Synthesis and antibacterial activity of new dimeric pyridinium chlorides based on 2,2-bis(hydroxymethyl)propane-1,3-diyl spacer

Article abstract of DOI:10.1007/s11172-020-2808-5

New bispyridinium dichlorides based on 2,2-bis(hydroxymethyl)propane-1,3-diyl spacer were synthesized from pentaerythritol, 4-aminopyridine, and carboxylic acids. The resulting biocides possess a high antibacterial effect. The minimal inhibitory concentration (MIC) of these compounds against pathogenic bacteria, namely, gram-positive Methicillin-resistant Staphylococcus aureus (strain ATCC 25923) and gram-negative Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853), was established. The influence of the alkyl substituent length in salts on their microbiological activity was studied.

Full text of DOI:10.1007/s11172-020-2808-5

620
Russian Chemical Bulletin, International Edition, Vol. 69, No. 3, pp. 620—623, March, 2020
Brief Communications
Synthesis and antibacterial activity of new dimeric pyridinium chlorides
based on 2,2-bis(hydroxymethyl)propane-1,3-diyl spacer*
A. N. Vereshchagin, K. A. Karpenko, and M. P. Egorov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
4
7 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6390. Е-mail: vereshchagin@ioc.ac.ru
New bispyridinium dichlorides based on 2,2-bis(hydroxymethyl)propane-1,3-diyl spacer
were synthesized from pentaerythritol, 4-aminopyridine, and carboxylic acids. The resulting
biocides possess a high antibacterial effect. The minimal inhibitory concentration (MIC) of
these compounds against pathogenic bacteria, namely, gram-positive Methicillin-resistant
Staphylococcus aureus (strain ATCC 25923) and gram-negative Escherichia coli (ATCC 25922)
and Pseudomonas aeruginosa (ATCC 27853), was established. The influence of the alkyl sub-
stituent length in salts on their microbiological activity was studied.
Key words: bis-quaternary ammonium compounds, antibacterial agents, pyridinium salts,
pentaerythritol, alkyl chlorides.
Quaternary ammonium compounds have been widely
used as antiseptics and disinfectants since the middle of
even in very low concentrations, against a wide range of
gram-positive and gram-negative bacteria, fungi, and some
1
—3
4—9
the 20th century.
Among them, quaternary bispyri-
viruses.
Typically, these compounds contain two
dinium salts are an important group of chemicals widely
used as biocides due to their strong antimicrobial effect,
pyridine rings bound by a spacer (most often this is a long
aliphatic chain). The rings have alkyl, alkenyl, or alkynyl
substituent (chain) at meta or para positions from the
spacer. Octenidine dihydrochloride 1 is one of the most
efficient dimeric pyridinium salt. Octenidine-based anti-
septic drugs have a damaging effect against a wide range
*
Based on the Materials of the IV Russian Conference on Medical
Chemistry with International Participation (June 9—14, 2019,
Ekaterinburg, Russia).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 0620—0623, March, 2020.
066-5285/20/6903-0620 © 2020 Springer Science+Business Media LLC
1

Antibacterial bispyridinium chlorides
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 3, March, 2020
621
of multiresistant pathogens.10—12 These pathogenic bac-
teria are the causative agents of a wide range of diseases,
including nosocomial ones (tuberculosis, various types of
pneumonia, gastroenteritis, etc.).
the known procedure.16 4-Alkylaminopyridines 5a—f were
synthesized from 4-aminopyridine and carboxylic acids
in three steps using known procedures: 1) conversion of
1
7
carboxylic acid into chloride; 2) reaction of the acid
1
8
The study of the structure—biological activity relation-
ship is one of the modern interdisciplinary approaches
used in organic chemistry.13 It is known that the nature
of the spacer has a significant effect on the manifestation
of biocidal action by dimeric quaternary ammonium
compounds. The work14 proposed an original approach
to the synthesis of several new bispyridinium salts with
oxygen-containing linear branched and cyclic spacers in
the structure based on inexpensive pentaerythritol. It was
found that type 2 compounds containing oxygen atoms in
the cyclic spacer are less toxic than dimeric quaternary
ammonium compounds without oxygen atoms, with their
chloride with 4-aminopyridine; 38) reduction of the re-
1
sulting N-(4-pyridyl)alkanamide.
