Synthesis and fungicidal activity of methylsulfanylmethyl ether derivatives of levoglucosenone

Article abstract of DOI:10.1007/s10593-019-02415-7

[Figure not available: see fulltext.] A series of derivatives were synthesized on the basis of levoglucosenone that contained hydroxy groups at the С-4 atom or С-2 and С-4 atoms or a hydroxy and methyl group at the С-4 atom. In addition, 4-hydroxymethylbutanolides were synthesized. Derivatives containing hydroxy groups were obtained as methylsulfanylmethyl ethers. It was established that compounds containing a 6,8-dioxabicyclo[3.2.1]-octane ring exhibited fungicidal activity against Rhizoctonia solani. It was shown that the presence of a methylsulfanylmethyl moiety in the ring could increase the fungicidal activity of compounds.

Full text of DOI:10.1007/s10593-019-02415-7

DOI 10.1007/s10593-019-02415-7
Chemistry of Heterocyclic Compounds 2019, 55(1), 31–37
Synthesis and fungicidal activity of methylsulfanylmethyl
ether derivatives of levoglucosenone
Bulat T. Sharipov1*, Anna N. Davidova1, Alena S. Ryabova2,
Nailya F. Galimzyanova2, Farid A. Valeev1
1
Ufa Institute of Chemistry, Russian Academy of Sciences,
71 Oktyabrya Ave., Ufa 450054, Russia; e-mail: sharipovbt@anrb.ru
2
Ufa Institute of Biology, Russian Academy of Sciences,
69 Oktyabrya Ave., Ufa 450054, Russia; e-mail: galnailya@yandex.ru.
Submitted December 6, 2018
Accepted January 16, 2019
Translated from Khimiya Geterotsiklicheskikh Soedinenii,
2019, 55(1), 31–37
A series of derivatives were synthesized on the basis of levoglucosenone that contained hydroxy groups at the С-4 atom or С-2 and С-4
atoms or a hydroxy and methyl group at the С-4 atom. In addition, 4-hydroxymethylbutanolides were synthesized. Derivatives containing
hydroxy groups were obtained as methylsulfanylmethyl ethers. It was established that compounds containing a 6,8-dioxabicyclo[3.2.1]-
octane ring exhibited fungicidal activity against Rhizoctonia solani. It was shown that the presence of a methylsulfanylmethyl moiety in
the ring could increase the fungicidal activity of compounds.
Keywords: γ-butanolides, levoglucosenone, methylthiomethyl ethers, fungicidal activity, Rhizoctonia solani.
Levoglucosenone is a unique compound with advan-
tages compared to other materials that are obtained from
renewable biological sources: it is readily available via
pyrolysis of any cellulose-containing materials. The
structure of levoglucosenone combines 6,8-dioxabicyclo-
[3.2.1]octane framework with an enone system, keto group,
and an acetal center. The 1,6-anhydro bridge blocks the
acetal center and sterically shields the molecule, providing
regio- and stereoselectivity. All of these features combined
in one molecule make levoglucosenone a convenient chiral
starting material for practical synthesis of various
enantiomerically pure derivatives that are used in the
chemistry of natural compounds.1 A wide range of
biologically active natural compounds and their analogs
have been synthesized on the basis of levoglucosenone:
carbohydrates,2 nucleosides,3 γ-butyrolactones,4 pheromo-
nes,5 and prostaglandins.6 In several cases the levo-
glucosenone molecule was modified in order to obtain
compounds with practically useful biological properties:
cytotoxic activity,7 antimicrobial8 and herbicidal effects.9
Recent progress in the use of levoglucosenone deri-
vatives as alternative industrial solvents for the
replacement of toxic solvents points to the great promise of
such renewable chemicals not only in laboratory-scale
syntheses but also for industrial applications.10
In the current work, we present the results achieved in
the synthesis of levoglucosenone derivatives, among which
hydroxy derivatives protected with a methylsulfanylmethyl
group showed a new type of biological effect – fungicidal
activity against the microscopic fungi Bipolaris soro-
kiniana, Fusarium oxysporum, and Rhizoctonia solani.
We applied several practical methods for the modi-
fication of levoglucosenone (1): oxa-Michael reaction,
1,2-alkylation, and keto group reduction. It should be noted
that dihydrolevoglucosenone (Cyreneтм) (2)) is easily
prepared by hydrogenation11 and is commercially available.
It is known that levoglucosenone (1) can be stereo- and
regioselectively reduced with NaBH4 in aqueous medium,
leading to the formation of carbinol 312 (Scheme 1).
Diastereomerically pure alcohol 4 was obtained by
0009-3122/19/55(1)-0031©2019 Springer Science+Business Media, LLC
31

Chemistry of Heterocyclic Compounds 2019, 55(1), 31–37
Table 1. Baeyer–Villiger oxidation of Cyrene (2) and
selective reduction of Cyrene (2) using baker's yeast
(Saccharomyces cerevisiae).13 A Michael reaction was
performed by maintaining levoglucosenone (1) in water in
the presence of Et3N for 2 h, resulting in hydroxy ketone
5.12 We used this reaction in a one-pot procedure where
hydroxy ketone 5 obtained by hydration of levogluco-
senone (1) was immediately reduced with NaBH4 in
aqueous medium, giving diols 6а,b.
levoglucosenone (1)*
Com-
pound
Catalyst
(amount)
Temperature, Time, Yield,
Solvent
°С
h
%
р-TsOH (1 mol)
i-PrOH
80
2
85
2
2
2
2
2
2
2
1
1
Scheme 1
Amberlyst 15 (1 mol) i-PrOH
25
25
25
50
50
50
50
50
48
48
48
1
44
46
Amberlyst 15 (1 mol)
Amberlyst 15 (2 mol)
Amberlyst 15 (2 mol)
Amberlyst 15 (2 mol)
H2O
H2O
–
O
O
O
O
NaBH4, H2O
68
0°C, 15 min
81%
87
OH
O
O
1
3
H2O
1
87
O
O
Saccharomyces cerevisiae
O
Amberlyst-15 (2 mol) H2O
Amberlyst-15 (2 mol) H2O
2
84**
76
D-glucose, 30°C, H2O, 24 h
99%
1
O
OH
O
2
4
Amberlyst 15 (2 mol)
H2O
2
70**
* Reaction conditions: 10 mmol of ketone 1 or 2, 50 mmol Н2О2.
** Reaction conditions: 10 mmol of ketone 1 or 2, 10 mmol Н2О2.
O
O
O
1) H2O, Et3N, rt, 2 h
H2O
Et3N
1
2) NaBH4, H2O, 1 h
90%
HO
OH
HO
O
In order to improve the yield of butanolide 9, we
performed the reaction at 50°С without adding solvent. The
product was formed in 87% yield already after 1 h, but the
process could not be controlled due to its highly
exothermic nature. Diluting the reaction mixture with water
in 1:1 ratio enabled better control of the reaction without
decreasing the yields.
