Synthesis and oxidation of thioglicosides underlain by neomenthanethiol, D-glucose, and D-fructose

Article abstract of DOI:10.1134/S1070428014050091

Synthesis of sulfides proceeding from neomenthanethiol, 1,2-O-isopropylidene-α-D-glucofuranose and 2,3:4,5-di-O-isopropylidene- β-D-fructopyranose was performed to get 65 and 54% yield respectively. Oxidation of the sulfides afforded diastereomeric sulfoxides in the yields from 40 to 53%, and diastereomeric excess (de) up to 36%. After removing the isopropylidene protection from 1-deoxy-1-[(1S,2S,5R)-2-isopropyl-5- methylcyclohexylsulfanyl]-2,3:4,5-di-O-isopropylidene-β-D-fructopyranose a water-soluble sulfide was obtained.

Full text of DOI:10.1134/S1070428014050091

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2014, Vol. 50, No. 5, pp. 670–677. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © S.V. Pestova, E.S. Izmest’ev, S.A. Rubtsova, A.V. Kuchin, 2014, published in Zhurnal Organicheskoi Khimii, 2014, Vol. 50, No. 5,
pp. 684–690.
Synthesis and Oxidation of Thioglicosides Underlain
by Neomenthanethiol, D-Glucose, and D-Fructose
S. V. Pestova, E. S. Izmest’ev, S. A. Rubtsova, and A. V. Kuchin
Institute of Chemistry, Komi Scientific Center, Ural Branch, Russian Academy of Sciences,
Pervomaiskaya ul. 48, Syktyvkar, 167982 Russia
e-mail: pestova-sv@chemi.komisc.ru
Received October 25, 2013
Abstract—Synthesis of sulfides proceeding from neomenthanethiol, 1,2-О-isopropylidene-α-D-glucofuranose
and 2,3:4,5-di-O-isopropylidene-β-D-fructopyranose was performed to get 65 and 54% yield respectively.
Oxidation of the sulfides afforded diastereomeric sulfoxides in the yields from 40 to 53%, and diastereomeric
excess (de) up to 36%. After removing the isopropylidene protection from 1-deoxy-1-[(1S,2S,5R)-2-isopropyl-
5-methylcyclohexylsulfanyl]-2,3:4,5-di-O-isopropylidene-β-D-fructopyranose a water-soluble sulfide was
obtained.
DOI: 10.1134/S1070428014050091
Carbohydrates owing to their special structure are
the main energy source for cells of living bodies. The
change in the structure of naturally occurring
monosaccharides by replacing one or several hydroxy
groups with other functional groups results in
enhancement or in removal of their biologic activity.
The replacement of one or several oxygen fragments of
a monosaccharide with sulfur-containing groups is an
important task for the medicinal chemistry since the
synthetic thioglicosides possess a wide range of
biologic action, e.g., the ability to inhibit insulin
production [1], to exhibit antithrombotic [2, 3], anti-
cancer, and antiviral action [4, 5].
galactose. The removal of the isopropylidene protect-
tion from the galactose fragment of sulfides and
sulfoxides led to the formation of water-soluble
compounds [6]. In this research a synthesis was carried
out of new sulfides, 6-deoxy-6-[(1S,2S,5R)-2-iso-
propyl-5-methylcyclohexylsulfanyl]-1,2-O-isopro-
pylidene-α-D-glucofuranose (I) and 1-deoxy-1-
[(1S,2S,5R)-2-isopropyl-5-methylcyclohexylsulfanyl]-
2,3:4,5-di-O-isopropylidene-β-D-fructopyranose (II)
proceeding from naturally occurring D-glucose (III)
and D-fructose (IV) through the intermediate forma-
tion of their diacetone derivatives V and VI (Scheme 1).
Due to thermodynamic reasons the formation of
glucose diacetonide (V) is accompanied with the
contruction of the initial pyranose ring of the
monosaccharide into the furanose one whereas the
fructose, in contrast, at introducing the diacetonide
protection forms fructopyranose diacetonide (VI)
[7, 8]. The yields of diisopropylidene derivatives V
and VI reached 77 and 90% respectively.
In most cases the naturally occurring mono-
saccharides are well soluble in water environment. The
introduction into the monosaccharide structure of a
biologically active lipophilic fragment, for instance,
terpene moiety, makes it possible to bring the latter
into the aqueous solution on occasion of the retention
of the water-solubility of the formed conjugate. No
less importance has the retention of the diastereomeric
purity (de) of new compounds since the mono-
saccharides are known to be capable to form easily
epimeric compounds possessing different kinds of
activity.