4-Methylpentan-2-one (methyl isobutyl ketone) was
chosen as a solvent due to the fact that it was successfully
used at the stage of N-alkylation of pyridine derivatives
with alkyl halides in the synthesis of new dimeric quater-
8
,9
nary ammonium compounds. The resulting salts pre-
cipitated from the reaction mixture and were isolated by
simple filtration.
New compounds 3a—f were tested for bacteriostatic
action against resistant pathogenic bacteria: gram-posi-
tive Methicillin-resistant Staphylococcus aureus (MRSA,
strain ATCC 25923) and gram-negative Escherichia coli
15
efficiency being not inferior to that of known antiseptics.
(ATCC 25922) and Pseudomonas aeruginosa (ATCC
27853) (Table 1). Octenidine dihydrochloride (1) and
pentaerythritol-based compound 2 were used as reference
compounds.
The relationship between the length of the alkyl chain
in new dimeric salts 3 and their inhibitory concentration
was established. The high activity (similar to that of the
reference samples) against gram-positive Staphylococcus
aureus was observed for compounds 3b—d with the
Table 1. Minimum inhibitory concentration (MIC) of
compounds 1, 2, and 3a—f
The present work reports the results of the synthesis
and study of the microbiological activity of new dimeric
quaternary pyridinium salts 3 based on 2,2-bis(hydr-
oxymethyl)propane-1,3-diyl spacer. Compounds 3 were
obtained from 2,2-bis(chloromethyl)propane-1,3-diol (4)
and 4-alkylaminopyridines 5 (Scheme 1) by reflux in
Compound
MIC, ppm
MRSA
E. coli
P. aeruginosa
1
2
2
2
4
4
8
32
4
-methylpentan-2-one. The target bispyridinium salts
3a
3b
64
2
128
8
>256
64
3
a—f were obtained in 65—75% yields. 2,2-Bis(chloro-
3
3
3
3
c
d
e
f
2
4
16
methyl)propane-1,3-diol (4) was obtained in two steps
by the reaction of pentaerythritol and thionyl chloride
with subsequent reflux of the resulting cyclic sulfite in an
alcoholic solution of potassium hydroxide according to
2
4
16
64
64
256
>256
4
8
Scheme 1
i. SOCl , then KOH/EtOH; ii. 4-methylpentan-2-one, 118 C, 24 h.
3
a
b
c
n
7
8
9
Yield (%)
3
d
e
f
n
Yield (%)
2
65
71
71
10
11
12
74
70
75

6
22
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 3, March, 2020
Vereshchagin et al.
a white powder, m.p. 168—170 C. 1H NMR (DMSO-d6,
C(8)—C(10) alkyl substituents. Salts 3c and 3d are also
not inferior to octenidine 1 and compound 2 against gram-
negative E.coli. The synthesized compounds 3 are less
efficient against P.aeruginosa than the reference samples.
The best bacteriostatic effect among the new compounds
is possessed by compound 3c (with the n-nonyl group).
An increase or decrease in the length of the alkyl fragment
leads to a decrease in microbiological activity. Thus,
3
00.13 MHz), δ: 0.85 (t, 6 H, 2 CH , J = 7.3 Hz); 1.18—1.40
3
(
m, 16 H, 8 CH ); 1.52—1.64 (m, 4 H, 2 CH ); 3.04 (s, 4 H,
2
2
2
2
8
OCH ); 3.23 (d, 4 Н, 2 NCH , J = 7.0 Hz); 4.18 (s, 4 Н,
2 2
+
N CH ); 5.66 (s, 2 H, 2 OH); 6.84—7.00 (m, 4 H, 4 CH, Py),
2
.06 (d, 2 H, Py, J = 6.6 Hz); 8.16 (d, 2 H, Py, J = 6.6 Hz); 9.00
13
(
(
s, 2 H, 2 NH). C NMR (DMSO-d , 75.47 MHz), δ: 13.9
6
s, 2 С, CH ); 21.9 (s, 2 С, CH ); 26.2 (s, 2 С, CH ); 27.9 (s, 2 С,
3
2
2
CH ); 28.5 (s, 2 С, CH ); 31.0 (s, 2 С, CH ); 42.3 (s, 2 С, NCH );
2
2
2
2
+
compounds 3a (С Н ), 3е (С Н ), and 3f (С Н ) are
47.0 (s, 1 C); 55.6 (s, 2 С, OCH ); 57.5 (s, 2 С, N CH ); 104.9
7
15
11 21
12 25
2
2
noticeably inferior to salts 3b—d in the activity against
MRSA and E.coli and they are inactive against Pseudomonas
aeruginosa.
