Enantiospecific synthesis and insect feeding activity of sulfur-containing cyclitols

Article abstract of DOI:10.1016/j.carres.2008.09.026

The first syntheses of two deoxythiocyanocyclitols (4-deoxy-4-thiocyano-l-chiro-inositol and deoxythiocyanoconduritol F) and two deoxysulfonylcyclitol acetals are reported by a chemoenzymatic enantioselective route. The compounds were prepared by a sequen

Full text of DOI:10.1016/j.carres.2008.09.026

Carbohydrate Research 344 (2009) 44–51
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Enantiospecific synthesis and insect feeding activity
of sulfur-containing cyclitols
Ana Bellomo a, Soledad Camarano b, Carmen Rossini b, David Gonzalez a,
*
a Laboratorio de Síntesis Orgánica, D.Q.O, Fac. de Química, Univ. de la República, C.C. 1157 Montevideo, Uruguay
b Laboratorio de Ecología Química, D.Q.O.—DepBio, Fac. de Química, Univ. de la República, C.C. 1157 Montevideo, Uruguay
a r t i c l e i n f o
a b s t r a c t
Article history:
The first syntheses of two deoxythiocyanocyclitols (4-deoxy-4-thiocyano-L-chiro-inositol and deoxythio-
Received 15 August 2008
Received in revised form 18 September
2008
Accepted 23 September 2008
Available online 30 September 2008
cyanoconduritol F) and two deoxysulfonylcyclitol acetals are reported by a chemoenzymatic enantiose-
lective route. The compounds were prepared by a sequence of enzymatic and ruthenium-catalyzed
dihydroxylations, and the results were studied regarding reaction conditions and co-catalyst for different
derivatives. The new compounds were included in a minilibrary of deoxygenated cyclitols and evaluated
for their capacity to influence the feeding behavior of Epilachna paenulata (Coleoptera: Coccinellidae), a
common pest of the Curcubitaceae crops.
Keywords:
Thiocyanodeoxycyclitol
Dihydroxylation
Ó 2008 Elsevier Ltd. All rights reserved.
Insect feeding behavior
1. Introduction
chemoenzymatic routes for the preparation of epi-inositol,2 (ꢀ)-
conduramine C-4,3 phenylthioconduritol F,4 hydroxythiocyanates,
Cyclitols are a group of molecules of particular interest among
those in the carbohydrate family of compounds. The biological
activity of these compounds, and particularly their role in
intracellular communication, has been extensively studied and
summarized.1 In our laboratory, we have developed efficient
and episulfides.5 The common starting material for all of these syn-
theses is the homochiral metabolite 1 produced by whole-cell
asymmetric dihydroxylation of bromobenzene with toluene dioxy-
genase (TDO) (Fig. 1).6,7 In a continuation of our previous studies
on the ring opening of vinyl oxiranes with sulfur compounds,4,5
Br
Br
OH
OH
O
O
PhS
NCS
TDO expressed
in P. putida 39/D
OH
OH
conduritol
hydroxythiocyanates
> 99 ee
phenylthioconduritol F
OH
Br
Br
OH
HO
organic
OH
OH
OH
OH
O
O
synthesis
H2N
OH
HO
OH
S
OH
epi-inositol
1
(-)-conduramine C-4
conduritol episulfide
derivatives
Figure 1. Chemoenzymatic synthesis of cyclitols from bromobenzene.
* Corresponding author. Tel.: +598 2 9290106; fax: +598 2 9241906.
E-mail address: davidg@fq.edu.uy (D. Gonzalez).
0008-6215/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2008.09.026

A. Bellomo et al. / Carbohydrate Research 344 (2009) 44–51
45
we now wish to report the results obtained for the preparation of
unnatural cyclitol derivatives containing a –SCN and SO2Ph group.
We considered the synthesis of these previously unreported
molecules based on their similarity to a number of cyclitol deriva-
tives exhibiting antifeedant, antibiotic, antileukemic, and growth-
regulating activity.8,9 In view of their biological potential, we
tested some of the cyclitol derivatives as feeding deterrents against
Epilachna paenulata (Coleoptera: Coccinellidae). Those results, the
synthesis of the new sulfur-containing derivatives, and in parti-
The reactivity of the olefin toward two dihydroxylating reagents
(OsO4/NMO and RuCl3/NaIO4) under different reaction conditions
was studied, and the results are summarized in Table 1. Attempts
at the cis-dihydroxylation of 4 using a catalytic amount of osmium
tetraoxide in the presence of N-methylmorpholine N-oxide as co-
oxidant were unsuccessful as shown in entries 1 and 2. Experi-
ments utilizing stoichiometric amounts of OsO4 consumed the
starting material in 24 h. However, only minute amounts of the de-
sired product were obtained even after 24 h of reaction time (entry
3). In addition, the high cost of OsO4, its volatility, toxicity, and the
cumbersome recovery of the compound, was not appealing; there-
fore, we abandoned this methodology.
cular the total synthesis of a thiocyanodeoxy
disclosed here.
L-chiro-inositol are
In 1994, Shing reported a dihydroxylation using catalytic
amounts of ruthenium tetraoxide.14 RuO4 is isoelectronic to OsO4,
and several reports in the literature describe its use as an effective
and greener alternative for the dihydroxylation of unreactive
alkenes.15–17 In particular, Hudlicky and Desjardins described the
2. Results and discussion
2.1. Chemistry
To access our target, we proceeded according to the traditional
strategy, oxygenation of the cis-dienediol 1.6 The diol was pro-
tected as its corresponding acetonide and the more reactive unsub-
Table 1
stituted double bond was epoxidized to furnish the
a-oxirane
Dihydroxylation of thiocyanoconduritol 4
2.10–13 Radical dehalogenation and treatment with ammonium
thiocyanate gave thiocyanohydrin 4 as we previously described.5
Attempts to prepare 4 by radical dehalogenation of hydroxythio-
cyanate 5 using AIBN or azobiscyclohexane carbonitrile (ABCC)
failed. Loss of the thiocyanate group by the action of Bu3SnH was
unavoidable, and therefore compound 613 was obtained as the only
identified product in this reaction (Scheme 1).