The hydroxy group at the atom С3 in compound V
due to the spatial hindrance does not enter in the
nucleophilic substitution SN2 and is not worth for the
selective preparation of sulfides. However the action of
equimolar quantity of hydrochloric acid led to the
selective formation in 95% yield of 1,2-O-
isopropylidene-α-D-glucofuranose (VII), which was
We formerly performed a synthesis of sulfides and
sulfoxides proceeding from neomenthanethiol and D-
670

SYNTHESIS AND OXIDATION OF THIOGLICOSIDES
671
Scheme 1.
O
HO
HO
OH
H
H
O
O
O
O
(CH3)2CO
HO
HCl
OH
HO
HO
HO
H
CuSO4, H2SO4
H2O
OH
O
O
H
H
O
O
III
V
VII
10'
8'
3'
SH
9'
Ms
1'
5'
А
S
7'
O
HO
HO
Cs2CO3, t-Bu4NI
MsCl
HO
6
5
C2H5OH
Py
O
O
O
1
HO
3
O
8
VIII
O
9
I
10
9
7
H
HO
H
OH
O
5
O
O
O
H
(CH3)2CO
O
Ph3P, I2
BzIm, PhMe
H
OH
H
O
O
O
O
I
CuSO4, H2SO4
OH
H
H
3
H
H
12
1
HO
8
O
O
OH
11
IV
VI
IX
10
9
7
H
H
5
O
O
H
HO
O
O
O
HO
H
OH
H
3
12
TFA
A, Cs2CO3
H
8
1
O
OH
CHCl3
9'
8'
S
t-Bu4NI, DMF
S
11
1'
10'
5'
3'
7'
II
X
Ms is methanesulfonate, BzIm is benzimidazole, Py is pyridine.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 5 2014

PESTOVA et al.
672
Scheme 2.
O
O
S(R)
S(S)
[O]
HO
HO
I
+
O
O
HO
HO
O
O
O
O
XIa
XIb
H
H
O
O
O
H
O
H
O
O
O
O
H
H
+
[O]
O
O
O
O
II
(R)S
(S)S
XIIb
XIIa
converted into a reactive mesylate VIII in order to
obtain sulfide I. We failed to prepare the corres-
ponding mesylate from fructose diacetonide (VI)
containing a free primary ОН group at the atom С1,
therefore the synthesis of sulfide II was carried out via
iodide IX. The preparative yields of sulfides I and II
with accounting for the losses in all stages of the
synthesis attained 65 and 54% respectively.
The structure of sulfides I and II was proved by
NMR and IR spectra, the composition was confirmed
by elemental analyses. 1Н and 13С NMR spectra
contained the signals of neomenthyl and mono-
isopropylidene-substituted glucofuranose fragments in
sulfide I and of diisopropylidene-substituted fructo-
1
pyranose moiety in sulfide II. In the H NMR spec-
trum of sulfide I two characteristic doublet signals
Results of oxidation of sulfides I and II
Oxidation of sulfide I
Oxidation of sulfide II
Oxidant
prevailing
sulfoxide
prevailing
sulfoxide
yield, %
de, %
yield, %
d.e., %
m-Chloroperoxybenzoic acid
53
44
20
19
45
41
36
12
(R)-XI
(R)-XI
(R)-XII
(S)-XII
tert-Butyl hydroperoxide–
VO(acac)2
Cumyl hydroperoxide–
VO(acac)2
40
13
50
0
–
(S)-XI
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 50 No. 5 2014

SYNTHESIS AND OXIDATION OF THIOGLICOSIDES
673
appear at 4.57 and 6.00 ppm, J 3.6 Hz, belonging to
the contiguous protons H1 and H2 respectively. As
compared to glucose monoacetonide (VII) the spec-
trum of sulfide I contains only two signals of ОН
groups at 3.17 and 3.37 ppm. All signals of protons
H1–H5 in the 1H NMR spectra are observed as strongly
narrowed doublets or unresolved multiplets
(pseudosinglets) indicating the retention of the
furanose ring in the sulfide and the absence of the
axial-equatorial (а-е) location of protons that is
characteristic of the pyranose form of monosaccharides
Sulfides I and II were oxidized to sulfoxides XI
and XII with m-chloroperoxybenzoic acid, and also
with systems tert-butyl hydroperoxide–vanadyl acetyl-
acetonate[VO(acac)2] and cumyl hydroperoxide–
VO(acac)2 (Scheme 2).