Using an excess of H2O2 was effective for achieving
complete conversion, but required neutralization of residual
reagent in order to prevent explosion during workup of the
reaction mixture. In order to decrease the residual amount
of H2O2, we studied oxidation using 1 equiv of 30% H2O2.
This change resulted in a slight decrease of conversion and
yield but allowed to nearly completely avoid the need for
H2O2 neutralization step.
Baeyer–Villiger oxidation of levoglucosenone (1) in
i-PrOH in the presence of р-TsOH led to the formation of
complex product mixture. Oxidation of levoglucosenone
(1) with 5 equiv of 30% H2O2 in aqueous medium in the
presence of Amberlyst 15 resin provided lactone 10 in 76%
yield (Table 1). Using equimolar amounts of oxidizing
agent gave lactone 10 in 70% yield. It should be noted that
epimerization at the С-5 carbon atom did not occur under
these conditions.
The further direction of work involved protecting the
free hydroxy groups in compounds obtained above as
methylsulfanylmethyl ethers. This transformation can be
achieved using DMSO–Ac2O,14,18 DMSO–Ac2O–АсОН,19
and Me2S–(PhCO2)2–MeCN20 systems. Synthesis of
methylsulfanylmethyl ether 11 was performed in
quantitative yield by heating alcohol 7 in Ac2O–DMSO
system to 40°С (Scheme 3).14 The saturated product 12 was
obtained analogously.
5
6a,b
6b:6a = 5:1
The reaction of levoglucosenone (1) with MeMgI in
CH2Cl2–Еt2O system was used to synthesize alcohol 714
(Scheme 2). Since similar methylation of Cyrene (2)
resulted in a mixture of products,11b,15 the saturated alcohol
8 was obtained by hydrogenation of alcohol 7 in the
presence of Raney nickel catalyst.
Scheme 2
O
7
1
O
O
O
MeMgI
H2, Ni Raney
5
1
4
OH
OH
EtOAc, rt, 48 h
89%
2
3
Me
7
Me
8
Another short route for the modification of levogluco-
senone derivatives involves Baeyer–Villiger oxidation that
leads to butan-4-olides containing a primary hydroxy-
methyl group protected by a formyl group.16 Previously we
developed an effective method for Baeyer–Villiger
oxidation of Diels–Alder adducts obtained from levogluco-
senone (1) and 1,3-dienes, giving deprotected γ-butanolides
in one step by refluxing the adducts with 30% H2O2 and
acids in i-PrOH.17 We studied the oxidation reaction of
Cyrene 2 with 30% H2O2 in the presence of р-TsOH, which
led to the formation of butanolide 9 in 85% yield (Table 1).
The well-known acidic catalyst Amberlyst 15 has been
used for the hydrolysis of formyl group in γ-butanolides16b,c
and was able to promote the oxidation of Cyrene (2) at
room temperature. When the reaction was performed in
i-PrOH over 2 days, the yield of deprotected product 9 was
44%. The reaction proceeded analogously also in aqueous
medium. Doubling the amount of Amberlyst 15 allowed to
increase the yield of butanolide 9 to 68% while using the
same reaction duration.
The protection of hydroxy group in alcohol 4 was
performed in DMSO–Ac2O system, leading to the
formation of the desired ether 13 as well as acetate 14 and a
byproduct from the oxidation of Cyrene (2) (Scheme 4).
Using DMSO–Ac2O–АсОН system, which is commonly
32

Chemistry of Heterocyclic Compounds 2019, 55(1), 31–37
Scheme 3
Scheme 5
employed in similar cases,19 gave ether 13 in 67% yield.
The reaction of DMSO with allyl alcohol 3 under these
conditions increased the yield of levoglucosenone (1)
oxidation product to 32%, while the yield of the desired
ether 15 was 36%. The attempt to synthesize methyl-
thiomethyl ether from alcohol 5 resulted in dehydration,
giving levoglucosenone (1) in 76% yield. For the purpose
of increasing the yield of ethers 13 and 15 we tested a
method where alcohols were treated with Me2S in the
presence of (PhCO2)2. As a result, alcohols 4 and 3 were
converted to ethers 13 and 15 in 74 and 71% yields,
respectively.
Table 2. The effects of compounds on the development of fungal
test cultures (aerial mycelium development suppression in the
zone of compound action, mm)
Com-
pound
Rhizoctonia
solani
Bipolaris
sorokiniana
Fusarium
oxysporum
13.0 3.0
31.6 3.2
13.0 1.0
14.0 3.0
13.3 0.7
1
7
Delay in fungal
development
No growth of
micromycetes
Delay in fungal
development
15.0 3.0
11
Scheme 4
–*
–
–
–
12
13
30.1 4.7
Delay in fungal
development
No growth of
micromycetes
No growth of
micromycetes
No growth of
micromycetes
No growth of
micromycetes
–
–
–
–
–
–
–
15
17
18
19
No growth of
micromycetes
* No activity or insignificant zone of growth suppression.
activity against the microscopic fungus Bipolaris
sorokiniana, suppressing its development. The rest of the
methylthiomethyl ethers showed different levels of
Synthesis of bismethylsulfanylmethyl ether 17 was fungistatic activity against Bipolaris sorokiniana and
achieved starting from 2S-isomer 6а using Me2S–(PhCO2)2 Fusarium oxysporum.
mixture (Scheme 5). The hydroxy groups of γ-butanolides
Remarkably, compounds not containing sulfur, such as
9 and 10 were also protected using Me2S. The reaction in levoglucosenone (1) and alcohol 7, also suppressed the
both cases proceeded easily, with the formation of ethers growth of microscopic fungi, while the saturated ether 12
18 and 19 in 83 and 80% yields, respectively. It should be bearing a methyl group at the С-4 carbon atom was the
noted that this method was more effective for the least active among the tested compounds.
protection of hydroxy groups in γ-butanolide 9, compared
In addition, testing according to analogous method
to the previously described synthesis using chloromethyl revealed bactericidal activity of levoglucosenone (1) at
methyl sulfide where the yield of product 18 was only 0.5% concentration against actinobacteria Streptomyces
46%.21
xanthophaeus and Streptomyces atroolivaceus.