Entry Conditions
T (°C) Time
Isolated yield
(%)
1
2
3
4
5
Catalytic OsO4–NMO
rt
40
rt
ꢀ25
2 days
1 day
1 day
10 min No reaction
20 min No reaction
10 min No reaction
20 min No reaction
No reaction
No reaction
8 (trace)
Stoichiometric OsO4
Catalytic RuCl3 (6%)–NaIO4
(1.5 equiv)
6
7
ꢀ12
Acetonide 4 was deprotected to render 4-deoxy-4-thiocyano-
conduritol F (7), the first described SCN-containing deoxyconduri-
tol. Importantly, intermediate 4 was dihydroxylated affording the
oxidation level of an inositol, followed by acetonide deprotection
to provide the deoxyinositol 8 (Scheme 2).
8
9
10
0
0
0
3 min
9 min
15 min 8 (82)
8 (trace)
8 (23)
Br
Br
O
O
O
(d)
O
O
(c)
OH (a) and (b)
O
NCS
O
OH
O
OH
4
1
2
3
ref. 5
Br
Br
(e)
O
O
O
O
NCS
OH
6
OH
5
Scheme 1. Synthesis of thiocyanohydrin 4 and compound 6. Reagents and conditions: (a) DMP, p-TsOH, acetone, rt, 95%; (b) m-CPBA, CH2Cl2, rt, 80%; (c) Bu3SnH, ABCC, THF,
reflux, 4 h, 70%; (d) NH4SCN, CH3CN, 1 h, 85%; (e) Bu3SnH, AIBN, THF, reflux, 2 h, 50%.
OH
OH
HO
OH
OH
HO
OH
OH
O
O
(a)
(c)
(b)
4
NCS
NCS
NCS
OH
OH
OH
7
9
8
Scheme 2. Synthetic route developed toward thiocyanocondurtiol F (7) and 6-thiocyanodeoxy
L-chiro-inositol (9). Reagents and conditions: (a) RuCl3–NaIO4, AcOEt–CH3CN–
H2O, 15 min, 82%; (b) Dowex 50 (H+), MeOH–H2O, rt, 1 h, 93%; (c) Dowex 50 (H+), MeOH–H2O, rt, 24 h, 90%.

46
A. Bellomo et al. / Carbohydrate Research 344 (2009) 44–51
dihydroxylation of a conduritol acetal with an RuCl3–NaIO4 mix-
ture in their synthesis of allo-inositol.18 It is known that RuO4
can rapidly cleave C@C bonds.19,20 However, the nucleophilic
addition of water to the intermediate ruthenate is faster in a
3:3:1 mixture of EtOAc, acetonitrile, and water. Any other solvent
combination facilitated the scission reaction.19 As a consequence,
we choose this ternary solvent mixture as a starting point. Oxida-
tion of 4 using RuCl3 and NaIO4 (as co-oxidant) furnished syn-diol 8
with complete reaction within 15 min as described in entry 10 (Ta-
ble 1). All attempts to run the reaction below 0 °C resulted in the
complete recovery of the starting material (entries 4–7). Dihydr-
oxylation under kinetic control overwhelmingly favored the for-
mation of the less hindered
(Scheme 2).
L-chiro-inositol substitution pattern
Deprotection of 8 under acidic conditions rendered 9 in 36%
overall yield from compound 1. Analysis of the 1H and 1H-COSY
spectra of the protected inositol 8 identified to be it stereochemi-
cally analogous to L-chiro-inositol. The spectra of this compound
showed that the key proton H4 (cyclitol numbering) is coupled
with a large diaxial coupling constant to the neighboring protons
H3 and H5 (Table 2). The measured coupling constants are in good
agreement with the corresponding large torsion angles (175°, 174°,
and 140°) calculated using the Karplus equation for the AM1 min-
imized structure of 8 shown in Figure 2.
The successful dihydroxylation of 4 prompted us to study the
reactivity of the protected derivative of 4-deoxy-4-(phenyl-
thio)conduritol F (10) (Scheme 3).4 We reasoned that 10 could be
selectively oxidized to obtain the protected derivative of 4-
Table 2
Experimental coupling constants of acetonide 8
H’s
Multiplicity
Experimental values J’s (Hz)
deoxy-4-(phenylthio)-L-chiro-inositol (14). However, 10 did not
H1
H2
H3
H4
H5
H6
OH3
OH5
OH6
dd
dd
ddd
t
ddd
dt
d
3.1 (H1–H6); 5.4 (H1–H2)
5.4 (H2–H1); 5.8 (H2–H3)
10.6 (H3–H4); 6.1 (H3–H2); 6.0 (H3–OH3)
10.2 (H4–H3); 10.2 (H4–H5)
3.2 (H5–H6); 9.8 (H5–H4); 6.8 (H5–OH5)
3.2 (H6–H5); 3.1 (H6–H1); 3.1 (H6–OH6)
6.0 (OH–H3)
render the expected dihydroxylated compound as deduced from
the 1H NMR data. In fact, the reaction afforded three products
(Table 3, entry 1) corresponding to the diastereomeric mixture of
sulfoxides 11 and the sulfone 12 as shown in Scheme 3.
Since there were two oxidants involved in the reaction, we
decided to determine which of them was responsible of the sulfide
oxidation. In order to study the effect of the co-oxidant, we per-
formed the reaction using 1.5 equiv of NaIO4 in the absence of
d
d
6.9 (OH–H5)
3.8 (OH–H6)
Table 3
Dihydroxylation of compound 10
Entry Conditions
T
(°C)
Time
Isolated
yield (%)
1
Catalytic RuCl3 (6%)–NaIO4
0
30 min 11 (19) 12 (42)
(1.5 equiv)
2
3
NaIO4 (1.5 equiv)
0
10 min No reaction
20 min No reaction
4
5
6
3 h
4 h
24 h
11 (trace)
11 12 (trace)
12
NaIO4 (3.0 equiv)
rt
7
8
9
10
11
RuCl3 (8%)–NaIO4 (2.0 equiv)
RuCl3 (10%)–NaIO4 (2.0 equiv)
RuCl3 (15%)–NaIO4 (2.0 equiv)
RuCl3 (30%)–NaIO4 (2.0 equiv)
RuCl3 (6%)–t-BuOOH (2.0 equiv)
0
0
0
0
0
rt
rt
30 min 12 (56) 13 (29)
30 min 12 (43)a
30 min 12 (50)a
30 min 12 (50)a
2 h
1 h
Recovery s.m. 11
(trace)
12
RuCl3 (8%)–t-BuOOH (2.0 equiv)
24 h
Recovery s.m. 11 (13)
a
In these cases, 12 is obtained along with a complex mixture of polar compounds
Figure 2. Minimized structure of 4-deoxy-4-thiocyano-
L
-chiro-inositol dimethyl
that could neither be isolated in the pure state nor identified.
acetal.
different dihydroxylation
conditions
O
ref.4
see Table3
2
O
S
Ph
OH
10
OH
OH
O
O
O
HO
HO
O
O
O
O
O
O
O
O
S
S
O
O
S
S
Ph
OH
OH
Ph
Ph
OH
OH
Ph
11
12
13
14
diasteromeric
mixture
Scheme 3. Oxidation of compound 10. The deoxy inositol derivative 14 was never detected in the reaction mixtures.