Sulfoxides XI and XII were isolated by column
chromatography on silica gel and characterized by
NMR and IR spectra, the composition was confirmed
by elemental analyses. In the IR spectra of sulfoxides XI
and XII the characteristic absorption bands of the S=O
group appear in the region 1056–1076 cm–1. The 1Н and
13С NMR spectra contain signals of both neomenthyl
and protected glucofuranose and fructopyranose
1
[9]. Unlike the spectrum of sulfide I in the H NMR
spectrum of sulfide II the majority of signals of
protons H1–H6 have large spin-spin coupling constants
(up to 13.3 Hz), due apparently to the diminished
torsion angles between the protons caused by the
additional strain in the pyranose ring with
isopropylidene groups. One of protons Н6 and the
proton H5 probably form a pseudoaxial angle resulting
in the increase in J(Н5) to 8 and J(Н6а) to 13 Hz.
1
fragments. In the H NMR spectra of compounds XIа
and XIb the doublet signals of the protons H1 and Н2,
J 3.6 Hz, were conserved showing that the
carbohydrate moiety remained in the furanose form. In
sulfoxides XIIа and XIIb the torsion angles between
protons and the corresponding coupling constants
(J 13.5 Hz) were retained like in the initial sulfide II.
The structures of sulfides I and II are confirmed by
characteristic NOE interactions. In the NOESY
spectrum of sulfide I cross-peaks were observed
between the protons H1 and H2, proving the α-form of
the anomeric center C1, and on the contrary, NOE
interaction of the protons H1 and H3 of sulfide II
showed the β-form of the anomeric center C2.
All characteristic NOE interactions in the spectra of
sulfoxides XI and XII remain the same as in initial
sulfides I and II both in the neomenthyl and protected
glucofuranose and fructopyranose fragments.
It was formerly discovered in [6, 10] that the
change in the configuration of the S-chiral center of the
sulfinyl group bound to the neomenthyl fragment
resulted in a significant change in the chemical shift of
In the IR spectra of sulfides I and II absorption
bands are present characteristic of the stretching
vibrations of the О–С–О group in the region 1166 cm–1
and of ОН group at 3439 cm–1 in sulfide I.
13
the atom С6' in the С NMR spectrum that provided a
possibility to predict with a high probability the
configuration of the S=O group. Sulfoxides XIb and
XIIb having the signals of the С6' atoms in the stronger
field (34.12 and 34.60 ppm) compared to atoms
C4' (34.95 and 35.35 ppm) possess the (S)-configure-
tion of the sulfinyl group, and sulfoxides XIа and XIIa
whose signals of С6' atoms are located downfield
(38.75 and 36.99 ppm) from the signals of С4' (35.42
and 35.59 ppm), have the (R)-configuration (see the
table).
We succeeded to remove the protecting
isopropylidene groups in sulfide II and obtained as a
result water-soluble 1-deoxy-1-[(1S,2S,5R)-2-iso-
propyl-5-methylcyclohexylsulfanyl]-β-D-fructopyranose
(X) in a 62% yield. In the 1H NMR spectrum of sulfide
X the signals were observed of the neomenthyl
fragment, and the signals of the isopropylidene methyl
1
groups were absent. The set of signals in the H and
13С NMR spectra proved that sulfide X formed in the
more stable β-form virtually incapable to convert into
α-form due to arising additional steric hindrances
caused by the neomenthyl fragment. The IR spectrum
of sulfide X contains new strong bands of the
stretching vibrations of ОН groups at 3385 cm–1. The
removal of the isopropylidene protection in sulfide I
with CF3COOH at room temperature was unsuc-
cessful, the heating of the reaction mixture at 50°С led
to complete tarring.
Oxidation of sulfides I and II with three oxidants
occurred with moderate yields of sulfoxides from 40 to
53%. We used an equivalent amount of the oxidant
that did not lead to complete conversion of the sulfide.
At excess of oxidant the reaction mixture suffered a
strong tarring and the yield of sulfoxides reduced to
20%. The change of the oxidant weakly affects the
diastereoselectivity of the oxidation. For instance, at
the oxidation of sulfide I the de value of the obtained
sulfoxides was in the range 13–20%.
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PESTOVA et al.
674
We succeeded to attain the highest diastere-
1,2-O-Isopropylidene-α-D-glucofuranos-6-yl-
mеthanesulfonate (VIII) was obtained by procedure
[16] and was used unpurified after distilling off the
solvent.
oselectivity at the oxidation of sulfide II with m-
chloroperoxybenzoic acid (de 36%). In most cases the
prevailing sulfoxide has the (R)-configuration of the
sulfinyl group (see the table). We failed to remove the
isopropylidene protection in the obtained sulfoxides.
The treatment with trifluoroacetic acid in CHCl3 led to
the complete tarring of the reaction mixture.