All methylsulfanylmethyl derivatives 11–13, 15, 17–19,
Thus, compounds containing 6,8-dioxabicyclo[3.2.1]-
levoglucosenone (1), and alcohol 7 were tested for octane ring in their structures may exhibit fungicidal
fungicidal activity against the microscopic fungi activity against Rhizoctonia solani and fungistatic effects
Rhizoctonia solani, Bipolaris sorokiniana, and Fusarium on micromycetes Bipolaris sorokiniana and Fusarium
oxysporum that affect agricultural crops (Table 2). The oxysporum. The presence of methylsulfanylmethyl group in
compounds were tested as 0.5% solutions in DMF.
molecule can result in enhanced fungicidal activity of these
The results of biological testing allowed to conclude that compounds.
the majority of the studied compounds at 0.5%
concentration showed pronounced fungicidal activity
Experimental
IR spectra were recorded for Nujol mulls on Shimadzu
against Rhizoctonia solani, resulting in nearly complete
growth suppression. Lactone 19 exhibited fungicidal IR Prestige-21 and Bruker Tensor 27 spectrometers. 1Н and
33

Chemistry of Heterocyclic Compounds 2019, 55(1), 31–37
13С NMR spectra were acquired on a Bruker Avance III
(c 1.0, CHCl3), [α]D –132.8° (c 1.0, H2O) (mp ~28°С (not
sharp), [α]D25 –133° (c 0.6, H2O)22). Rf 0.3 (petroleum ether –
EtOAc, 1:1). IR spectrum, ν, cm–1: 3418, 1131, 1070, 985,
500 MHz spectrometer (500 and 125 MHz, respectively)
for CDCl3 solutions (the use of other solvents is indicated
in each separate case), internal standard – residual solvent
1
900. H NMR spectrum, δ, ppm (J, Hz): 1.49 (1Н, dtd,
1
signals (CDCl3: 7.27 ppm for Н nuclei, 77.1 ppm for 13С
J = 12.9, J = 10.0, J = 6.1, 3-СНendo); 1.57 (1Н, dd,
J = 13.9, J = 6.1) and 1.82–1.91 (1Н, m, 2-СН2); 1.98–2.04
(1Н, m, 3-СНexo); 2.18 (1Н, br. s, OH); 3.58 (1Н, dd,
J = 10.0, J = 6.2, 4-СН); 3.79 (1Н, dd, J = 7.1, J = 5.4) and
3.83 (1Н, d, J = 7.1, 7-СН2); 4.46–4.49 (1Н, m, 1-СН);
5.30 (1Н, s, 5-СН). 13C NMR spectrum, δ, ppm: 26.0
(C-3); 27.8 (C-2); 68.2 (C-7); 70.0 (C-4); 72.8 (C-1); 102.9
(C-5). Mass spectrum, m/z (Irel, %): 131 [M+H]+ (100).
Found, %: С 55.45; Н 7.79. С6Н10О3. Calculated, %:
С 55.37; Н 7.74.
1
nuclei; CD3OD: 3.30 ppm for Н nuclei, 49.0 ppm for 13С
nuclei). The majority of 13С NMR spectra were acquired in
DEPT or J-MOD modes. In the case of compound 4,
additional two-dimensional COSY, 1Н–13С HSQC,
and NOESY spectra were acquired. Mass spectra were
recorded on
a
Shimadzu LCMS-2010 EV single
quadrupole mass spectrometer in positive and negative ion
modes at 4.5 and –3.5 kV capillary potentials, respectively,
using electrospray ionization, the eluent was MeCN–Н2О
system (MeOH–Н2О system was used as eluent for
compound 19). Elemental analysis was performed on a
EuroVector EA2000 СНNS(O)-analyzer. The optical
rotation angles were measured on a PerkinElmer-341
polarimeter. Melting points were determined on a Boetius
apparatus equipped with an RNMK 05 viewing adapter. TLC
analysis was performed on Sorbfil PTSKh-AF-A plates
(Sorbpolymer, Russia). Column chromatography was
performed on Silica gel 60 from Macherey-Nagel (particle
size 0.063–0.2 mm).
(1R,2S,4S,5R)-6,8-Dioxabicyclo[3.2.1]octane-2,4-diol
(6а) and (1R,2S,4R,5R)-6,8-dioxabicyclo[3.2.1]octane-
2,4-diol (6b). A solution of levoglucosenone (1) (1.00 g,
7.93 mmol) and triethylamine (0.55 ml, 3.96 mmol) in H2O
(60 ml) was stirred at room temperature for 2 h. The
mixture was then treated with 98% NaBH4 (0.31 g,
7.93 mmol) and stirred for approximately 1 h. The excess
of NaBH4 was decomposed with AcOH (3 ml). The solvent
was removed by evaporation on rotary evaporator, the
residue (mixture of alcohols 6а,b) was separated
chromatographically, eluent EtOAc.
Alcohols 512 and 714 were obtained according to
published procedures.
Compound 6а. Yield 0.87 g (75%), white amorphous
20
20
(1S,4S,5R)-6,8-Dioxabicyclo[3.2.1]oct-2-en-4-ol (3).
A
material, [α]D –156° (c 1.0, H2O) ([α]D –156° (c 0.73,
H2O)23). Rf 0.2 (EtOAc). IR spectrum, ν, cm–1: 3374, 1181,
1091, 971, 902. 1H NMR spectrum (СD3OD), δ, ppm
(J, Hz): 1.70 (1Н, ddd, J = 14.3, J = 10.7, J = 4.5) and 1.91
(1Н, dddd, J = 14.3, J = 6.0, J = 3.1, J = 1.7, 3-СН2); 3.71
(1Н, dd, J = 7.6, J = 5.5) and 3.76 (1Н, d, J = 7.6, 7-СН2);
3.74–3.80 (1Н, m, 2-СН); 3.79 (1Н, ddd, J = 10.7, J = 6.0,
J = 1.1, 4-СН); 4.36–4.40 (1Н, m, 1-СН); 5.22 (1Н, s,
5-СН). 13C NMR spectrum (СD3OD), δ, ppm: 32.6 (C-3); 66.0
(C-7); 66.1 (C-4); 67.4 (C-2); 76.6 (C-1); 102.8 (C-5). Mass
spectrum, m/z (Irel, %): 188 [M+MeCN+H]+ (100). Found, %:
С 49.43; Н 6.83. С6Н10О4. Calculated, %: С 49.31; Н 6.90.
Compound 6b. Yield 0.17 g (15%), white amorphous
solution of levoglucosenone (1) (1.00 g, 7.93 mmol) in
H2O (20 ml) was cooled to 0°С and treated by the addition
of 98% NaBH4 (0.31 g, 7.93 mmol). The excess of NaBH4
was destroyed after 15 min by adding acetone (2 ml). The
aqueous layer was extracted with CHCl3, the organic layers
were combined and dried over anhydrous MgSO4. The
solvent was removed by distillation, the residue was
separated chromatographically using petroleum ether –
EtOAc as eluent, gradient from 2:1 to 1:1. Yield 0.82 g
20
(81%), mp 67–68°C, [α]D
–33.7°(c 1.0, CHCl3).