A. Bellomo et al. / Carbohydrate Research 344 (2009) 44–51
47
RuCl3 (Table 3, entries 2–4). Under these conditions even after 3 h,
2.2. Biological studies
only minute amounts of 11 were formed. The diastereomeric mix-
ture of sulfoxides had identical chromatographic properties, and
the individual isomers could not be isolated in the pure state.
When we then performed several microscale screening reactions,
for example, by increasing the amount of NaIO4 (3.0 equiv), we iso-
lated either a mixture of 11 and 12 after 4 h (entry 5) or the sulfone
12 as the only product after 24 h (entry 6). From these experiments
it is clear that compound 12 is formed from 11 by a stepwise
sequential oxidation.
In order to study the effect of the amount of NaIO4 in the pres-
ence of RuCl3, we carried out several experiments with various
combinations of oxidant and co-oxidant. The results shown in
entries 7–11 indicated that inositols were formed, but concomitant
oxidation of the sulfur atom was unavoidable with these reagents.
The results indicated that the dihydroxylation of the olefin was not
attainable without altering the sulfur oxidation state. However,
this route seems an appealing route toward inositol sulfoxides
and particularly sulfones.
2.2.1. Feeding activity assay: option bioassay using E. paenulata
(Coleoptera: Coccinellidae)
This bioassay tests feeding deterrence or stimulation of a com-
pound against a special herbivorous insect, E. paenulata. Indexes of
variability in feeding activity (IFA) were calculated, and the results
obtained are shown in Table 4. Preference for the control or the
treatment is depicted in Figure 4.
The outcomes of this test revealed that compounds 9, 15, 16, 17,
and 18 were active (p <0.05). Compounds 9, 15, and 17 showed
deterrent activity (0 < IFA < 1), while compound 16 and 18 had
the opposite phagoestimulant activity (ꢀ1 < IFA < 0).
Some conclusions can be drawn from this preliminary screen-
ing. While sugars and inositols are usually phagostimulants and
are well tolerated,22 substituted deoxygenated inositols can exert
a deterrent or phagostimulant effect depending on the nature
Interestingly, inositol derivative 13 is better obtained with a rel-
atively low load of the catalytic oxidant (8 mol %, entry 7). Using a
lower (6 mol %, entry 1) or higher (10, 15, 30 mol %, entries 8–10)
amount did not render any dihydroxylated product. While it is dif-
ficult to justify the great disparity in product formation based on
the stated and subtle variance in the RuCl3 catalyst loading, these
results were repeatable and occurred when using the same lots
of the indicated chemicals.
In a final effort to enable chemoselective oxidation of the olefin
in the presence of a thiophenyl residue, we tested tert-butyl-
hydrogen peroxide as an alternative stoichiometric oxidant
(entries 11–12). tert-Butylhydroperoxide is less reactive than per-
iodate since it did not render any product at 0 °C in the presence
of 6 mol % RuCl3. When the reaction was warmed up to room tem-
perature, trace amounts of sulfoxide 11 were formed. Increasing
the amount of RuCl3 to 8 mol % (which had caused a dramatic
change when used in combination with NaIO4) did not yield any
sulfone or dihydroxylated products but did again form the sulf-
oxide 11 in 13% yield.
Table 4
Index of variability in feeding activity calculated for the compounds tested
Compound
Activity (p values)a
IFAb
7
9
None (0.440)
0.6 0.2
Deterrent (0.012)
Deterrent (0.028)
Phagostimulant (0.029)
Deterrent (0.048)
Phagostimulant (0.002)
None (0.233)
0.90 0.04
0.82 0.05
ꢀ0.71 0.08
0.7 0.1
15
16
17
18
19
20
21
ꢀ0.8 0.1
0.4 0.1
None (0.370)
None (0.172)
0.3 0.2
0.7 0.1
a
p values from Wilcoxon Rank Test.
standard error (IFA).
b
Overall, these results indicate that successful dihydroxylation of
the olefin is dependant of a delicate balance between the stoichi-
ometric oxidant and its ratio to the catalytically active ruthenium.
According to our results, the combination of 8 mol % RuCl3 and
2 equiv of NaIO4 is the best fit to achieve the task, although it can-
not selectively oxidize the double bond in the presence of the thio-
phenyl moiety.
As part of our program for the synthesis of cyclitol derivatives to
be evaluated for their biological properties, we prepared a small
library of analogs (Fig. 3), which was tested for deterrent activity.
Figure 4. Feeding preferences of E. paenulata between control (h) and leaves
treated with cyclitol derivatives (j). Bars show standard error; denotes significant
differences (Wilcoxon Rank Test).
*
OH
OH
Br
Br
OH
OH
HO
OH
OH
OH
OH
OH
NCS
OH
S
O
NCS
NCS
OH NCS
O
OH
OH
OH
OH
OH
7
9
15
16
17
Br
Br
Br
Br
OH
OH
OH
OH N3
OH
OH
OH
S
S
OH H2N
OH
OH
OH
OH
18
19
20
21
Figure 3. Cyclitols tested for biological activity.

48
A. Bellomo et al. / Carbohydrate Research 344 (2009) 44–51
and stereochemistry of the substituent. In general, it was observed
that sulfur-containing cyclitols (9, 15, 16, 17, and 18) were more
active than nitrogen analogs 20 and 21. Compounds 9, 15, and
17 are deterrents, and derivatives 16 and 18 are phagostimulants.
The only fully oxygenated analog tested was SCN-inositol 9, which
exhibited the highest deterrent activity (IFA = 0.90 0.04, p =
0.012), and is more active than the corresponding conduritols 7
and 15. Although 7 showed a tendency toward deterrent activity,
the effect was not significant (IFA = 0.6 0.2, p = 0.440); therefore,
it appears that the presence of a bromine atom in 15 causes a dif-
ference with the dehalogenated analog thiocyanoconduritol 7. On
the other hand, bromothiocyanodeoxyconduritol 16, which is dia-
stereomeric with 15 but otherwise has the same substitution pat-
tern, induced a completely opposite behavior on E. paenulata.