1-Deoxy-1-iodo-2,3:4,5-di-O-isopropylidene-β-D-
fructopyranose (IX) was obtained by procedure [15].
Yield 64%, [α]D22 –47.6 (с 0.88, СНCl3).
6-Deoxy-6-[(1S,2S,5R)-2-isopropyl-5-methylcyc-
lohexylsulfanyl]-1,2-O-isopropylidene-α-D-glucofu-
ranose (I). In 3 mL of EtOH was dissolved at stirring
under argon 1.3 mmol (0.246 g) of neomenthanethiol
(III), 1.3 mmol (0.421 g) of cesium carbonate, and
1.3 mmol (0.478 g) of t-Bu4NI. After 5 min 1 mmol
(0.32 g) of mesylate VIII was added to the above
mixture. The reaction mixture was boiled for 6 h, the
solvent was removed in a vacuum, the reaction product
was isolated by column chromatography on silica gel
(eluent petroleum ether–EtOAc, 1 : 2). Yield 91%.
White powder, mp 36оС, [α]D20 +3.32 (с 0.5, acetone),
Rf 0.49 (petroleum ether–EtOAc, 1 : 2). IR spectrum,
cm–1: 3439 (ОН), 2920, 1452, 1377, 1377, 1217, 1165
(O–C–O), 1017 (C–S), 1076 (C–O), 1016, 860, 797, 636
EXPERIMENTAL
IR spectra were recorded on
a
Fourier
spectrophotometer Shimadzu IR Prestige 21 from thin
films or KBr pellets. Melting points were measured on
an instrument Gallencamp-Sanyo. NMR spectra were
registered on a spectrometer Bruker Avance–300
[300.17(1H) and 75.48 MHz (13С)], internal reference
chloroform signals. Total assignment of Н and 13С
1
signals was carried out with the use of 2D homo- (1H–
1H COSY, H–1H NOESY) and heteronuclear (1H–13C
1
HSQC, H–13C HMBC) experiments. The angle of
1
optical rotation was measured on an automated digital
polarimeter P3002RS (Kruss Co). TLC was performed
on Sorbfil plates, solvent systems CHCl3–i-PrOH,
petroleum ether–EtOAc in various ratios, development
with solution of phosphomolybdic acid or KMnO4.
Elemental analysis was carried out on an automatic
analyzer ЕА 1110 CHNS-O. All reactions were carried
out using freshly distilled solvents. For the column
chromatography silica gel Alfa Aesar (0.06–0.2 mm)
was used and the same solvent systems which were
used for TLC.
1
(C–S), 540. Н NMR spectrum(CDCl3), δ, ppm: 0.87–
0.99 m (10Н, Н4а', Mе7', Mе9', Mе10'), 1.07–1.21 m (1Н,
Н2'), 1.16–1.33 m (2Н, Н6a', H5'), 1.35 s (3Н, Me8), 1.52 s
(3Н, Me9), 1.58–1.84 m (3Н, Н4е', Н3a', Н8'), 1.88–2.06 m
(2Н, Н6е', Н3e'), 2.60–2.74 m (1Н, Н6A), 2.94–3.05 m (1Н,
Н6B), 3.17 s (1Н, OН1), 3.24 s (1Н, Н1'), 3.37 d (1Н, OН2,
J 3.1 Hz), 3.99–4.12 m (2Н, Н3, Н5), 4.41 s (1Н, Н4), 4.57
d (1H, H2, J 3.6 Hz), 6.00 d (1H, H1, J 3.6 Hz). 13C NMR
spectrum (CDCl3), δ, ppm: 20.73 (С9'), 21.04 (С10'), 22.12
(С7'), 25.80 (С3'), 26.20 (С8), 26.84 (С9), 29.94 (С5', С8'),
35.33 (С4'), 35.74 (С6), 39.96 (С6'), 46.02 (С1'), 48.64
(С2'), 67.99 (С5), 75.59 (С4), 81.76 (С3), 85.16 (С2),
105.06 (С1), 111.73 (С7). Found, %: C 60.87; H 9.17; S
8.49. C19H34O5S. Calculated, %: C 60.93; H 9.15; S 8.56.
(1S,2S,5R)-2-Isopropyl-5-methylcyclohexane-
thiol (neomenthanethiol) (А) was obtained by
procedure [11]. Yield 58%, [α]D22 +53.2 (с 0.83,
EtOН).
1,2:5,6-Di-O-isopropylidene-α-D-glucofuranose
(V) was obtained by procedure [12]. Yield 77%, [α]D20
–19.0 (с 0.36, H2O) (yield 48–59%, [α]D20 –18.5 (с not
reported, H2O) [12]).