Recrystallization from petroleum ether – СH2Cl2 system
gave crystals with mp 70–71°C, [α]D20 –29.4 (c 1.0, CHCl3)
(mp 70–70.5°C, [α]D20 –30° (CHCl3)12). Rf 0.35 (petroleum
ether – EtOAc, 1:1). 1H NMR spectrum, δ, ppm (J, Hz): 2.55
(1Н, br. s, OH); 3.67 (1Н, dd, J = 6.6, J = 4.2) and 3.78
(1Н, d, J = 6.6, 7-СН2); 4.25 (1Н, br. s, 4-СН); 4.58 (1Н, t,
J = 4.2, 1-СН); 5.43 (1Н, d, J = 2.0, 5-СН); 5.63 (1Н, dt,
J = 9.9, J = 2.1, 3-СН); 6.04 (1Н, dd, J = 9.9, J = 4.2,
2-СН). 13C NMR spectrum, δ, ppm: 68.7 (С-7); 70.7 (С-1);
71.1 (С-4); 101.3 (С-5); 129.1, 130.6 (С-2,3). Mass
spectrum, m/z (Irel, %): 129 [M+H]+ (100). Found, %:
С 56.31; Н 6.36. С6Н8О3. Calculated, %: С 56.24; Н 6.29.
24
20
material, [α]D –78° (c 0.5, H2O) ([α]D –79.9° (H2O)24).
Rf 0.25 (EtOAc). IR spectrum, ν, cm–1: 3370, 1179, 1091,
975, 905. H NMR spectrum (СD3OD), δ, ppm (J, Hz):
1
1.74 (1Н, d, J = 16.2) and 2.13 (1Н, dt, J = 16.2, J = 4.8,
3-СН2); 2.15 (1Н, br. s, OH); 3.65–3.68 (1Н, m, 2-СН);
3.78–3.86 (2Н, m, 7-СНexo, 4-СН); 3.91 (1Н, d, J = 7.9,
7-СНendo); 3.96 (1Н, br. s, OH); 4.57–4.62 (1Н, m, 1-СН);
5.41 (1Н, s, 5-СН). 13C NMR spectrum (D2O), δ, ppm: 29.5
(C-3); 65.3 (C-7); 65.7, 65.9 (C-2,4); 77.0 (C-1); 101.6
(C-5). Mass spectrum, m/z (Irel, %): 188 [M+MeCN+H]+ (100).
Found, %: С 49.46; Н 6.80. С6Н10О4. Calculated, %:
С 49.31; Н 6.90.
(1S,4S,5R)-6,8-Dioxabicyclo[3.2.1]octan-4-ol (4).
A
round-bottom flask equipped with a magnetic stirrer,
thermometer, and bubble counter was charged with D-glu-
cose (39 g) and water (390 ml). Baker's yeast
(Saccharomyces cerevisiae) (50 g) was added to the
solution and the mixture was stirred for 1 h at 30°С. After
1 h, Cyrene (2) (5.00 g, 39.0 mmol) was added. The
mixture was stirred at the same temperature for additional
24 h. The reaction mixture was filtered, the filtrate was
evaporated, the residue was separated chromatographically
using petroleum ether – EtOAc as eluent, gradient from 2:1 to
1:1. Yield 5.02 g (99%), partially crystallizing oil, [α]D20 –134.2°
(1S,4S,5R)-4-Methyl-6,8-dioxabicyclo[3.2.1]octan-4-ol
(8). A solution of alcohol 7 (1.00 g, 7.04 mmol) in EtOAc
(10 ml) was treated by the addition of activated Raney
nickel (0.1 g). The reaction mixture was stirred under
hydrogen atmosphere. The reaction mixture was filtered
after 48 h, the filtrate was concentrated, the residue was
separated chromatographically, using petroleum ether –
EtOAc as eluent, gradient from 3:1 to 1:1. Yield 0.90 g
20
(89%), colorless oil, [α]D –77.1° (c 1.0, CHCl3). Rf 0.3
(petroleum ether – EtOAc, 2:1). IR spectrum, ν, cm–1:
34

Chemistry of Heterocyclic Compounds 2019, 55(1), 31–37
1
3443, 1131, 1085, 988, 892. H NMR spectrum, δ, ppm
(J, Hz): 1.17 (3Н, s, CH3); 1.45–1.54 (1Н, m, 2-СНexo);
1.56–1.70 (2Н, m, 3-СН2); 1.75–1.90 (1Н, m, 2-СНendo);
2.48 (1Н, br. s, OH); 3.70–3.75 (1Н, m) and 3.80 (1Н, d,
J = 6.7, 7-СН2); 4.41–4.48 (1Н, m, 1-СН); 4.93 (1Н, s,
5-СН). 13C NMR spectrum, δ, ppm: 21.8 (CH3); 27.3 (C-2);
31.9 (C-3); 67.4 (C-7); 70.5 (C-4); 73.2 (C-1); 105.9 (C-5).
Mass spectrum, m/z (Irel, %): 127 [M–H2O+H]+ (100).
Found, %: С 58.23; Н 8.46. С7Н12О3. Calculated, %:
С 58.32; Н 8.39.
Yield 0.88 g (76%, method I), 0.80 g (70%, method II);
26
colorless partially crystallizing oil, [α]D –113.5° (c 1.0,
20
CHCl3) ([α]D
–114.5° (c 0.1, CHCl3)16b). Rf 0.2
(petroleum ether – EtOAc, 1:1). IR spectrum, ν, cm–1:
3415, 2941, 1728, 1170, 1050. H NMR spectrum, δ, ppm
1
(J, Hz): 3.74 (1H, dd, J = 12.3, J = 4.9) and 3.94 (1H, dd,
J = 12.3, J = 3.8, СH2ОН); 5.10–5.16 (1H, m, 5-СH); 6.15
(1H, dd, J = 5.8, J = 1.9, 3-СH); 7.50 (1H, dd, J = 5.8,
J = 1.4, 4-СH). 13C NMR spectrum, δ, ppm: 62.0
(CН2ОН); 84.4 (C-5); 122.7 (C-3); 154.2 (C-4); 173.7
(C-2). Mass spectrum, m/z (Irel, %): 115 [M+Н]+ (100).
Found, %: C 52.73; H 5.28. C5H6O3. Calculated, %:
C 52.63; H 5.30.