In conclusion, we synthesized new bis-quaternary am-
monium compounds of the pyridinium series based on
(s, 2 С, Py); 109.9 (s, 2 С, Py); 143.0 (s, 2 С, Py); 144.4 (s, 2 С,
–
1
Py); 156.4 (s, 2 C, Py). IR (KBr), /cm : 3428, 3208, 2968,
1
2
656, 1554, 1466, 1360, 1224, 1192, 848. MS (ESI): found m/z
2
+
43.1980 [М – 2 Cl] ; calculated for C H Cl N O 243.1967.
2
9
50
2
4
2
1
,1´-[2,2-Bis(hydroxymethyl)propane-1,3-diyl]bis(4-octyl-
aminopyridinium) dichloride (3b). The yield was 0.83 g (71%),
2
,2-bis(hydroxymethyl)propane-1,3-diyl spacer, which
have pronounced antibacterial properties. Six salts with
the length of the alkyl substituent from C H to C H
1
a white powder, m.p. 158—160 C. H NMR (DMSO-d6,
00.13 MHz), δ: 0.85 (t, 6 H, 2 CH , J = 7.3 Hz); 1.18—1.40
3
3
(m, 20 H, 10 CH ); 1.50—1.62 (m, 4 H, 2 CH ); 3.02 (s, 4 H,
7
15
12 25
2
2
were obtained in 65—75% yields. The best MIC values
against gram-positive Staphylococcus aureus and gram-
negative Escherichia coli and Pseudomonas aeruginosa were
2 OCH ); 3.25 (d, 4 Н, 2 NCH , J = 7.0 Hz); 4.18 (s, 4 Н,
2
2
+
2
8
N CH ); 5.70 (s, 2 H, 2 OH); 6.88—7.00 (m, 4 H, 4 CH, Py);
.05 (d, 2 H, Py, J = 6.6 Hz); 8.18 (d, 2 H, Py, J = 6.6 Hz); 8.98
2
1
3
(
(
s, 2 H, 2 NH). C NMR (DMSO-d , 75.47 MHz), δ: 13.9
6
shown by the compound with an alkyl substituent C H .
9
19
s, 2 С, CH ); 22.0 (s, 2 С, CH ); 26.3 (s, 2 С, CH ); 27.9 (s, 2 С,
3
2
2
This compound is comparable in microbiological activity
with the known antibacterial agent octenidine dihydro-
chloride. An increase or decrease in the length of the alkyl
substituent leads to a decrease in the microbiological effect.
CH ); 28.5 (s, 2 С, CH ); 28.6 (s, 2 С, CH ); 31.1 (s, 2 С, CH );
2
2
2
2
4
(
2.2 (s, 2 С, NCH ); 46.8 (s, 1 C); 55.8 (s, 2 С, OCH ); 57.3
2
2
+
s, 2 С, N CH ); 104.8 (s, 2 С, Py); 109.9 (s, 2 С, Py); 142.5
2
(s, 2 С, Py); 144.9 (s, 2 С, Py); 156.7 (s, 2 C, Py). IR (KBr),
–
1

/cm : 3423, 3210, 2968, 1656, 1560, 1463, 1362, 1224, 1192,
50. MS (ESI): found m/z 257.2131 [М – 2 Cl] ; calculated for
2
+
8
Experimental
C31H54Cl N O 257.2123.
2
4
2
1
,1´-[2,2-Bis(hydroxymethyl)propane-1,3-diyl]bis(4-nonyl-
1Н and 13C NMR spectra were recorded on a Bruker AM-300
spectrometer (300.13 MHz and 75.47 MHz, respectively).