1-Deoxy-1-[(1S,2S,5R)-2-isopropyl-5-methyl-
cyclohexylsulfanyl]-2,3:4,5-di-O-isopropylidene-β-
D-fructopyranose (II). In 3 mL of DMF was
dissolved at stirring under argon 1.3 mmol (0.224 g) of
neomenthanethiol, 1.3 mmol (0.424 g) of cesium
carbonate, and 1.3 mmol (0.48 g) of t-Bu4NI. After
5 min 1 mmol (0.37g) of 1-deoxy-1-iodo-2,3;4,5-di-О-
isopropylidene-β-D-fructopyranose (IX) was added to
the above mixture. The reaction mixture was boiled for
72 h. On cooling the solution was diluted with 10 mL
of EtOAc and washed with water (3 × 5 mL), dried
with Na2SO4, the solvent was removed in a vacuum,
the residue was separated by column chromatography
2,3:4,5-Di-O-isopropylidene-β-D-fructopyranose
(VI) was obtained by procedure [13]. Yield 85%, [α]D22
–45.6 (с 0.35, acetone) (yield 90%, [α]D20 –46.0 (с 0.36,
acetone) [13]).
1,2-O-Isopropylidene-α-D-glucofuranose (VII)
was obtained by procedure [14]. Yield 95%, [α]D20
–12.0 (с 0.32, water) (yield 80%, [α]D20 –11.8 (с not
reported, H2O) [14]).
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SYNTHESIS AND OXIDATION OF THIOGLICOSIDES
675
on silica gel (eluent petroleum ether–EtOAc, 5 : 1).
Yield 95%. White powder, mp 79оС, [α]D20 +26.8 (с
0.39, EtOH), Rf 0.44 (petroleum ether–EtOAc, 6 : 1).
IR spectrum, cm–1: 2938, 2907, 1447, 1373, 1246,
at 0°С under vigorous stirring was slowly added a
solution of 1.2 mmol (0.295 g) of 70% m-chloro-
peroxybenzoic acid in 2 mL of CHCl3. After 30 min in
event of sulfide I and 5 days in the case of sulfide II
the solvent was distilled off in a vacuum. The residue
was separated by column chromatography on silica gel
[eluent petroleum ether– EtOAc, 1 : 5 (I) and 1 : 1
(II)]. Yield of sulfoxides XI 53%, de 20%; yield of
sulfoxides XII 45%, de 36%.
1
1167 (О–С–О), 1156 (C–O), 991, 692 (C–S), 629. Н
NMR spectrum (CDCl3), δ, ppm: 0.81–0.90 m (1Н,
Н4а'), 0.88 d (3H, Mе7', J 6.4 Hz), 0.92 d (3H, Mе10', J
6.7 Hz), 0.99 d (3H, Mе9', J 6.4 Hz), 1.04–1.30 m (3Н,
H2', Н6a', H3a'), 1.37 s (3Н, Me12), 1.48 s (3Н, Me11),
1.51 s (3Н, Me9), 1.56 s (3Н, Me10), 1.65–1.81 m (3Н,
Н3e', Н4е', Н8'), 1.92–2.11 m (2Н, Н6e', Н5'), 2.79 d (1Н,
Н1A, J 13.3 Hz), 3.14 d (1Н, Н1B, J 13.3 Hz), 3.21 d
(1Н, Н1', J 1.8 Hz), 3.79 d (1Н, Н6A, J 13.0 Hz), 3.95
d.d (1Н, Н6B, J 13.0, 1.8 Hz), 4.25 d (1Н, Н5, J 8.0 Hz),
4.36 d (1H, H3,J 2.6 Hz), 4.63 d.d (1Н, Н4, J 8.0, 2.6 Hz).
13C NMR spectrum (CDCl3), δ, ppm: 16.84 (С9'), 16.99
(С10'), 18.06 (С7'), 19.97 (С12), 21.62 (С11), 21.62 (С3'),
21.82 (С5'), 22.10 (С9), 22.57 (С10), 25.85 (С8'), 31.33
(С4'), 36.49 (С6', С1), 44.62 (С1'), 45.10 (С2'), 57.50
(С6), 66.32 (С4), 66.86 (С3), 68.14 (С5), 99.02 (С2),
104.30 (С7), 104.87 (С8). Found, %:, C 64.38; H 9.58;
S 7.87. C22H38O5S. Calculated, %: C 63.73; H 9.24; S
7.73.
b. In a system tert-butylhydroperoxide−VO(acac)2.