Methylsulfanylmethylation of hydroxy groups in
alcohols 3, 4, 6а, 7–10 (General procedure). Method III
(methylsulfanylmethylation with DMSO and Ac2O). A
solution of alcohol 3, 4, 7, or 8 (5 mmol) in DMSO (10 ml)
and Ас2О (10 ml) was stirred for 2 h at 40°С. The reaction
mixture was quenched by adding ice and saturated
NaHCO3 solution until the evolution of gas ceased. The
aqueous phase was extracted with EtOAc, the combined
extracts were washed with NaHCO3 solution, water, dried
over anhydrous MgSO4, evaporated, the residue was
separated by chromatography on silica gel, using petroleum
ether – EtOAc as eluent, gradient from 5:1 to 2:1.
Baeyer–Villiger oxidation of levoglucosenone (1) and
Cyrene (2) (General procedure). Method I (oxidation with
5 equiv of 30% H2O2 in the presence of Amberlyst 15
resin). A mixture of ketone 1 or 2 (10.0 mmol) and
Amberlyst 15 (42 mg, 2.0 mmol, ion exchange capacity
≥4.7 equiv/kg) in water (1.5 ml) was cooled to 0°С and
treated by dropwise addition of 30% H2O2 solution (5.1 ml,
5 mmol). After the addition of H2O2 was complete, the
reaction mixture was heated to 50°С and stirred for 1 h, then
cooled to room temperature and quenched with saturated
Na2SO3 solution until complete removal of peroxides
(determined with 10% KI solution). Water was then
removed by distillation at reduced pressure, the precipitate
was filtered off and washed with EtOH. The filtrate was
evaporated on a rotary evaporator, the residue was
separated by chromatography on silica gel, using petroleum
ether – EtOAc as eluent, gradient from 2:1 to 1:1.
Method IV (methylsulfanylmethylation with DMSO,
Ac2O, and AcOH). A solution of alcohol 3 or 4 (1.0 mmol)
in a mixture of DMSO (1.5 ml), Ас2О (1.0 ml), and AcOH
(0.4 ml) was stirred for 2 h at 40°С. The reaction mixture
was quenched by adding ice and saturated NaHCO3
solution until the evolution of gas ceased. The aqueous
phase was extracted with EtOAc, the combined extracts
were washed with NaHCO3 solution, water, dried over
anhydrous MgSO4, evaporated, and the residue was
separated by chromatography on silica gel, using petroleum
ether – EtOAc as eluent, gradient from 5:1 to 2:1.
Method II (oxidation with 1 equiv of 30% H2O2 and
Amberlyst 15). A mixture of ketone 1 or 2 (10.0 mmol) and
Amberlyst 15 (42 mg, 2.0 mmol, ion exchange capacity
≥4.7 equiv/kg) in water (1.5 ml) was cooled to 0°С and
treated by dropwise addition of 30% H2O2 solution
(1.02 ml, 1 mmol). After the addition of H2O2 was
complete, the reaction mixture was heated to 50°С and
stirred for 2 h. The reaction mixture was then cooled to
room temperature. The residual peroxides, if present, were
neutralized with Na2SO3. Amberlyst 15 resin was removed
from the reaction mixture by filtration, washed with water,
the filtrate was concentrated at reduced pressure, the
residue was separated by chromatography on silica gel,
using petroleum ether – EtOAc as eluent, gradient from 2:1
to 1:1 (or distilled at reduced pressure of 0.7–0.9 mbar).
(S)-5-(Hydroxymethyl)dihydrofuran-2(3H)-one (9)
was obtained from Cyrene (2) (1.28 g, 10.0 mmol)
according to method I or II. Yield 1.01 g (87%, method I),
Method
V (methylsulfanylmethylation with Me2S,
(PhCO2)2, MeCN). A solution of alcohol 3, 4, 6а, 9, or 10
(1.0 mmol) in anhydrous acetonitrile (4.0 ml) was cooled to
0°С and treated by adding Me2S (0.58 ml, 8 mmol). After
that, benzoyl peroxide (986 mg, 4 mmol) was added in
4 portions over 30 min intervals. The mixture was stirred for
2 h at 0°С, diluted with Et2O, and then washed with
saturated NaHCO3 solution. The aqueous phase was
extracted with Et2O, dried over anhydrous MgSO4,
evaporated, the residue was separated by chromatography
on silica gel, using petroleum ether – EtOAc as eluent,
gradient from 5:1 to 2:1.
0.97 g (84%, method II), colorless oil, [α]D26 +57.0° (c 1.0,
20
CHCl3) ([α]D
+52.9° (c 0.01, CHCl3)16с). Rf 0.2
(petroleum ether – EtOAc, 1:1). IR spectrum, ν, cm–1:
1
3409, 1761, 1188, 1062, 936, 653. H NMR spectrum, δ,
(1S,4S,5R)-4-Methyl-4-[(methylsulfanyl)methoxy]-6,8-di-
oxabicyclo[3.2.1]oct-2-ene (11) was obtained from alcohol
7 (710 mg, 5.0 mmol) according to method III. Yield
999 mg (99%). The spectral characteristics of ether 11 were
identical to those described in the literature.14
ppm (J, Hz): 2.09 (1H, dddd, J = 18.1, J = 10.0, J = 8.0,
J = 7.2) and 2.22 (1H, dddd, J = 18.1, J = 9.8, J = 7.6,
J = 5.9, 4-СН2); 2.47 (1H, ddd, J = 17.9, J = 9.8, J = 8.0)
and 2.56 (1H, ddd, J = 17.9, J = 10.0, J = 5.9, 3-СН2); 3.58
(1Н, br. s, OH); 3.58 (1H, dd, J = 12.5, J = 4.6) and 3.82
(1H, dd, J = 12.5, J = 3.7, СH2ОН); 4.55–4.60 (1H, m,
5-СH). 13C NMR spectrum, δ, ppm: 23.1 (C-4); 28.7 (C-3);
63.9 (CН2ОН); 81.0 (C-5); 178.2 (C-2). Mass spectrum, m/z
(Irel, %): 158 [M+MeCN+Н]+ (100). Found, %: C 51.62;
H 6.99. C5H8O3. Calculated, %: C 51.72; H 6.94.
(1S,4S,5R)-4-Methyl-4-[(methylsulfanyl)methoxy]-6,8-di-
oxabicyclo[3.2.1]octane (12) was obtained from alcohol 8
(720 mg, 5.0 mmol) according to method III. Yield 928 mg
20
(91%), colorless oil, [α]D –45.8° (c 1.0, CHCl3). Rf 0.35
(petroleum ether – EtOAc, 3:1). IR spectrum, ν, cm–1: 1484,
1
1095, 1045, 987, 931. H NMR spectrum, δ, ppm (J, Hz):
(S)-5-(Hydroxymethyl)furan-2(5H)-one (10) was
obtained from levoglucosenone (1) (1.26 g, 10.0 mmol).