Electrospray ionization (ESI) high-resolution mass spectra were
recorded on a Bruker micrOTOF II instrument. IR spectra were
recorded in KBr tablets on a Specord M82 Fourier-transform
spectrometer with Soft Spectra software. Melting points were
obtained on a Gallenkamp apparatus. Thin layer chromatography
was performed on precoated DC Kieselgel 60 F254 silica gel on
aluminum plates.
aminopyridinium) dichloride (3c). The yield was 0.87 g (71%),
1
a white powder, m.p. 152—155 C. H NMR (DMSO-d6,
300.13 MHz), δ: 0.85 (t, 6 H, 2 CH , J = 7.3 Hz); 1.18—1.40
3
(m, 24 H, 12 CH ); 1.48—1.64 (m, 4 H, 2 CH ); 3.00 (s, 4 H,
2
2
2 OCH ); 3.28 (d, 4 Н, 2 NCH , J = 7.0 Hz); 4.20 (s, 4 Н,
2
2
+
2 N CH ); 5.68 (s, 2 H, 2 OH); 6.86—7.02 (m, 4 H, 4 CH, Py);
2
8.02 (d, 2 H, Py, J = 6.6 Hz); 8.21 (d, 2 H, Py, J = 6.6 Hz); 9.02
1
3
(s, 2 H, 2 NH). C NMR (DMSO-d , 75.47 MHz), δ: 13.8
6
(s, 2 С, CH ); 21.9 (s, 2 С, CH ); 26.3 (s, 2 С, CH ); 27.9 (s, 2 С,
3
2
2
2
,2-Bis(chloromethyl)propane-1,3-diol (4) and 4-alkylami-
CH ); 28.1 (s, 2 С, CH ); 28.5 (s, 2 С, CH ); 28.7 (s, 2 С, CH );
2 2 2 2
1
6—18
nopyridines 5a—f were obtained using known procedures.
31.0 (s, 2 С, CH ); 42.2 (s, 2 С, NCH ); 46.7 (s, 1 C); 55.8
2 2
+
Microbiological test. Test samples were prepared at a con-
centration of 20,000 ppm with ethanol, an aliquot (150 μL) was
transferred using an Eppendorf tube and diluted in two steps
with a liquid nutrient medium (to a final concentration of
(s, 2 С, OCH ); 57.3 (s, 2 С, N CH ); 104.7 (s, 2 С, Py); 110.0
2
2
(s, 2 С, Py); 142.6 (s, 2 С, Py); 144.7 (s, 2 С, Py); 157.0 (s, 2 C,
–
1
Py). IR (KBr), /cm : 3434, 3200, 2964, 1656, 1560, 1468,
1362, 1224, 1192, 850. MS (ESI): found m/z 271.2291 [М – 2 Cl]2+
;
2
56—0.25 ppm). An aliquot (150 μL) was added into a 96-well
calculated for C33H58Cl N O 271.2280.
2 4 2
6
–1
plate. Then a 10 CFU mL aliquot of bacteria (150 μL) was
added. The MICs were determined visually based on turbidity
after incubation for 24 h at 37 C.
1,1´-[2,2-Bis(hydroxymethyl)propane-1,3-diyl]bis(4-decyl-
aminopyridinium) dichloride (3d). The yield was 0.95 g (74%),
1
a white powder, m.p. 165—168 C. H NMR (DMSO-d6,
Synthesis of bispyridinium salts 3a—f (general procedure).
A mixture of 2,2-bis(chloromethyl)propane-1,3-diol (4) (0.346 g,
300.13 MHz), δ: 0.85 (t, 6 H, 2 CH , J = 7.3 Hz); 1.18—1.40
3
(m, 24 H, 12 CH ); 1.48—1.64 (m, 4 H, 2 CH ); 3.00 (s, 4 H,
2
2
2
mmol) and 4-alkylaminopyridine 5a—f (4 mmol) was refluxed
2 OCH ); 3.28 (d, 4 Н, 2 NCH , J = 7.0 Hz); 4.20 (s, 4 Н,
2
2
+
in 4-methylpentan-2-one (4 mL) for 24 h. The reaction comple-
tion was determined by TLC (hexane—ethyl acetate (3 : 1)) based
on the disappearance of spots of 4-alkylaminopyridines 5a—f.
The mixture was cooled and allowed to stand at 0 C for 30 min.
The precipitate was collected by filtration and dried to obtain
pure products 3a—f.