A mixture of 1 mmol of sulfide [0.375 g (I), 0.416 g
(II)] in 5 mL of CHCl3 and 0.01 mmol (2.7 mg) of
VO(acac)2 was stirred for 5 min, and a solution of
2.5 mmol of tert-butylhydroperoxide in CHCl3 was
slowly added, the mixture was stirred for 30 min at
room temperature. After distilling off the solvent the
reaction products were isolated by column chromato-
graphy on silica gel [eluent petroleum ether– EtOAc,
1 : 5 (I) and 1 : 1 (II)]. Yield of sulfoxides XI 44%, de
19%; yield of sulfoxides XII 41%, de 12%.
c. In a system cumyl hydroperoxide–VO(acac)2. In
5 mL of CHCl3 was dissolved 1 mmol of sulfide [0.375 g
(I), 0.416 g (II)] and 0.01 mmol (2.7 mg) of VO(acac)2,
a solution of 1.1 mmol of cumyl hydroperoxide in
CHCl3 was added at stirring. After 12 h in the case of
sulfide I and 2 h in event of sulfide II the solvent was
distilled off in a vacuum. The reaction products were
isolated by column chromatography on silica gel
[eluent petroleum ether–EtOAc, 1 : 5 (I) and 1 : 1
(II)]. Yield of sulfoxides XI 40%, de 13%; yield of
sulfoxides XII 50%, de 0%.
1-Deoxy-1-[(1S,2S,5R)-2-isopropyl-5-methyl-
cyclohexylsulfanyl]-β-D-fructopyranose (X). To a
solution of 1 mmol (0.416 g) of sulfide II in 5 mL of
CHCl3 was slowly added dropwise at vigorous stirring
4 mmol (0.3 mL) of CF3COOH. After 24 h of
continuous stirring the solvent was distilled off in a
vacuum. The residue was separated by column
chromatography on silica gel (eluent CHCl3–i-PrOH,
5 : 1). Yield 62%. Brown viscous fluid, [α]D20 +37.8 (с
0.19, EtOH), Rf 0.28 (CHCH3–i-PrOH, 5 : 1). IR
spectrum, cm–1: 3385 (ОН), 2949, 2920, 1674, 1144,
1086 (C–O), 723 (C–S). 1Н NMR spectrum
(CDCl3−DMSO-d6), δ, ppm: 0.65–0.97 m (9H, Mе7',
Mе9', Mе10'), 0.77–0.87 m (1Н, Н4а'), 0.98–1.29 m (2Н,
H3a', Н6a'), 1.51–1.77 m (3Н, Н3e', Н4е', Н8'), 1.86–2.05
m (1Н, Н5'), 2.80–3.05 m (5Н, Н6e' , Н1, Н6), 3.10–3.30
m (1Н, Н2', Н1'), 3.55–3.79 m (2H, H3, Н4), 3.80–4.41
m (1Н, Н5). 13C NMR spectrum (CDCl3−DMSO-d6), δ,
ppm: 20.93 (С9'), 21.08 (С10'), 22.19 (С7'), 25.69 (С3'),
26.51 (С5'), 29.98 (С8'), 35.29 (С4'), 39.89 (С6'), 40.72
(С1), 41.55 (С6), 29.15 (С2'), 49.35 (С1'), 69.58 (С5),
71.17 (С4), 71.25 (С3), 97.08 (С2). Found, %: C 54.92;
H 8.58; S 9.17. C16H30O6S. Calculated, %: C 54.83; H
8.63; S 9.15.
6-Deoxy-6-[(RS,1S,2S,5R)-2-isopropyl-5-
methylcyclohexylsulfinyl]-1,2-O-isopropylidene-α-
D-glucofuranose (XIa). White powder, mp 140оС, [α]D20
+45.6 (с 0.43, acetone), Rf 0.20 (petroleum ether–
EtOAc, 1 : 5). IR spectrum, cm–1: 3260 (ОН), 2949,
1456, 1215, 1165 (O–C–O), 1076 (S=O), 1014, 725,
613 (C–S). 1Н NMR spectrum (CDCl3), δ, ppm: 0.87 d
(3H, Mе7', J 6.2 Hz), 0.95 d (3H, Mе9', J 6.4 Hz), 0.89–
0.98 m (1Н, Н4а'), 1.10 d (3H, Mе10', J 6.4 Hz), 1.23–
1.49 m (3Н, Н6a', H5', H2'), 1.35 s (3Н, Me8), 1.54 s
(3Н, Me9), 1.60–1.78 m (1Н, Н3a'), 1.82–2.12 m (4Н,
Н8', Н3e', Н4е', Н6e'), 2.84 t (1Н, Н6A, J 11.8 Hz), 3.23 d
(1Н, Н6B, J 11.5 Hz), 3.42 s (1Н, Н1'), 4.07 d.d (1Н, Н3
J 8.5, J 1.5 Hz), 4.29–4.47 m (1H, H4, H5), 4.56 d (1Н,
Н2, J 3.6 Hz), 4.86 br.s (1Н, OН1), 5.90 br.s (1Н,
OН2), 5.95 d (1H, H1, J 3.6 Hz). 13C NMR spectrum
(CDCl3), δ, ppm: 21.70 (С10'), 21.83 (С9'), 22.40 (С7'),
25.79 (С3'), 26.12 (С8), 26.84 (С9), 28.02 (С5'), 29.84
Oxidation of sulfides I and II. а. With m-
chloroperoxybenzoic acid. To a solution of 1 mmol
[0.375 g (I), 0.416 g (II)] of sulfide in 3 mL of CHCl3
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PESTOVA et al.
