be reassembled back
to the starting Ni(II) complex (S)-7. This approach can be
used for a large-scale preparation of the target AAs [31] as
well as synthesis of cyclic molecules such as, for example,
pyroglutamic acids [32], derivatives of thalidomide [33] and
amino‐2‐vinylcyclopropane‐1‐carboxylic acid [34]. By
contrast, adaptation of the known methods for asymmetric
synthesis of β-AAs for preparation of the fluorinated
analogs [35] turned out to be a challenging task. Thus,
while some successful results were obtained in the
asymmetric synthesis of fluorinated β-AAs using 1,3-proton
shift reaction [36], Ni(II) complex homologation [37] or
other methods [38], these approached could not offer the
sought after general synthetic methodology for preparation
of fluorinated β-AAs in enantiomerically pure form. On the
other hand, the discovered by Kukhar school 1,3-proton
shift reaction [39] provided reliable, simple, and structurally
diverse method for synthesis of racemic fluorinated β-AAs.
Consequently, the research was focused on possibility of an
enzymatic resolution of the corresponding readily available
racemic mixtures.
Scheme 4. Asymmetric synthesis of α-AAs using chiral Ni(II)
complexes.
Biocatalytic resolution of β-substituted-β-amino
acids
Despite the prominent role of biocatalytic resolution in
preparation of enantiomerically pure α-AAs, the use of
enzymes for the resolution of β-AAs is virtually unknown
[40]. Drawing inspiration from the results obtained in
resolution of racemic α-amino phosphonic acids, discussed
in the previous section, application of penicillin acylase for
biocatalytic resolution of fluorinated β-amino acids was
investigated as presented in Scheme 5 [41]. Thus, racemates
10 were first transformed into corresponding N-phenyl-
acetyl derivatives (R/S)-11 using phenylacetyl chloride and
triethylamine in acetone. Next, the enantioselective
hydrolysis of (S) enantiomers of 10 was achieved in the
presence of penicillin acylase at ambient temperature. It
should be noted that enzyme-catalyzed hydrolysis was
exceptionally enantioselective as the optical purity of free
amino acids (S)-10 and unreactive amides (R)-11 was
determined to be >99% ee. The remaining N-phenylacetyl
derivatives (R)-11 were hydrolyzed using regular chemical
acidic conditions to furnish free (R)-configured amino acids
10 [42, 43]. This enzymatic method was shown to be high
structural generality as other types of α- and β-AAs such as
phenylalanine, phenylserine, phenylglycine can be
efficiently resolved under the same conditions [44-46].
Enzymatic resolution of α,β-disubstituted-β-amino
acids
Combination of the biomimetic transamination approach
with the penicillin acylase catalyzed resolution was
successfully realized in a chemo-enzymatic approach for
synthesis of all four possible stereoisomers of sterically
constrained α,-disubstituted--amino acids (Scheme 6)
[47,48]. Commercially available racemic keto ester 12 was
transformed into a mixture of enamine 13, as a major
compound, and ketimine 14, as a minor product.
Biomimetic base-catalyzed 1,3-proton shift transfer
conducted on the mixture 13 and 14 gave rise to
diastereomeric products (2R*,3S*)-15 and (2R*,3R*)-15.
Attempts to control the diastereoselectivity of the
1,3-proton shift transfer revealed an interesting trend. Thus,
application of triethylamine as a base favored the (2R*,3S*)
diastereomer 15 (40% de), while the use of DBU afforded
(2R*,3R*) diastereomer 15 as the major product (39% de).