Indeed, while 16 was phagoestimulant (IFA = ꢀ0.71 0.08, p =
0.029), 15 was deterrent (IFA = 0.82 0.05, p = 0.028). Compound
17, the only sulfone tested, was shown to be significantly deterrent
(IFA = 0.7 0.1, p = 0.048). We assayed two diasteromeric phenyl-
thioconduritols (18 and 19). The b-thiophenylconduritol was
phagoestimulant (IFA = ꢀ0.8 0.1, p = 0.002), but its diastereo-
mer 19 did not show any significant effect according to the Wilco-
xon Rank Test. Overall, we have found that several sulfur-
recorded on a Bruker Avance DPX-400 instrument. Chemical shifts
(d) are given in parts per million downfield from tetramethylsilane,
and coupling constants (J) are reported in hertz. Low-resolution
mass spectra were performed on a Hewlett–Packard 5890 instru-
ment-mass detector 5971, using the electron-impact mode and
molecular ion peaks which are listed with relative abundances.
Elemental analyses were recorded on a Fisons EA 1108 CHNS-O
analyzer. High-resolution mass spectra were performed on a
Bruker Daltonics spectrometer model MicrO TofQ (ESI + mode).
Analytical TLC was performed on silica gel 60F-254 plates and
visualized with UV light (254 nm) and/or anisaldehyde–
H2SO4–AcOH as detecting agent. Flash column chromatography
was performed in silica gel (Kieselgel 60, EM Reagents, 230–
400 mesh).
4.1.1. (1S,2S,3S,6S)-2,3-Isopropylidendioxy-6-
thiocyanatocyclohex-4-ene-1-ol (4)
A solution of epoxide 3 (0.105 g, 0.627 mmol) in acetonitrile
(2.0 mL) was treated with NH4SCN (0.238 g, 3.130 mmol) at room
temperature. The reaction mixture was stirred for 4 h until con-
sumption of the starting material as monitored by TLC. The solvent
was evaporated under reduced pressure, and the residue was di-
luted with CH2Cl2 and sequentially washed with satd aq NH4Cl,
and aq NaCl. The organic layer was dried (anhyd Na2SO4) and evap-
orated to afford a crude oily product that was purified by flash col-
umn chromatography (70:30 hexane–EtOAc). Colorless oil (62%);
containing cyclitols, and particularly L-chiro-inositol 9, are active
and can influence the dietary behavior of E. paeneulata in this op-
tion test. The results suggest that carefully designed carbohydrate
analogs could be of potential use in the control of specific
herbivores.
½
a 2D0
+137 (c 0.85, CH2Cl2); IR (neat): 3650–3150 (OH, w), 2155
ꢁ
(SCN, s), 1063 (C–O–C, s); 1H NMR (CDCl3): d 6.08 (dd, 1H, J4,5
10.0, J4,3 3.7 Hz, H-4), 5.95 (br dd, 1H, J5,4 10.0, J5,6 1.3, H-5), 4.66
(br t, 1H, J3,2 5.0, J3,4 4.8, H-3), 4.14 (dd, 1H, J2,1 8.0, J2,3 5.1, H-2),
3.81 (t, 1H, J1,2 8.2, J1,6 8.4, H-1), 3.70 (dq, 1H, J6,1 8.5, J6,5 1.9, H-
6), 3.50 (br s, 1H, OH), 1.52 (s, 3H, CH3), 1.41 (s, 3H, CH3); 13C
NMR (CDCl3): d 129.0 (C (H-4)), 128.1 (C (H-5)), 111.2 (SCN),
111.1 (C isopropylidene), 78.3 (C (H-2)), 72.3 (C (H-1) and C (H-
3)), 49.8 (C (H-6)), 28.5 (CH3), 26.2 (CH3). EIMS: 212 (M+ꢀCH3,
78), 169 (M+ꢀSCN, 13), 151 (M+ꢀC3H6O–H2O, 21), 58 (SCN, 4);
Anal. Calcd for C10H13NO3S: C, 52.85; H, 5.77; N, 6.16. Found: C,
52.89; H, 5.95; N, 5.95.
3. Conclusions
In conclusion, we have reported the synthesis of a SCN-inositol
with the L-chiro configuration. Ruthenium catalysis allowed the
dihydroxylation of 4 giving a feasible route toward SCN-containing
inositols, while osmium tetroxide was unreactive with these types
of alkenes. The reaction is under strict steric control furnishing 9
(after deprotection) with excellent facial selectivity. Furthermore,
deprotection of 4 rendered the previously unknown thiocyanocon-
duritol F (7) in excellent yield. However, we were unable to estab-
lish the best conditions that would lead to the preparation of
phenylthioinositol 14; instead phenylsulfonylinositol 13 was ob-
tained in moderate yield. Overall, our study has disclosed the first
available data on the oxidation of sulfur-containing conduritols
and their delicate chemistry.
4.1.2. (1S,2S,3R)-4-Bromo-2,3-isopropylidenecyclohex-5-ene-1-
ol (6)13
Tri-n-butyltin hydride (0.1 mL, 0.504 mmol) was added to a
mixture of azoisobutyronitrile (AIBN, 44.3 mg, 0.27 mmol) and
compound 5 (84.8 mg, 0.277 mmol) in dry THF (10.0 mL). The reac-
tion mixture was refluxed for 2 h. Concentration at reduced pressure
and purification of the oily residue by flash chromatography (70:30
hexane–EtOAc) furnished the pure product 6 as a white solid (50%).
IR (neat): 3600–3200 (OH, w), 2070 (s), 1381, 1074; 1H NMR (CDCl3):
d 6.17 (dd, 1H, J5,CH2 3.6 and 3.7, H-5), 4.67 (d, 1H, J3,2 5.9, H-3), 4.14
(t, 1H, J2,3 6.2, J2,1 6.9, H-2), 3.96 (m, 1H, H-1), 2.50 (dt, 1H, J6,5 4.7,
JCH2 12.6, H-6 (CH2)), 2.15 (m, 2H, H-6 (CH2) and OH), 1.52 (s,
CH3), 1.44 (s, CH3); 13C NMR (CDCl3): d 130.0 (C (H-5)), 119.9 (C–
Br), 110.3 (C isopropylidene), 79.3 (C (H-2)), 77.1 (C (H-3)), 68.1 (C
(H-1)), 32.3 (C (H-6)), 28.5 (CH3), 27.2 (CH3). (1H and 13C NMR spec-
tral data matched that reported.13) EIMS: 235 ((M++2)ꢀCH3, 75), 233
(M+ꢀCH3, 74), 175 ((M++2)ꢀC3H6O–H2O, 48), 173 (M+ꢀC3H6O–H2O,
46), 94 (M+ꢀBr–C3H6O–H2O, 100).