676
(С8'), 35.42 (С4'), 37.22 (С6'), 50.08 (С2'), 52.77 (С6),
61.51 (С5), 62.22 (С1'), 73.98 (С4), 83.91 (С3), 85.07
(С2), 105.48 (С1), 111.45 (С7). Found %, C 58.45; H
8.76; S 8.25. C19H34O6S. Calculated, %: C 58.43; H
8.78; S 8.21.
(С2), 109.01 (С7), 109.46 (С8). Found, %: C 61.33; H
8.87; S 7.41. C22H38O6S. Calculated, %: C 61.37; H
8.90; S 7.45.
1-Deoxy-1-[(SS,1S,2S,5R)-2-isopropyl-5-methyl-
cyclohexylsulfinyl]-2,3:4,5-di-O-isopropylidene-β-
D-fructopyranose (XIIb). White powder, mp 124оС,
[α]D20 +75.4 (с 0.12, EtOH), Rf 0.41 (petroleum ether–
EtOAc, 1 : 1). IR spectrum, cm–1: 2947, 1105 (O–C–O),
6-Deoxy-6-[(SS,1S,2S,5R)-2-isopropyl-5-methyl-
cyclohexylsulfinyl]-1,2-O-isopropylidene-α-D-gluco-
furanose (XIb). White powder, mp 154оС, [α]D20 +46.2
(с 0.39, acetone), Rf 0.32 (petroleum ether–EtOAc,
1 : 5). IR spectrum, cm–1: 3318 (ОН), 1217, 1163
(O–C–O), 1074 (S=O), 1011, 889, 795, 617 (C–S). 1Н
NMR spectrum (CDCl3), δ, ppm: 0.89 d (3H, Mе7', J
6.4 Hz), 0.91 d (3H, Mе10', J 5.1 Hz), 0.88–0.98 m
(1Н, Н4а'), 1.00 d (3H, Mе9', J 6.4 Hz), 1.25–1.47 m
(3Н, Н6a', H3a', H2'), 1.35 s (3Н, Me8), 1.52 s (3Н,
Me9), 1.67–1.82 m (1Н, Н8'), 1.83–1.97 m (2Н, Н3e',
Н4е'), 1.98–2.19 m (1Н, Н5'), 2.50 d (1Н, Н6e', J
14.4 Hz), 2.98 d.d (1Н, Н6A J 13.5, 1.5 Hz), 3.06 br.s
(1Н, Н1'), 3.16 d.d (1Н, Н6B, J 13.1, 9.8 Hz), 3.91 br.s
(1Н, OН1), 4.06 d.d (1Н, Н3 J 8.5, J 2.6 Hz), 4.4 d (1Н,
Н4, J 2.3 Hz), 4.54–4.69 m (1H, H2, H5), 5.02 br.s (1Н,
OН2), 5.96 d (1H, H1, J 3.6 Hz). 13C NMR spectrum
(CDCl3), δ, ppm: 21.21 (С9'), 21.57 (С10'), 22.75 (С7'),
26.18 (С3'), 26.18 (С8), 26.86 (С9), 27.80 (С5'), 29.42
(С8'), 34.12 (С6'), 34.95 (С4'), 47.63 (С2'), 53.36 (С6),
59.53 (С1'), 67.40 (С5), 74.41 (С4), 83.05 (С3), 85.15
(С2), 105.25 (С1), 111.68 (С7). Found, %:, C 58.41; H
8.75; S 8.23. C19H34O6S. Calculated, %: C 58.43; H
8.78; S 8.21.