Most likely, the former reaction occurs under thermo-
dynamic conditions, while the latter reflect the kinetically
controlled stereoselectivity. Schiff bases (2R*,3S*)-15 and
(2R*,3R*)-15 can be separated by routine column
chromatography, thus affording an opportunity to work with
diastereomerically pure compounds. Each diastereomer 15
was transformed to the corresponding N-phenylacetyl
derivatives (2R*,3S*)-16 and (2R*,3R*)-16 and subjected to
the kinetic resolution using penicillin acylase. The enzyme-
catalyzed hydrolysis favored the enantiomers possessing
(3R) stereogenic carbon with the rate of higher than 1 to
1000. Such extraordinary enantioselectivity allowed for a
complete resolution with excellent chemical yields of both
enantiomers. Free amino acids (2S,3R)-17 and (2R,3R)-17
can be conveniently separated from the corresponding
unhydrolyzed enantiomers (2R,3S)-16 and (2S,3S)-16,
which can be hydrolyzed under conventional acidic
conditions to produce the corresponding amino acids.
It should be mentioned that the research on asymmetric
synthesis and enzymatic resolutions of fluorinated β-AAs,
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A. Wzorek, J. Han, et al.
25
R
O
OH
NH2
(R/S)-10
R
O
OH
NH
(R/S)-11
O
Ph
penicillin
acylase
R
O
OH
NH2
(S)-10
+
R
O
OH
NH
(R)-11
O
Ph
R
O
OH
NH2
(R)-10
R = CH3, Ph,CF3, C2F5
C3F7, 2-F-C6H4, 4-F-C6H4
PhCH2C
NEt3, H2O, Me2CO pH 7.5
6 N HCI
O
Cl
Scheme 5. Enzymatic resolution of fluorinated β-amino acids.
1412 13
F3C
O
COOEt
H2N Ph F3C
N O
OEt F3C
N O
OEt
H
Ph Ph
TEA, 75 oC
F3C
N O
OEt
Ph
F3C
N O
OEt
Ph
(2R*,3S*)-15 (2R*,3R*)-15
1. 3N HCl
2. PhCH2COCl
F3C
NH O
OH F3C
NH O
OH
(2R*,3S*)-16 (2R*,3R*)-16
penicillin acylase
O
Ph
O
Ph
F3C
NH O
OH F3C
NH2 O
OH
(2S,3S)-16 (2R,3R)-17
Ph
F3C
NH O
OH F3C
NH2 O
OH
(2R,3S)-16 (2S,3R)-17
O
Ph
DBU rt
O
Scheme 6. Enzymatic resolution of α,β-di-substituted-β-amino acids.
made a significant contribution to the discovery of the
phenomenon of Self-Disproportionation of Enantiomers
(SDE) [49]. Subsequent study by Kukhar group [50] has
showed the SDE is a profoundly ubiquitous being
manifested under routine conditions of achiral
chromatography [51], sublimation [52] and even achiral
gas-chromatography [53]. It is interesting to note that
fluorine-containing compounds in general [54], and β-AAs
in particular [55], usually show very high magnitude of the
SDE allowing to use this phenomenon as
enantiopurification method. General recognition of the SDE
prompted some academic journals to require the SDE-tests
as a part of submitted experimental data [56].
Conclusions
While application of enzymes for resolution of racemic
mixtures is one of the most frequently used approached in
academy and industry, their use for preparation of
enantiomerically pure α-aminophosphonic acids and
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ISSN 1814-9758. Ukr. Bioorg. Acta, 2024, Vol. 19, N 1
26
fluorine-containing β-amino acids is still mostly limited to
the research discussed in this article. As pointed out, quite
innovative application of commercially available penicillin
acylase afforded a reliable, generalized and operationally
convenient approach for preparation of α-aminophosphonic
acids and fluorine-containing β-amino acids in
enantiomerically pure form.
Notes
The authors declare no conflict of interest
Author contributions. The manuscript was written with
contributions of all authors. All authors have given approval
to the final version of the manuscript.