Some of the cyclitols synthesized showed biological activity
when subjected to the assay performed. In particular, thiocyanode-
oxyinositol 9 proved to be a potential leader for the development
of insect deterrents of high selectivity.
4. Experimental
4.1. General
All non-hydrolytic reactions were carried out under a nitrogen
atmosphere, with standard techniques for the exclusion of mois-
ture. All solvents were purified prior to use. The commercially
available reagents were purchased from Sigma–Aldrich and used
without further purification. Optical rotations were measured
using a Zuzi 412 automatic polarimeter with a 7-mL cell and a
Kruss Optronic GmbH P8000 polarimeter with a 0.5-mL cell (con-
centration c given as g/100 mL). Melting points were determined
on a Gallenkamp apparatus and on a Fisher–Johns apparatus, and
are uncorrected. Infrared spectra were recorded using a Shimadzu
FTIR 8101A spectrometer, and peaks are reported in reciprocal cm
along with relative signal intensities and characteristics: s (strong);
m (medium); w (with). Nuclear magnetic resonance spectra were
4.1.3. (1S,2S,3S,6S)-6-Thiocyanatocyclohex-4-ene-1,2,3-triol (7)
A mixture of compound 4 (0.032 g, 0.143 mmol), Dowex-50 (H+
form) resin (0.35 g), and MeOH–H2O (2.0 mL–0.5 mL) was stirred
at room temperature for 24 h. After completion of the reaction,
One equivalent of AIBN was required to complete the reaction in spite of the fact
that theoretically only a catalytic amount must suffice.

A. Bellomo et al. / Carbohydrate Research 344 (2009) 44–51
49
the resin was filtered off and the solvent was evaporated under re-
duced pressure. Purification by flash chromatography (20:80 hex-
ane–EtOAc) rendered optically active 7 as a white crystalline
chromatography (50:50 hexane–EtOAc), affording compounds 11
(19%) as an oil and 12 (42%) as a white solid.
solid (90 %). Mp 81–83 °C; ½a D20
ꢁ
+209 (c 0.74, MeOH); IR (KBr):
4.2.1. (1S,2R,3R,6S)-2,3-Isopropylidendioxy-6-(phenylsulfinyl)-
3730–3042 (OH, w), 2157 (SCN, s), 1094 (s); 1H NMR (MeOD): d
6.02 (dq, 1H, J4,5 10.0, J4,3 4.4, J4,6 2.3, H-4), 5.84 (dd, 1H, J5,4 9.9,
J5,6 2.4, H-5), 4.24 (t, 1H, J3,2 4.5, J3,4 4.4, H-3), 3.91 (br t, 1H, J1,2
9.5, J1,6 8.2, H-1), 3.75 (ds, 1H, J6,1 8.0, J6,5 2.3, J6,4 2.3, H-6), 3.57
(dd, 1H, J2,1 9.5, J2,3 4.1, H-2); 13C NMR (MeOD): d 131.3 (C (H-
4)), 127.7 (C (H-5)), 111.4 (SCN), 72.7 (C (H-2)), 70.8 (C (H-1)),
66.36 (C (H-3)), 52.9 (C (H-6)). Anal. Calcd for C7H9NO3S: C,
44.91; H, 4.85; N, 7.48; S, 17.13. Found: C, 44.95; H, 4.65; N,
7.41; S, 17.23.
cyclohex-4-ene-1-ol (1:1 mixture of epimeric sulfoxides) (11)
½
a 2D0
+85 (c 0.23, MeOH); IR (KBr): 3500–3200 (OH, w), 1603
ꢁ
(sulfoxide, s); EIMS: 279 (M+ꢀCH3, 8), 167 (M+ꢀSPh–H2O, 31),
149 (M+ꢀSPh–2H2O, 100); 1H RMN (CDCl3): 1H NMR (CDCl3): d
7.75 (br dd, 2H, J 7.8, J 1.7, H arom.), 7.65 (dd, 2H, J 7.7, J 1.7, H
0
0
0
0
arom.), 7.58 (m, 6H, H arom.), 6.08 (tdd, 2H, J4-5/4 -5 9.8, J4-3/4 -3
6.0, H-4 and H-40), 5.55 (td, 2H, J5,4/5 ,4 9.9, J5,6/5 ,6 1.8, H-5 and
0
0
0
0
H-50), 4.59 (br t, 2H, J3,4/3 ,4 5.2, J3,2/3 ,2 5.2, H-3 and H-30), 4.16
0
0
0
0
(dd, 2H, J2,3/2 ,3 4.8, J2,1/2 ,1 6.4, H-2 and H-20), 4.05 (td, 2H, J1,6/1 ,6
0
0
0
0
0
0
7.2, J1,2/1 ,2 6.8, JH1,OH/H1 ,OH 2.0, H-1 and H-10), 3.92 (d, 1H, JOH,H1/
0
0
0
2.0, OH (H-1) or OH (H-10)), 3.68 (d, 1H, JOH,H1/OH,H1 2.0, OH
0
OH,H10
4.1.4. (1R,2R,3R,4S,5S,6S)-3,4-Isopropylidendioxy-6-
thiocyanatocyclohexane-1,2,5-triol (8)
(H-1) or OH (H-10)), 3.63 (dq, 1H, J6,5/6 ,5 2.0, J6,1/6 ,1 7.6, H-6 or
0
0
0
0
0
0
0
0
A stirred solution of 4 (0.106 g, 0.468 mmol) in a mixture of
EtOAc (1.5 mL) and acetonitrile (1.5 mL) was cooled to 0 °C and
treated with a mixture of RuCl3 (0.014 g, 6 mol %) and NaIO4
(0.150 g, 0.703 mmol) in water (0.5 mL). After standing at 0 °C for
15 min, 20% aq Na2S2O3 was added, and the mixture was filtered
using a pad of silica gel and washed several times with EtOAc. Con-
centration of the filtrate rendered a crude oily product that was
purified over a silica flash column using 40:60 hexane–EtOAc as
the eluting solvents, affording 8 as a white hygroscopic solid
H-60), 3.37 (dq, 1H, J6,5/6 ,5 2.0, J6,1/6 ,1 7.6, H-6 or H-60), 1.50 (s,
6H, CH3), 1.40 (s, 6H, CH3); 13C NMR (CDCl3): d 132.2 (C-S (C
arom.)), 131.2 (C-S (C arom.)), 129.6 (C (H-4) or (H-40)), 129.3 (C
arom.), 129.2 (C (H-4) or (H-40)), 125.5 and 124.7 (C arom.),
122.6 (C (H-5) or (H-50)), 121.5 (C (H-5) or (H-50)), 110.4 (C isopro-
pylidene), 110.3 (C isopropylidene), 78.8 (C (H-2) or (H-20)), 77.8 (C
(H-2) or (H-20)), 72.0 (C (H-3) or (H-30)), 71.5 (C (H-3) or (H-30)),
70.1 (C (H-1) or (H-10)), 68.6 (C (H-1) or (H-10)), 65.4 (C (H-6) or
(H-60)), 65.1 (C (H-6) or (H-60)), 28.2 (CH3), 25.8 (CH3). HRESIMS:
m/z calcd for (C15H18O4SNa)+: 317.0818; found: 317.0837.