1.30 (3Н, s, СН3); 1.51–1.56 (1Н, m) and 1.65–1.69 (1Н,
m, 2-СН2); 1.83–1.91 (1Н, m) and 1.93 (1Н, dd, J = 12.7,
35

Chemistry of Heterocyclic Compounds 2019, 55(1), 31–37
J = 5.4, 3-СН2); 2.18 (3Н, s, СН3); 3.76 (1Н, dd, J = 7.1,
Rf 0.3 (CH2Cl2). IR spectrum, ν, cm–1: 1216, 1074, 967,
757. 1H NMR spectrum, δ, ppm (J, Hz): 2.08 (3Н, s, СН3);
3.67 (1Н, m) and 3.85 (1Н, d, J = 6.6, 7-СН2); 4.44 (1Н, s,
4-CН); 4.53–4.57 (1Н, m, 1-CН); 4.62 (1Н, d, J = 11.8)
and 4.69 (1Н, d, J = 11.8, СН2S); 5.54 (1Н, d, J = 1.5,
5-CН); 5.60 (1Н, dd, J = 9.9, J = 1.5, 3-CН); 6.03 (1Н, dd,
J = 9.9, J = 4.1, 2-CН). 13C NMR spectrum, δ, ppm: 13.5
(CH3); 71.3 (C-7); 71.4 (C-4); 73.9 (C-1); 74.0 (CH2S); 100.2
(C-5); 126.0 (C-2); 131.2 (C-3). Mass spectrum, m/z (Irel, %):
189 [M+Н]+ (100). Found, %: C 51.12; H 6.47; S 16.93.
C8H12O3S. Calculated, %: C 51.04; H 6.43; S 17.03.
J = 4.8) and 3.85 (1Н, d, J = 7.1, 7-СН2); 4.43–4.49 (1Н,
m, 1-СН); 4.61 (1Н, d, J = 11.1) and 4.64 (1Н, d, J = 11.1,
СН2S); 5.17 (1Н, s, 5-СН). 13C NMR spectrum, δ, ppm: 14.2
(CH3); 19.5 (CH3); 27.2 (C-2); 28.3 (C-3); 67.3 (CH2S);
67.7 (C-7); 73.4 (C-1); 76.7 (C-4); 104.2 (C-5). Mass
spectrum, m/z (Irel, %): 205 [M+Н]+ (100). Found, %:
C 52.99; H 7.73; S 15.56. C9H16O3S. Calculated, %:
C 52.91; H 7.89; S 15.70.
(1S,4S,5R)-4-[(Methylsulfanyl)methoxy]-6,8-dioxabicyclo-
[3.2.1]octane (13) and [((1S,4S,5R)-6,8-dioxabicyclo-
[3.2.1]octan-4-yloxy)methyl]acetate (14) were obtained as a
mixture containing also Cyrene (2), starting from alcohol 4
(650 mg, 5.0 mmol, method III or 130 mg, 1.0 mmol,
methods IV, V).
[((1S,4S,5R)-6,8-Dioxabicyclo[3.2.1]oct-2-en-4-yloxy)-
methyl]acetate (16). Yield 10 mg (5%), colorless oil,
[α]D20 –11.2° (c 1.0, CHCl3). Rf 0.2 (CH2Cl2). IR spectrum,
1
ν, cm–1: 1730, 1226, 1117, 975, 831. H NMR spectrum,
(1S,4S,5R)-4-[(Methylsulfanyl)methoxy]-6,8-dioxabicyclo-
[3.2.1]octane (13). Yield 580 mg (61%, method III), 127 mg
(67%, method IV), 141 mg (74%, method V), colorless oil,
δ, ppm (J, Hz): 2.07 (3Н, s, СН3); 3.75 (1Н, dd, J = 6.6,
J = 4.2) and 3.93 (1Н, d, J = 6.6, 7-СН2); 4.44 (1Н, br. s,
4-CН); 4.63 (1Н, t, J = 4.2, 1-CН); 5.27 (1Н, d, J = 6.4)
and 5.45 (1Н, d, J = 6.4, OСН2О); 5.57 (1Н, t, J = 2.1,
5-CН); 5.65 (1Н, dt, J = 9.9, J = 2.1, 3-CН); 6.13 (1Н, ddd,
J = 9.9, J = 4.1, J = 1.0, 2-CН). 13C NMR spectrum,
δ, ppm: 21.7 (CH3); 71.9 (C-4); 72.0 (C-7); 78.0 (C-1);
89.1 (OCH2О); 101.0 (C-5); 126.4 (C-2); 132.3 (C-3);
170.9 (СО). Mass spectrum, m/z (Irel, %): 218
[M–OAc+2Н2O+MeCN]+ (100). Found, %: C 54.08;
H 5.95. C9H12O5. Calculated, %: C 54.00; H 6.04.
20
[α]D –73.0° (c 1.0, CHCl3). Rf 0.3 (petroleum ether –
EtOAc, 3:1). IR spectrum, ν, cm–1: 1437, 1134, 1072, 970,
1
902, 680. H NMR spectrum, δ, ppm (J, Hz): 1.57 (1Н, dd,
J = 13.0, J = 6.1, 2-СНexo); 1.65 (1Н, ddd, J = 12.6, J = 10.5,
J = 6.1, 3-СНendo); 1.82–1.88 (1Н, m, 2-СНendo); 1.90–1.95
(1Н, m, 3-СНexo); 2.10 (3Н, s, СН3); 3.67 (1Н, dd, J = 9.3,
J 6.1, 4-СН); 3.76 (1Н, dd, J = 7.2, J = 6.0) and 3.84 (1Н, d,
J = 7.2, 7-СН2); 4.59–4.64 (1Н, m, 1-СН); 4.60 (1Н, d,
J = 11.7) and 4.64 (1Н, d, J = 11.7, СН2S); 5.37 (1Н, s,
5-СН). 13C NMR spectrum, δ, ppm: 13.5 (CH3); 22.5
(C-3); 27.8 (C-2); 68.3 (C-7); 73.0 (C-1); 73.1 (CH2S); 73.5
(C-4); 101.2 (C-5). Mass spectrum, m/z (Irel, %): 191 [M+Н]+
(100). Found, %: C 50.60; H 7.49; S 16.76. C8H14O3S.
Calculated, %: C 50.50; H 7.42; S 16.85.
Levoglucosenone (1). Yield 40 mg (32%).
Methylthiomethylation of alcohol (5) (144 mg,
1.0 mmol) according to method IV gave levoglucosenone
(1). Yield 96 mg (76%).