2 N CH ); 5.68 (s, 2 H, 2 OH); 6.86—7.02 (m, 4 H, 4 CH, Py);
2
8.02 (d, 2 H, Py, J = 6.6 Hz); 8.21 (d, 2 H, Py, J = 6.6 Hz); 9.02
1
3
(s, 2 H, 2 NH). C NMR (DMSO-d , 75.47 MHz), δ: 13.8
6
(s, 2 С, CH ); 21.9 (s, 2 С, CH ); 26.3 (s, 2 С, CH ); 27.9 (s, 2 С,
3
2
2
CH ); 28.1 (s, 2 С, CH ); 28.5 (s, 2 С, CH ); 28.7 (s, 2 С, CH );
2
2
2
2
28.9 (s, 2 С, CH ); 31.2 (s, 2 С, CH ); 42.2 (s, 2 С, NCH ); 46.7
2
2
2
+
1
,1´-[2,2-Bis(hydroxymethyl)propane-1,3-diyl]bis(4-heptyl-
(s, 1 C); 55.8 (s, 2 С, OCH ); 57.3 (s, 2 С, N CH ); 104.7 (s, 2 С,
2
2
aminopyridinium) dichloride (3а). The yield was 0.72 g (65%),
Py); 110.0 (s, 2 С, Py); 142.6 (s, 2 С, Py); 144.7 (s, 2 С, Py);

Antibacterial bispyridinium chlorides
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 3, March, 2020
623
1
1
57.0 (s, 2 C, Py). IR (KBr), /cm–1: 3438, 3204, 2968, 1656,
References
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560, 1468, 1360, 1224, 1190, 848. MS (ESI): found m/z 285.2424
+
[
М – 2 Cl]2 ; calculated for C35H62Cl N O 285.2436.
2
4
2
1
2
1
,1´-[2,2-Bis(hydroxymethyl)propane-1,3-diyl]bis(4-undecyl-
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3
4
1
. D. M. Bailey, C. G. DeGrazia, S. J. Hoff, P. L. Schulenberg,
3
00.13 MHz), δ: 0.84 (t, 6 H, 2 CH , J = 7.3 Hz); 1.16—1.42
3
J. R. O´Connor, D. A. Paris, A. M. Slee, J. Med. Chem.,
(
m, 28 H, 14 CH ); 1.48—1.62 (m, 4 H, 2 CH ); 2.97 (s, 4 H,
2
2
1984, 27, 1457.
2
2
8
OCH ); 3.30 (d, 4 Н, 2 NCH , J = 7.0 Hz); 4.18 (s, 4 Н,
2 2
5
6
. H. Kourai, T. Yabuhara, A. Shirai, T. Maeda, H. Nagamune,
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N CH ); 5.70 (s, 2 H, 2 OH); 6.86—7.04 (m, 4 H, 4 CH, Py);
2
.00 (d, 2 H, Py, J = 6.6 Hz); 8.18 (d, 2 H, Py, J = 6.6 Hz); 9.06
1
3
(
(
s, 2 H, 2 NH). C NMR (DMSO-d , 75.47 MHz), δ: 13.6
6
s, 2 С, CH ); 21.9 (s, 2 С, CH ); 26.2 (s, 2 С, CH ); 27.8 (s, 2 С,
3
2
2
7. D. Obando, Y. Koda, N. Pantarat, S. Lev, X. Zuo, J. B. Oei,
CH ); 28.1 (s, 2 С, CH ); 28.5 (s, 2 С, CH ); 28.7 (s, 4 С, CH );
2
2
2
2
F. Widmer, J. T. Djordjevic, T. C. Sorell, K. A. Jolliffe,
ChemMedChem, 2018, 13, 1421.
2
(
8.9 (s, 2 С, CH ); 31.4 (s, 2 С, CH ); 42.0 (s, 2 С, NCH ); 46.5
2 2 2
+
s, 1 C); 55.6 (s, 2 С, OCH ); 57.1 (s, 2 С, N CH ); 104.8 (s, 2 С,
2
2
8
9
. A. N. Vereshchagin, A. M. Gordeeva, N. A. Frolov, P. I.
Proshin, K. A. Hansford, M. P. Egorov, Eur. J. Org. Chem.,
Py); 109.9 (s, 2 С, Py); 142.5 (s, 2 С, Py); 144.6 (s, 2 С, Py);
–
1
1
1
[
57.2 (s, 2 C, Py). IR (KBr), /cm : 3444, 3198, 2968, 1660,
2
019, 4123.
564, 1468, 1360, 1224, 1192, 848. MS (ESI): found m/z 299.2600
. A. N. Vereshchagin, N. A. Frolov, V. Y. Konyuhova, K. A.