(0.101 g, 82%). Mp 32–35 °C; ½a D20
ꢀ82 (c 0.63, MeOH); IR (KBr):
ꢁ
3500–3100 (OH, w), 2155 (SCN, s), 1638 (C–O–C, m), 1063 (s);
1H NMR (C3D6O): d 5.05 (d, 1H, J0H,H5 6.0, OH (H-5)), 4.66 (d, 1H,
J0H,H1 6.9, OH (H-1)), 4.63 (d, 1H, J0H,H2 3.8, OH (H-2)), 4.31 (dd,
4.2.2. (1S,2R,3R,6S)-2,3-Isopropylidendioxy-6-(phenylsulfonyl)-
cyclohex-4-ene-1-ol (12)
1H, J3,2 3.1, J3,4 5.4, H-3), 4.27 (dt, 1H, J2,1 3.2, J2,3 3.1, JH2 0H
H-2), 4.14 (dd, 1H, J4,3 5.4, J4,5 5.8, H-4), 3.89 (ddd, 1H, J1,2 3.2, J1,6
9.8, JH1 0H 6.8, H-1), 3.72 (ddd, 1H, JH5 0H 6.0, J5,4 6.1, J5,6 10.6, H-
,
3.1,
Mp 135–137 °C; ½a D26
ꢁ
+13 (c 0.31, CH2Cl2); IR (KBr): 3517 (OH),
1306 and 1146 (sulfone, s); 1H NMR (CDCl3): d 7.89 (dd, 2H, Jo,m 7.2,
Jo,p 1.7, HoSPh), 7.69 (dd, 1H, Jp,m 7.2, Jp,o 1.6, HpSPh), 7.57 (t, 2H, Jm,o
7.5, Jm,p 7.9, HmSPh), 6.05 (dd, 1H, J4,5 10.3, J4,3 3.8, H-4), 5.89 (d, 1H,
J5,4 10.2, H-5), 4.50 (br t, 1H, J3,4 3.8, J3,2 5.6, H-3), 4.09 (t, 1H, J2,1
7.5, J2,3 6.3, H-2), 3.79 (m, 3H, H1, H6 and OH (H-1)), 1.38 (s, 3H,
CH3), 1.33 (s, 3H, CH3); 13C NMR (CDCl3): d 136.1 (C–S (C arom.)),
134.6 (C (HpSPh)), 129.3 (C (HmSPh)), 129.2 (C (HoSPh), 128.7 (C
(H-4)), 122.7 (C (H-5)), 110.5 (C isopropylidene), 77.9 (C (H-2)),
71.3 (C (H-3)), 68.5 and 67.1 (C (H-1) and C (H-6)), 28.1 (CH3),
25.6 (CH3). EIMS: 295 (M+ꢀCH3, 58), 141 (M+ꢀSO2Ph, 21), 125
(M+ꢀSOPh, 27), 77 (Ph, 67); HRESIMS: m/z calcd for (C15H18O5S-
Na)+: 333.0767; found: 333.0778.
,
,
5), 3.32 (t, 1H, J6,1 10.2, J6,5 10.2, H-6), 1.45 (s, 3H, CH3), 1.34 (s,
3H, CH3); 13C NMR (C3D6O): d 110.8 (C isopropylidene), 109.3
(SCN), 80.5 (C (H-4)), 77.4 (C (H-3)), 73.6 (C (H-5)), 70.3 (C (H-
2)), 69.6 (C (H-1)), 55.1 (C (H-6)), 27.9 (CH3), 25.7 (CH3). EIMS:
203 (M+ꢀSCN, 100); HRESIMS: m/z calcd for (C10H15NO5SNa)+:
284.0563; found: 284.0574 and m/z calcd for (C10H15NO5SH)+:
262.0744; found: 262.0756.
4.1.5. (1S,2R,4R,5R)-6-Thiocyanatocyclohexane-1,2,3,4,5-
pentaol (4-deoxy-4-thiocyano-L-chiro-inositol) (9)
To a stirred suspension of 8 (0.095 g, 0.364 mmol) in MeOH–
H2O (3.0 mL–0.5 mL) was added Dowex-50 (H+ form) resin
(0.85 g). After 1 h at rt, the resin was filtered off and washed many
times with MeOH. Concentration by evaporation at reduced pres-
4.3. General procedure for the synthesis of compounds 12 and
13 under RuCl3–NaIO4 (2.0 equiv) conditions
sure gave 9 as a syrup (0.074 g, 93%). ½a D21
ꢁ
ꢀ21 (c 0.50, MeOH);
A solution of 10 (0.042 g, 0.150 mmol) in a mixture of EtOAc
(1.5 mL) and acetonitrile (1.5 mL) was cooled to 0 °C and treated
with a mixture of RuCl3 (7.0 mg, 8 mol %) and NaIO4 (0.067 g,
0.315 mmol) in water (0.5 mL). After 30 min, 20% aq Na2S2O3 was
added, and the mixture was filtered through a pad of silica gel
and washed several times with EtOAc. The solvent was evaporated
to render a crude product that was subjected to flash chromatogra-
phy on silica gel, eluting first with 50:50 hexane–EtOAc to afford
compound 12 (56%) and then with 70:30 EtOAc–hexane to render
dihydroxylated compound 13 (29%) as a white syrup.