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Ферментативні підходи до отримання α-амінофосфонових кислот та фторoвмісних
β-амінокислот
А. Взорек1, Ц. Хань2, Н.В. Лютенко3*, M. Колей4, О.Є. Сорочинський3, Т. Оно5, В.A. Солошонок6,7
1 Інститут Хімії, Університет імені Яна Кохановського в Кельцях, Кельці, Польща
2 Нанкінський лісотехнічний університет, Нанкін, КНР
3 Інститут біоорганічної хімії та нафтохімії ім. В.П. Кухаря НАН України, Київ, Україна
4 CSIR-Центральний інститут досліджень скла і кераміки, Колката, Індія
5 Національний інститут передових промислових наук і технологій (AIST), Анагахора,Шімосідамі, Моріяма-ку, Нагоя, Японія
6 Університет Країни Басків, Сан-Себастьян, Іспанія
7 ІКЕРБАСК, Баскський фонд науки, Більбао, Іспанія
Резюме: У цій оглядовій статті ми розглядаємо застосування пеніцилінацилази для біокаталітичного розділення різноманітних неприродних
амінокислот, зокрема α-амінофосфонових кислот і фторвмісних β-амінокислот. Спосіб включає одержання відповідних N-фенілацетилпохідних з
подальшим ферментативно-каталізованим гідролізом одного з енантіомерів. Вільну амінокислоту та N-фенілацетилпохідну, що залишилася,
відокремлюють за допомогою катіонообмінної хроматографії або екстракції. Останньою стадією є хімічний гідроліз ферментативно неактивного
N-фенілацетилпохідного амінокислоти. Цей загальний підхід характеризується винятково високою енантіомерною чистотою (>99% її) цільових
амінокислот, та операційною простотою, що забезпечує широкомасштабне застосування цього біокаталітичного підходу для отримання
біологічно значущих неприродних амінокислот в енантіомерно чистій формі.
Ключові слова: пеніцилін ацилаза; енантіоселективне кінетичне розділення; гідролітичне діацилювання; 1 -аміноалкілфосфонові кислоти; 1-
аміноалкілфосфінові кислоти; β-фторалкіл-β-амінокислоти; α-алкіл-β-фторалкіл-β-амінокислоти.
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| id | oai:ojs2.bioorganica.com.ua:article-81 |
| institution | Ukrainica Bioorganica Acta |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-07-20T01:01:24Z |
| publishDate | 2024 |
| publisher | V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine |
| record_format | ojs |
| resource_txt_mv | bioorganicacomua/e5/ee9896209fe48136ff84b367e40319e5.pdf |
| spelling | oai:ojs2.bioorganica.com.ua:article-812026-07-19T14:56:55Z Enzymatic approaches for preparation of α-aminophosphonic acids and fluorine-containing β-amino acids Ферментативні підходи до отримання α-амінофосфонових кислот та фторвмісних β-амінокислот Wzorek, Alicja Han, Jianlin Lyutenko, Nataliya V. Koley, Manankar Sorochinsky, Alexander E. Ono, Taizo Soloshonok, Vadim A. penicillin acylase enantioselective kinetic resolution hydrolytic diacylation 1-aminoalkylphosphonic acids 1-aminoalkyl-phosphinic acids α-alkyl-β-fluoroalkyl-β-amino acids пеніцилін ацилаза енантіоселективне кінетичне розділення гідролітичне діацилювання 1-аміноалкілфосфонові кислоти 1-аміноалкілфосфінові кислоти β-фторалкіл-β-амінокислоти α-алкіл-β-фторалкіл-β-амінокислоти In this perspective review article, we discuss application of penicillin acylase for biocatalytic resolution of tailor-made amino acids, in particular α-aminophosphonic acids and fluorine-containing β-amino acids. The method includes preparation of the corresponding N-phenylacetyl derivatives followed by the enzyme-catalyzed hydrolysis of one of the enantiomers. The free amino acid and the remaining N-phenylacetyl derivative are separated simply by cation-exchange chromatography or extraction. The final step is a chemical hydrolysis of the enzymatically unreactive N-phenylacetyl derivative. This approach features exceptionally high enantiomeric purity (>99% ee) of the target