(1R,2S,4S,5R)-2,4-Bis[(methylsulfanyl)methoxy]-6,8-di-
oxabicyclo[3.2.1]octane (17) was obtained from alcohol 6а
(146 mg, 1.0 mmol) according to method V. Yield 168 mg
[((1S,4S,5R)-6,8-Dioxabicyclo[3.2.1]octan-4-yloxy)methyl]-
acetate (14). Yield 232 mg (23%, method III), 28 mg
20
(63%), colorless oil, [α]D –26.0° (c 1.0, CHCl3). Rf 0.4
20
(14%, method IV), colorless oil, [α]D –81.3° (c 1.0,
(petroleum ether – EtOAc, 3:1). IR spectrum, ν, cm–1: 1074,
1036, 975, 903. 1H NMR spectrum, δ, ppm (J, Hz): 1.71 (1Н,
ddd, J = 14.5, J = 10.5, J = 4.4) and 2.11–2.15 (1Н, m,
3-СН2); 2.11 (3H, s, CH3); 2.15 (3H, s, CH3); 3.77 (1Н, d,
J = 7.2) and 3.80 (1Н, dd, J = 7.2, J = 5.2, 7-СН2); 3.83–
3.87 (1Н, m, 2-CН); 3.87 (1Н, dd, J = 10.5, J = 5.0, 4-CН);
4.50–4.54 (1Н, m, 1-CН); 4.61 (1H, d, J = 11.8), 4.65 (1H,
d, J = 11.8), 4.66 (1H, d, J = 11.8) and 4.74 (1H, d,
J = 11.8, 2CH2S); 5.46 (1Н, s, 5-CН). 13C NMR spectrum,
δ, ppm: 13.6 (CH3); 13.7 (CH3); 27.7 (C-3); 66.5 (C-7);
71.5 (C-4); 71.9 (C-2); 72.6 (CH2S); 73.6 (CH2S); 74.7
(C-1); 101.0 (C-5). Mass spectrum, m/z (Irel, %): 267
[M+H]+ (100). Found, %: С 45.01; Н 6.83, S 23.98.
С10Н18О4S2. Calculated, %: С 45.09; Н 6.81; S 24.07.
CHCl3). Rf 0.3 (petroleum ether – EtOAc, 2:1). IR spect-
1
rum, ν, cm–1: 1739, 1216, 1122, 1013, 943, 756. H NMR
spectrum, δ, ppm (J, Hz): 1.61 (1Н, dd, J = 13.6, J = 5.9,
2-СНexo); 1.71 (1Н, ddd, J = 12.8, J = 10.4, J = 5.9,
3-СНendo); 1.84–1.89 (1Н, m, 2-СНendo); 1.94–2.00 (1Н, m,
3-СНexo); 2.07 (3Н, s, СН3); 3.62 (1Н, dd, J = 10.1, J = 6.0,
4-СН); 3.79 (1Н, dd, J = 7.1, J = 6.0) and 3.87 (1Н, d,
J = 7.1, 7-СН2); 4.44–4.49 (1Н, m, 1-СН); 5.24 (1Н, d,
J = 6.4) and 5.34 (1Н, d, J = 6.4, ОСН2O); 5.39 (1Н, s,
5-СН). 13C NMR spectrum, δ, ppm: 21.1 (CH3); 22.7
(C-3); 27.7 (C-2); 68.3 (C-7); 72.9 (C-1); 77.0 (C-4); 87.9
(ОCH2O); 101.2 (C-5); 170.3 (C=O). Mass spectrum, m/z
(Irel, %): 220 [M–OAc+2Н2O+MeCN]+ (100). Found, %:
C 53.49; H 7.07. C9H14O5. Calculated, %: C 53.46; H 6.98.
(1S,4S,5R)-6,8-Dioxabicyclo[3.2.1]octan-4-ol (2). Yield
32 mg (5%, method III), 6 mg (5%, method IV).
(S)-5-[(Methylsulfanyl)methoxy]dihydrofuran-2(3H)-
one (18) was obtained from lactone 9 (116 mg, 1.0 mmol)
according to method V. Yield 146 mg (83%), colorless oil,
20
(1S,4S,5R)-4-[(Methylsulfanyl)methoxy]-6,8-dioxabicyclo-
[3.2.1]oct-2-ene (15) and [((1S,4S,5R)-6,8-dioxabicyclo-
[3.2.1]oct-2-en-4-yloxy)methyl]acetate (16) were obtained
as a mixture containing also levoglucosenone (1), starting
from alcohol 3 (128 mg, 1.0 mmol) according to method IV.
Ether 15 was also obtained from alcohol 3 (128 mg,
1.0 mmol) according to method V.
(1S,4S,5R)-4-[(Methylsulfanyl)methoxy]-6,8-dioxabicyclo-
[3.2.1]oct-2-ene (15). Yield 68 mg (36%, method IV), 133 mg
(71%, method V), colorless oil, [α]D20 +9.1° (c 1.0, CHCl3).
[α]D +27.3° (c 1.0, CHCl3). Rf 0.3 (petroleum ether –
EtOAc, 3:1). IR spectrum, ν, cm–1: 2925, 1769, 1216, 1109,
1
948, 757. H NMR spectrum, δ, ppm (J, Hz): 2.06 (3H, s,
CH3); 2.03–2.09 (1H, m) and 2.22–2.28 (1H, m, 4-СH2);
2.45 (1H, ddd, J = 17.3, J = 9.9, J = 7.3) and 2.51 (1H, ddd,
J = 17.3, J = 10.0, J = 6.4, 3-СН2); 3.58 (1H, dd, J = 10.8,
J = 4.4) and 3.70 (1H, dd, J = 10.8, J = 3.0, СH2О); 4.58
(1Н, d, J = 11.7) and 4.61 (1Н, d, J = 11.7, СН2S); 4.61–
4.64 (1H, m, 5-СH). 13C NMR spectrum, δ, ppm: 13.8 (СН3);
24.0 (C-4); 28.4 (C-3); 69.1 (CН2О); 75.6 (СН2S); 78.6
36

Chemistry of Heterocyclic Compounds 2019, 55(1), 31–37
(C-5); 177.3 (C-2). Mass spectrum, m/z (Irel, %): 177 [M+Н]+
(100). Found, %: C 47.73; H 6.95; S 18.16. C7H12O3S.
Calculated, %: C 47.71; H 6.86; S 18.19.
3. (a) Kuno, H.; Niihata, S.; Ebata, T.; Matsushita, H.
Heterocycles 1995, 41, 523. (b) Jung, M. E.; Kiankarimi, M.
J. Org. Chem. 1998, 63, 8133.
4. Ebata, T.; Matsumoto, K.; Yoshikoshi, H.; Koseki, K.;
Kawakami, H.; Matsushita, H. Heterocycles 1990, 31, 1585.