IR (KBr): 3600–3200 (OH, w), 2159 (SCN, s), 1074 (s); 1H NMR
(D2O): d 4.09 (br dd, 2H, H-2 and H-3), 3.96 (br dd, 1H, J1,2 3.1,
J1,6 10.9, H-1), 3.76 (q, 2H, J4,3 3.0, J4,5 9.5, J5,4 9.6, J5,6 10.0, H-4
and H-5), 3.23 (t, 1H, J6,1 10.6, J6,5 10.4, H-6); 13C NMR (D2O): d
112.9 (SCN), 72.6 (C (H-4)), 71.9 (C (H-3)), 71.5 (C (H-5)), 70.5 (C
(H-2)), 68.5 (C (H-1)), 55.6 (C (H-6)). HRESIMS: m/z calcd for
(C7H11NO5SNa)+: 244.0250; found: 244.0260 and m/z calcd for
(C7H11NO5SH)+: 222.0431; found: 222.0437.
4.2. General procedure for the synthesis of compounds 11 and
12 under catalytic RuCl3–NaIO4 conditions
4.3.1. (1R,2R,3R,4S,5S,6S)-3,4-Isopropylidendioxy-6-
(phenylsulfonyl)-cyclohexane-1,2,5-triol (13)
A solution of 10 (0.050 g, 0.181 mmol) in a mixture of EtOAc
(1.5 mL) and acetonitrile (1.5 mL) was cooled to 0 °C and treated
with a mixture of RuCl3 (6.0 mg, 6 mol %) and NaIO4 (0.063 g,
0.295 mmol) in water (0.5 mL). After 30 min, 20% aq Na2S2O3 was
added, and the mixture was filtered through a pad of silica gel
and washed several times with EtOAc. The solvent was evaporated
to render a crude oily product that was purified by silica gel flash
½
a 2D0
ꢁ
ꢀ26 (c 1.5, MeOH); IR (KBr): 3500–3100 (OH, w), 1304 and
1144 (sulfone, s); 1H NMR (C3D6O) d 7.97 (br t, 2H, Jo,m 7.2, Jo,p 1.3,
HoSPh), 7.75 (dt, 1H, Jp,m 7.4, Jp,o 1.2, HpSPh), 7.66 (t, 2H, Jm,o 7.1, Jm,p
7.7, HmSPh), 4.71 (d, 1H, J0H,H2 3.8 Hz, OH (H-2)), 4.39 (m, 1H, H-3),
4.35 (dd, 1H, J1,2 5.7, J1,6 7.0, H-1), 4.23 (t, 1H, J6,1 7.4, J6,5 7.4, H-6),
4.14 (t, 1H, J5,6 7.8, J5,4 7.8, H-5), 3.84 (dd, 1H, J2,1 5.5, J2,3 2.3, H-2),
3.41 (dd, 1H, J4,5 7.9, J4,3 3.6, H-4), 1.37 (s, 3H, CH3), 1.28 (S, 3H,

50
A. Bellomo et al. / Carbohydrate Research 344 (2009) 44–51
CH3); 13C NMR (C3D6O): d 139.9 (C-S (C arom.)), 133.7 (C (HpSPh)),
128.9 (di, C (HmSPh)), 128.7 (C (HoSPh), 108.7 (C isopropylidene),
78.2 (C (H-6)), 77.5 (C (H-1)), 71.6 (C (H-2)), 71.4 (C (H-4)), 68.3
(C (H-3)), 68.0 (C (H-5)), 25.2 (CH3), 24.2 (CH3). HRESIMS: m/z calcd
for (C15H20NaO7S)+: 367.0821; found: 367.0815.
4.4.4. (1S,2R, 3S,6S)-4-Bromo-6-(phenylthio)cyclohexene-1,2,3-
triol (18)
A
mixture of compound (1S,2R,3S,6S)-4-bromo-2,3-isopro-
pylidendioxy-6-(phenylthio)cyclohexene-1-ol3,21 (0.036 mg, 0.102
mmol), Dowex-50 (H+ form) resin (0.60 g) and MeOH–H2O
(3.0 mL–0.1 mL) was stirred at room temperature for 24 h. After
completion of the reaction, the resin was filtered off, and the sol-
vent was evaporated under reduced pressure. Purification by flash
chromatography (20:80 hexane–EtOAc) rendered optically active
4.4. Synthesis of some representative compounds evaluated for
biological activity
18 as a white solid (quantitative): mp 114–116 °C; ½a D20
ꢁ
+48 (c
4.4.1. (1S,2S,3S,6S)-4-Bromo-6-thiocyanate-cyclohex-4-en-
1,2,3-triol (15)
1.20, MeOH); IR (KBr): 3500–3400 (OH, w), 2221, 1072, 752; 1H
A mixture of compound 5 (0.022 g, 0.072 mmol), Dowex-50 (H+
form) resin (0.87 g), and MeOH–H2O (2.0–0.2 mL) was stirred at
room temperature for 12 h. After completion of the reaction, the
resin was filtered off, washed with MeOH (3 ꢂ 5 mL), and the sol-
vent was evaporated under reduced pressure. Purification by flash
chromatography (20:80 hexane–EtOAc) rendered optically active
NMR (CD3OD): d 7.53 (dd, 2H, Jo,m 8.5, Jo,p 1.4, HoSPh), 7.33 (dt,
3H, Jp,m 7.1, Jp,o 1.5, Jm, 8.6, Jm,p 7.2, HpSPh and HmSPh), 6.09 (d,
o
1H, J5,5 2.6, H-5), 4.27 (d, 1H, J3,2 4.1, H-3), 3.80 (t, 1H, J1,2 8.4, J1,6
8.4, H-1), 3.69 (dd, 1H, J6,1 9.0, J6-5 2.4, H-6), 3.66 (dd, 1H, J2,1 8.3,
J2,3 4.9, H-2); 13C NMR (CD3OD): d 134.7 (C-S (C arom.)), 132.4 (C
(HoSPh), 132.1 (C (H-5)), 129.4 (C (HmSPh), 127.6 (C (HpSPh)), 123.6
(C–Br), 73.6 (C (H-2)), 73.2 (C (H-3)), 69.5 (C (H-1)), 53.3 (C (H-
6)). EIMS: 282 ((M++2)ꢀ2H2O, 16), 280 (M+ꢀ2H2O, 15), 176 (282-
SPh, 25), 174 (280-SPh, 26), 77 (Ph, 70); Anal. Calcd for
C12H13BrO3S: C, 45.44; H, 4.13. Found: C, 45.33; H, 3.99.