М – 2 Cl]2 ; calculated for C37H66Cl N O 299.2593.
+
2
4
2
Hansford, M. P. Egorov, Mendeleev Commun., 2019, 29, 523.
1
,1´-[2,2-Bis(hydroxymethyl)propane-1,3-diyl]bis(4-dodecyl-
1
0. E. Küng, J. Pietrzak, C. Klaus, J. Walochnik, Int. J. Anti-
aminopyridinium) dichloride (3f). The yield was 1.04 g (75%),
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microb. Agents, 2016, 47, 232.
1
1
1. R. Alvarez-Marin, M. Aires-de-Sousa, P. Nordmann,
3
00.13 MHz), δ: 0.84 (t, 6 H, 2 CH , J = 7.3 Hz); 1.16—1.46
3
N. Kieffer, L. Poirel, Eur. J. Clin. Microbiol. Infect. Dis., 2017,
(
m, 32 H, 16 CH ); 1.50—1.64 (m, 4 H, 2 CH ); 2.97 (s, 4 H,
2
2
3
6, 2379.
2
2
7
OCH ); 3.28 (d, 4 Н, 2 NCH , J = 7.0 Hz); 4.14 (s, 4 Н,
2 2
1
2. A. Obermeier, J. Schneider, N. Harrasser, J. Tubel1, H. Muhl-
+
N CH ); 5.74 (s, 2 H, 2 OH); 6.88—7.04 (m, 4 H, 4 CH, Py);
2
hofer, D. Pforringer, C. von Deimling, P. Foehr, B. Kiefel,
C. Kramer, A. Stemberger, M. Schieker, R. Burgkart, R. von
Eisenhart-Rothe, PLoS One, 2018, 13, e0190912.
.96 (d, 2 H, Py, J = 6.6 Hz); 8.14 (d, 2 H, Py, J = 6.6 Hz); 9.02
1
3
(
(
s, 2 H, 2 NH). C NMR (DMSO-d , 75.47 MHz), δ: 13.5
6
s, 2 С, CH ); 22.0 (s, 2 С, CH ); 26.3 (s, 2 С, CH ); 27.8 (s, 2 С,
3
2
2
1
1
3. A. N. Vereshchagin, Russ. Chem. Bull., 2017, 66, 1765.
CH ); 28.1 (s, 2 С, CH ); 28.5 (s, 2 С, CH ); 28.6 (s, 2 С, CH );
2
2
2
2
4. Y. Tsuji, M. Yamamoto, A. N. Vereshchagin, A. S. Dorofeev,
T. A. Geyvandova, I. F. Agafonova, R. K. Geyvandov, Pat.
WO158045, 2014.
2
8.7 (s, 4 С, CH ); 28.9 (s, 2 С, CH ); 31.3 (s, 2 С, CH ); 42.1
2 2 2
(
s, 2 С, N—CH ); 46.3 (s, 1 C); 55.4 (s, 2 С, OCH ); 57.0 (s, 2 С,
2
2
+
N CH ); 104.6 (s, 2 С, Py); 109.7 (s, 2 С, Py); 142.3 (s, 2 С,
2
1
5. M. Yamamoto, T. Takami, R. Matsumura, A. Dorofeev,
–
1
Py); 144.4 (s, 2 С, Py); 157.0 (s, 2 C, Py). IR (KBr), /cm
:
Y. Hirata, H. Nagamune, Biocontrol Sci., 2016, 21, 231.
3
440, 3210, 2972, 1664, 1560, 1468, 1360, 1224, 1190, 850.
1
6. A. Mooradin, J. B. Cloke, J. Am. Chem. Soc., 1945, 67, 942.
2
+
MS (ESI): found m/z 313.2756 [М – 2 Cl] ; calculated for
C39H70Cl N O 313.2749.
1
7. Y. Zhao, V. Snieckus, Org. Lett., 2014, 16, 390.
8. E. J. Delaney, L. E. Wood, I. M. Klotz, J. Am. Chem. Soc.,
982, 104, 799.
2
4
2
1
1
This work was financially supported by the President
of the Russian Federation Council for Grants (Program
for State Support of Young Scientists of Russia, Grant
MD-545.2019.3).
Received November 11, 2019;
accepted January 14, 2020