1
1057 (S=O), 1028 (C–O), 763, 677 (C–S). Н NMR
spectrum (CDCl3), δ, ppm: 0.88 d (3H, Mе7', J 6.4 Hz),
0.85–0.96 m (1Н, Н4а'), 0.95 d (3H, Mе10', J 6.7 Hz),
1.01 d (3H, Mе9', J 6.4 Hz), 1.20–1.45 m (2Н, Н6a',
Н2'), 1.38 s (3Н, Me12), 1.43 s (3Н, Me11), 1.53 s (3Н,
Me9), 1.55 s (3Н, Me10), 1.59–1.72 m (1Н, H3a'), 1.75–
1.92 m (2Н, Н3e', Н4е'), 1.92–2.04 m (1Н, Н8'), 2.16–2.42
m (1Н, Н5'), 2.51 d (1Н, Н6e', J 14.5 Hz), 3.05 s (1Н,
Н1'), 3.31 d (1Н, Н1A, J 13.5 Hz), 3.38 d (1Н, Н1B, J
13.5 Hz), 3.75 d (1Н, Н6A, J 13.1 Hz), 3.98 d.d (1Н,
Н6B, J 13.1, 1.8 Hz), 4.25 d (1Н, Н5, J 8.0 Hz), 4.38 d
13
(1H, H3, J 2.6 Hz), 4.64 d.d (1H Н4, J 7.8, 2.7 Hz). C
NMR spectrum (CDCl3), δ, ppm: 21.43 (С9'), 21.51 (С10'),
23.05 (С7'), 24.26 (С12'), 24.99 (С9), 25.97 (С11), 26.23
(С10), 26.34 (С3'), 27.67 (С5'), 29.43 (С8'), 34.60 (С6'),
35.35 (С4'), 48.32 (С2'), 57.30 (С1'), 61.57 (С1), 62.09
(С6), 70.39 (С4), 70.52 (С3), 73.12 (С5), 101.71 (С2),
108.80 (С7), 109.45 (С8). Found, %: C 61.33; H 8.89; S
7.42. C22H38O6S. Calculated, %: C 61.37; H 8.90; S 7.45.
The authors express their gratitude to the
researchers of the laboratory of physicochemical
research of Institute of Chemistry of Komi Scientific
Center of Ural Branch, Russian Academy of Sciences,
E.N. Zainullina, S.P. Kuznetsov, I.N. Alekseev for
registering NMR spectra and to E.U. Ipatova for
recording IR spectra.
1-Deoxy-1-[(RS,1S,2S,5R)-2-isopropyl-5-methyl-
cyclohexylsulfinyl]-2,3:4,5-di-O-isopropylidene-β-
D-fructopyranose (XIIa). White powder, mp 139оС,
[α]D20 +87.9 (с 0.09, EtOH), Rf 0.45 (petroleum ether–
EtOAc, 1 : 1). IR spectrum, cm–1: 2943, 1166 (O–C–O),
1
1109 (C–O), 1452, 1056 (S=O), 756, 692 (C–S). Н
NMR spectrum (CDCl3), δ, ppm: 0.84 d (3H, Mе7', J
6.4 Hz), 0.91 d (3H, Mе10', J 6.7 Hz), 0.95–1.06 m (1Н,
Н4а'), 1.07 d (3H, Mе9', J 6.4 Hz), 1.19–1.33 m (1Н,
Н6a'), 1.37 s (3Н, Me12), 1.33–1.47 m (1Н, Н2'), 1.51 s
(3Н, Me11), 1.53 s (3Н, Me9), 1.59 s (3Н, Me10), 1.68–
1.83m (2Н, H3a', H5'), 1.84–2.01 m (3Н, Н6e', Н4е', Н3e'),
2.15–2.30 m (1Н, Н8'), 3.11 d (1Н, Н1A J 13.6 Hz), 3.41
d (1Н, Н1B, J 13.6 Hz), 3.43 s (1Н, Н1'), 3.75 d (1Н,
Н6A, J 13.1 Hz), 3.98 d. d (1Н, Н6B, J 13.0, 1.8 Hz),
4.24 d (1Н, Н5, J 8.0 Hz), 4.58–4.75 m (1H, H3, Н4).
13C NMR spectrum (CDCl3), δ, ppm: 22.07 (С9'), 22.22
(С10'), 22.36 (С7'), 23.92 (С12), 25.28 (С9), 25.72 (С3'),
26.02 (С11), 26.56 (С10), 27.56 (С5'), 28.95 (С8'), 35.59
(С4'), 36.99 (С6'), 50.62 (С2'), 61.25 (С1'), 61.84 (С1),
62.31 (С6), 70.15 (С4), 70.50 (С3), 72.64 (С5), 101.53
The study was carried out under the financial
support of the Russian Foundation for Basic Research
(grant no.13-03-01312_а) and of the Ural Branch,
Russian Academy of Sciences (12-U-3-1015).
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