15 as a white solid (96 %): mp 127.2–129.5 °C; ½a D19
ꢁ
+56 (c 0.49,
MeOH); IR (KBr): 3400–3300 (OH, w), 2159 (SCN, s), 1640 (s); 1H
NMR (MeOD): d 6.20 (d, 1H, J5,5 2.8, H-5), 4.29 (d, 1H, J3,2 4.1, H-
3), 3.90 (t, 1H, J1,2 9.6, J1,6 9.6, H-1), 3.72 (dd, 1H, J6,1 10.1, J6-5
2.8, H-6), 3.68 (dd, 1H, J2,1 9.6, J2,3 4.1, H-2); 13C NMR (MeOD): d
128.8 (C (H-5)), 127.3 (C (H-4)), 110.0 (SCN), 73.1 (C (H-3)), 72.8
(C (H-2)), 69.8 (C (H-1)), 53.3 (C (H-6)). EIMS: 98 (M+ꢀBr–OH,
100), 81 (Br, 6), 58 (SCN, 37); Anal. Calcd for C7H8NBrO3S: C,
31.59; H, 3.03; N, 5.26. Found: C, 31.99; H, 3.23; N, 5.15.
4.5. Biological tests
4.5.1. Tests of feeding activity against E. paenulata
Products were evaluated in choice bioassays in Petri dishes
(9 cm x 1 cm) lined at the bottom with a layer of agar (2%). E.
paenulata adults, reared as previously described,23 were offered
four leaf discs (1 cm2) of an appropriate host plant (Cucurbita pepo).
4.4.2. (1R,2S,3S,6R)-4-Bromo-6-thiocyanatocyclohex-4-en-
1,2,3-triol (16)
Two of the discs (T) were coated with 100
of a 1% MeOH solution), and the other two (C) were treated with
10 L of MeOH (5 replicates per product). To measure variability
lg of the product (10 lL
A
stirred solution of (1R,2R,3S,6R)-4-bromo-2,3-isopropyl-
idenedioxy-6-thiocyanato-cyclohex-4-ene-1-ol3,21 (0.051 g, 0.166
mmol) and MeOH–H2O (3.5–0.5 mL) was treated with Dowex-50
(H+ form) resin (0.53 g) for 24 h at rt. The resin was filtered off,
and washed with MeOH (3 ꢂ 5 mL), and the solvent was evapo-
rated under reduced pressure. Purification by flash chromatogra-
phy 30:70 hexane–EtOAc) gave 16 as a white syrup (0.03 g, 79
l
in feeding activity, a visual score of area consumed (0%, 25%, 50%,
75%, or 100%) was assigned for all discs within the plate, every
15 min (total time of the bioassays, 210 min) as described.24 An in-
dex of variability in feeding activity (IFA) was determined for each
plate as IFA = [(control consumption-treatment consumption)/
(control consumption + treatment consumption)] at final time.
Results were analyzed using the Wilcoxon Rank Test.25
%). ½a 1D9
ꢀ78 (c 0.26, MeOH); IR (KBr): 3620–3100 (OH, w), 2159
ꢁ
(SCN, s), 1632 (s); 1H NMR (MeOD): d 6.20 (t, 1H, J5,3 2.2, J5,6 2.2,
H-5), 4.28 (ma, 1H, H-3), 4.17 (dd, 1H, J2,1 5.7, J2,3 3.7, H-2), 3.99
(dt, 1H, J6,1 8.2, J6,5 2.7, J6,3 2.7, H-6), 3.86 (dd, 1H, J1,2 6.3, J1,6 8.2,
H-1); 13C NMR (MeOD): d 130.5 (C 5), 127.4 (C 4), 111.9 (SCN),
72.7 (C 1), 72.3 (C 2), 71.0 (C 3), 51.7 (C 6). EIMS: 183 (M+ꢀBr,
17), 170 (M+ꢀ2H2O–SCN, 17), 81 (Br, 39), 58 (SCN, 59); Anal. Calcd
for C7H8NBrO3S: C, 31.59; H, 3.03; N, 5.26. Found: C, 32.04; H, 3.43;
N, 4.84.
Acknowledgments
The authors are grateful to Mr. Horacio Pezaroglo for recording
NMR spectra and Ms. Natalia Berta and Dr. Alejandra Rodriguez for
performing HRESIMS analysis. A.B. thanks PEDECIBA and ANII for a
Doctoral Fellowship. NMR spectra were processed offline using a
trial version of Mestre Nova generously granted by Mestrelab
Research SRL.
4.4.3. (1S,2R,3R,6S)-6-(Phenylsulfonyl)cyclohex-4-ene-1,2,3-
triol (17)
A mixture of compound 12 (0.021 g, 0.075 mmol), Dowex-50
(H+ form) resin (0.30 g) and MeOH–H2O (2.0 mL–0.2 mL) was stir-
red at room temperature for 48 h. After completion of the reaction,
the resin was filtered off, and washed with MeOH (3 ꢂ 5 mL), and
the solvent was evaporated under reduced pressure. Purification
by flash chromatography (20:80 hexane–EtOAc) rendered optically
Supplementary data
Supplementary data (copies of the 1H NMR and 13C NMR spectra
for all new compounds) associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2008.09.026.
active 17 as a white crystalline solid (95%): mp 76–78 °C; ½a D20
ꢁ
+29
References
(c 0.26, MeOH); IR (KBr): 3500–3300 (OH, w), 1250 and 1020 (sul-
fone, m); 1H NMR (MeOD): d 7.94 (dd, 2H, Jo,m 7.2, Jo,p 1.3, HoSPh),
7.72 (dd, 1H, Jp,m 7.4, Jp,o 1.3, HpSPh), 7.63 (t, 2H, Jm,o 7.7, Jm,p 7.7,
HmSPh), 6.08 (ddd, 1H, J4,5 10.1, J4,3 2.8, H-4), 5.92 (dd, 1H, J5,4 9.9,
J5,6 3.2, H-5), 4.12 (m, 2H, H-3 and H-2), 3.95 (dt, 1H, J1,6 9.8, J1,2
6.7, H1), 3.95 (dd, 1H, J6,1 9.8, J6,5 3.5, H6); 13C NMR (MeOD): d
138.2 (C–S (C arom.)), 133.7 (C (HpSPh)), 132.6 (C (H-4)), 128.9 (C
(HoSPh), 128.7 (C (HmSPh)), 121.0 (C (H-5)), 72.2 (C (H-6)), 69.8 (C
(H-1)), 65.9 and 67.1 (C (H-2) and C (H-3)). HRESIMS: m/z calcd
for (C12H14O5SNa)+: 293.0454; found: 293.0465.
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