amino acids, wide structural generality and operational simplicity boding well for large-scale applications of this biocatalytic approach for preparation of highly biologically relevant unnatural, tailor-made amino acids in enantiomerically pure form У цій оглядовій статті ми розглядаємо застосування пеніцилінацилази для біокаталітичного розділення різноманітних неприродних амінокислот, зокрема α-амінофосфонових кислот і фторвмісних β-амінокислот. Спосіб включає одержання відповідних N-фенілацетилпохідних з подальшим ферментативно-каталізованим гідролізом одного з енантіомерів. Вільну амінокислоту та N-фенілацетилпохідну, що залишилася, відокремлюють за допомогою катіонообмінної хроматографії або екстракції. Останньою стадією є хімічний гідроліз ферментативно неактивного N-фенілацетилпохідного амінокислоти. Цей загальний підхід характеризується винятково високою енантіомерною чистотою (>99% її) цільових амінокислот, та операційною простотою, що забезпечує широкомасштабне застосування цього біокаталітичного підходу для отримання біологічно значущих неприродних амінокислот в енантіомерно чистій формі V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine 2024-06-30 Article Article application/pdf https://bioorganica.com.ua/index.php/journal/article/view/81 10.15407/bioorganica2024.01.021 Ukrainica Bioorganica Acta; Vol. 19 No. 1 (2024): Ukrainica Bioorganica Acta; 21-29 Ukrainica Bioorganica Acta; Том 19 № 1 (2024): Ukrainica Bioorganica Acta; 21-29 1814-9766 1814-9758 10.15407/bioorganica2024.01 en https://bioorganica.com.ua/index.php/journal/article/view/81/79 Copyright (c) 2024 Alicja Wzorek, Jianlin Han, Nataliya V. Lyutenko, Manankar Koley, Alexander E. Sorochinsky, Taizo Ono, Vadim A. Soloshonok https://creativecommons.org/licenses/by/4.0 |
| spellingShingle | пеніцилін ацилаза енантіоселективне кінетичне розділення гідролітичне діацилювання 1-аміноалкілфосфонові кислоти 1-аміноалкілфосфінові кислоти β-фторалкіл-β-амінокислоти α-алкіл-β-фторалкіл-β-амінокислоти Wzorek, Alicja Han, Jianlin Lyutenko, Nataliya V. Koley, Manankar Sorochinsky, Alexander E. Ono, Taizo Soloshonok, Vadim A. Ферментативні підходи до отримання α-амінофосфонових кислот та фторвмісних β-амінокислот |
| title | Ферментативні підходи до отримання α-амінофосфонових кислот та фторвмісних β-амінокислот |
| title_alt | Enzymatic approaches for preparation of α-aminophosphonic acids and fluorine-containing β-amino acids |
| title_full | Ферментативні підходи до отримання α-амінофосфонових кислот та фторвмісних β-амінокислот |
| title_fullStr | Ферментативні підходи до отримання α-амінофосфонових кислот та фторвмісних β-амінокислот |
| title_full_unstemmed | Ферментативні підходи до отримання α-амінофосфонових кислот та фторвмісних β-амінокислот |
| title_short | Ферментативні підходи до отримання α-амінофосфонових кислот та фторвмісних β-амінокислот |
| title_sort | ферментативні підходи до отримання α-амінофосфонових кислот та фторвмісних β-амінокислот |
| topic | пеніцилін ацилаза енантіоселективне кінетичне розділення гідролітичне діацилювання 1-аміноалкілфосфонові кислоти 1-аміноалкілфосфінові кислоти β-фторалкіл-β-амінокислоти α-алкіл-β-фторалкіл-β-амінокислоти |
| topic_facet | penicillin acylase enantioselective kinetic resolution hydrolytic diacylation 1-aminoalkylphosphonic acids 1-aminoalkyl-phosphinic acids α-alkyl-β-fluoroalkyl-β-amino acids пеніцилін ацилаза енантіоселективне кінетичне розділення гідролітичне діацилювання 1-аміноалкілфосфонові кислоти 1-аміноалкілфосфінові кислоти β-фторалкіл-β-амінокислоти α-алкіл-β-фторалкіл-β-амінокислоти |
| url | https://bioorganica.com.ua/index.php/journal/article/view/81 |
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