5. (a) Valeev, F. A.; Gorobets, E. V.; Tsypysheva, I. P.;
Singizova, G. Sh.; Kalimullina, L. Kh.; Safarov, M. G.;
Shitikova, O. V.; Miftakhov, M. S. Chem. Nat. Compd. 2003,
39, 563. [Khim. Prirod. Soedin. 2003, 39, 465.] (b) Mori, M.;
Chuman, T.; Kato, K.; Mori, K. Tetrahedron Lett. 1982, 23,
4593. (c) Witczak, Z. J.; Li, Y. Tetrahedron Lett. 1995, 36, 2595.
6. Tolstikov, G. A.; Valeev, F. A.; Gaisina, I. N.; Spirikhin, L. V.;
Miftakhov, M. S. J. Org. Chem. USSR 1992, 28, 1659. [Zh.
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7. (a) Witczak, Z. J.; Kaplon, P.; Dey, P. M. Carbohydr. Res.
2003, 338, 11. (b) Czubatka-Bieńkowska, A.; Sarnik, J.;
Macieja, A.; Galita, G.; Witczak, Z. J.; Poplawski, T. Bioorg.
Med. Chem. Lett. 2017, 27, 2713. (c) Giri, G. F.; Danielli, M.;
Marinelli, R. A.; Spanevello, R. A. Bioorg. Med. Chem. Lett.
2016, 26, 3955.
8. Giri, G. F.; Viarengo, G.; Furlán, R. L. E.; Suárez, A. G.;
Garcia Véscovi, E.; Spanevello, R. A. Ind. Crops Prod. 2017,
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30, 59.
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US Patent US20120111714. (b) Alves Costa Pacheco, A.;
Sherwood, J.; Zhenova, A.; McElroy, C. R.; Hunt, A. J.;
Parker, H. L.; Farmer, T. J.; Constantinou, A.; De bruyn, M.;
Whitwood, A. C.; Raverty, W.; Clark, J. H. ChemSusChem
2016. 9. 3503.
11. (a) Sherwood, J.; De bruyn, M.; Constantinou, A.; Moity, L.;
McElroy, C. R.; Farmer, T. J.; Duncan, T.; Raverty, W.;
Hunta A. J.; Clark, J. H. Chem. Commun. 2014, 50, 9650.
(b) Shafizadeh, F.; Chin, P. S. Carbohydr. Res. 1977, 58, 79.
12. Shafizadeh, F.; Furneaux, R. H.; Stevenson, T. T. Carbohydr.
Res. 1979, 71,169.
(S)-5-[(Methylsulfanyl)methoxy]furan-2(5H)-one (19)
was obtained from lactone 10 (114 mg, 1.0 mmol)
according to method V. Yield 139 mg (80%), colorless oil,
20
[α]D –112.4° (c 1.0, CHCl3). Rf 0.2 (petroleum ether –
EtOAc, 3:1). IR spectrum, ν, cm–1: 2922, 1785, 1741, 1164,
1
1086, 957, 820. H NMR spectrum, δ, ppm (J, Hz): 2.07
(3H, s, CH3); 3.73 (1H, dd, J = 10.6, J = 5.2) and 3.78 (1H,
dd, J = 10.6, J = 4.4, СH2О); 4.61 (2Н, s, СН2S); 5.14–5.20
(1H, m, 5-СH); 6.12 (1H, dd, J = 5.8, J = 2.0, 3-СH); 7.46
(1H, dd, J = 5.8, J = 1.4, 4-СH). 13C NMR spectrum,
δ, ppm: 13.8 (СН3); 66.8 (CН2О); 75.7 (СН2S); 81.9 (C-5);
122.7 (C-3); 153.6 (C-4); 172.8 (C-2). Mass spectrum, m/z
(Irel, %): 192 [M–Me+MeOH+H]+ (100). Found, %:
C 48.36; H 5.80; S 18.36. C7H10O3S. Calculated, %:
C 48.26; H 5.79; S 18.41.
Evaluation of fungicidal activity was performed by
agar diffusion method.25 The surface of growth medium
(potato glucose agar) that was poured in 15 ml portions on
70 mm Petri dishes was inoculated with fungal test culture
spore suspension at the density of 104 CFU/ml. A 10 mm
drill bit was then used to drill wells into the growth
medium that were inoculated with solutions (100 µl) of the
study compounds. The fungicidal activity was determined
from the diameter of zone where the growth of
micromycetes was suppressed, as well as by observing the
development of test cultures using a Leica Microsystems
DM1000 optical microscope at 10× magnification. The
experiments were repeated in triplicate. Fungal
development on growth medium was used as control. The
incubation time was 7 days at 28°С. The test cultures were
Bipolaris sorokiniana, Fusarium oxysporum, and
Rhizoctonia solani.
13. (a) Fantin, G.; Fogagnolo, M.; Guerzoni, M. E.; Medici, A.;
Pedrini, P.; Poli, S. J. Org. Chem. 1994, 59, 924. (b) Inoue, T.;
Hosomi, K.; Araki, M.; Nishide, K.; Node, M. Tetrahedron:
Asymmetry 1995, 6, 31.
A Supplementary information file containing NMR
spectra of all synthesized compounds is available at the
journal website at http://link.springer.com/journal/10593
14. Davydova, A. N.; Sharipov, B. T.; Valeev, F. A. Russ. J. Org.
Chem. 2015, 51, 1408. [Zh. Org. Khim. 2015, 51, 1440.]
15. Tsypysheva, I. P.; Valeev, F. A.; Vasil'eva, E. V.;
Spirikhin, L. V.; Tolstikov, G. A. Russ. Chem. Bull., Int. Ed.
2000, 49, 1237. [Izv. Akad. Nauk, Ser. Khim. 2000, 1240.]
16. (a) Koseki, K.; Ebata, T.; Kawakami, H.; Matsushita, H.;
Naoi, Y.; Itoh, K. Heterocycles 1990, 31, 423. (b) Paris, C.;
Moliner, M.; Corma, A. Green Chem. 2013, 15, 2101.
(c) Flourat, A. L.; Peru, A. A. M.; Teixeira, A. R. S.;
Brunissena, F.; Allais, F. Green Chem. 2015, 17, 404.
17. Davydova, A. N.; Pershin, A. A.; Sharipov, B. T.; Valeev, F. A.
Mendeleev Commun. 2015, 25, 271.
The work was performed according to the State contracts
No. АААА-А17-117011910022-5, АААА-А18-118022190098-9)
and with financial support from the Russian Foundation for
Basic Research (grant 17-43-020166 r_a).
Analytical support was provided using equipment at the
Collective Use Center “Chemistry” of the Institute of
Chemistry, Ufa Federal Research Center of the Russian
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