Antifungal thiosulfonates: Potency with some selectivity

Article abstract of DOI:10.1071/ch00030

A series of thiosulfonates have been prepared and tested against Aspergillus niger and Aspergillus flavus. In general, the thiosulfonates are moderate antifungal agents - more potent than corresponding inactive disulfides and less potent than corresponding very active fungitoxic disulfides. A pair of thiosulfonates show high selectivity, each killing only one kind of fungus. CSIRO 2000.

Full text of DOI:10.1071/ch00030

C S I R O P U B L I S H I N G
Australian Journal
of Chemistry
Volume 53, 2000
© CSIRO 2000
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Aust. J. Chem., 2000, 53, 399–402
Antifungal Thiosulfonates: Potency with Some Selectivity
Felix Jakob Baerlocher,A,B Mark Otto Baerlocher,A Crystal Lee Chaulk,C
Richard Francis LanglerC,D and Stephanie Lee MacQuarrieC
A Department of Biology, Mount Allison University,
Sackville, New Brunswick, Canada E4L 1G7.
B To whom correspondence should be addressed about the biological testing.
C Department of Chemistry, Mount Allison University,
Sackville, New Brunswick, Canada E4L 1G8.
D To whom correspondence should be addressed about the organic chemistry.
Aseries of thiosulfonates have been prepared and tested against Aspergillus niger and Aspergillus flavus. In general,
the thiosulfonates are moderate antifungal agents—more potent than corresponding inactive disulfides and less
potent than corresponding very active fungitoxic disulfides. A pair of thiosulfonates show high selectivity, each
killing only one kind of fungus.
Keywords. Antifungal; fungitoxins; thiosulfonate synthesis; structure–activity.
Introduction
which would be generally preferred. Scheme 1 presents
results for (i) preparation and peroxide oxidation of methyl
phenyl disulfide, (ii) diphenyl disulfide chlorination, fol-
lowed by nucleophilic substitution with sulfinate anions, and
(iii) benzenethiol chlorination followed by reaction with sul-
finate anions.
In recent papers,1–3 we have described design principles,
and exploited them, to construct potent sulfur-rich antifungal
compounds. The lead structure from which the work began is
the naturally occurring disulfide dysoxysulfone (1).4
Although some disulfides were inactive against test fungi
(Aspergillus niger and Aspergillus flavus), all of our previ-
ously described fungitoxins1–3 are disulfides (see compounds
(2) and (3) in Table 1 for representative structures). In virtually
every case,1–3 a given previously described antifungal disul-
fide showed comparable toxicities for each test fungus.
Inactive non-disulfides included in our screens feature
sulfone, sulfide, mercaptan and sulfonate ester functionalities.
Therefore, this study is focused on structures which retain the
critical SS bond but which have been modified by appending
two oxygen atoms to one of the sulfur atoms (i.e. RSO2SRЈ).
This report addresses the following issues. (i) What are
reliable approaches for routine synthesis of thiosulfonates?
(ii) Are thiosulfonates more potent antifungals than disul-
fides? (iii) Does structural modification of the SS linkage
lead to some selectivity in the killing of fungus?
Scheme 1. Three approaches to phenyl methanethiosulfonate (4)
preparation, with overall yields, from commercially available starting
materials.
Clearly, the best approach would utilize a mercaptan and
a sulfinic acid salt when they are readily available.
Results and Discussion
Although only a few sulfinic acid salts are presently avail-
able commercially, there is well established preparative
methodology for aromatic sulfinic acid salts.6 We have
devised a related approach for the preparation of alkyl
sulfinic acid salts which is applied in Scheme 2 to the prepa-
ration of methyl ethanethiosulfonate (5).
(a) Synthetic Approaches to Thiosulfonates
Established approaches to the preparation of thiosul-
fonates have been reviewed by Field.5 Three of the
approaches he describes have been applied to the preparation
of phenyl methanethiosulfonate (4) in order to determine
Manuscript received 21 February 2000
© CSIRO 2000
10.1071/CH00030
0004-9425/00/050399

400
F. J. Baerlocher et al.
likely to be associated with biochemical sulfenylations
accomplished by these disulfides. Hence, it seemed that thio-
sulfonates, which can effectively sulfenylate mercaptide
anions, might also be effective fungitoxins.
Dimethyl disulfide (10) shows no antifungal behaviour,
while the two closely related thiosulfonates (5) and (11) have
measurable toxicity (see Table 1). Methyl methanethiosul-
fonate (11) is the first compound we have examined which is
effective against only one of the test fungi. Note that the
enhanced toxicity of (5) is not unexpected since, up to a
chain length of nine carbons, longer unbranched alkyl
groups are known to enhance pharmacological effects.7
Scheme 2. Preparation of methyl ethanethiosulfonate (5) with a
sodium alkanesulfinate salt which is not commercially available.
The preparation of p-nitrophenyl methanethiosulfonate
(6) and related thiosulfonates presented a problem. p-
Nitrophenyl disulfide has very low solubility in common
organic solvents which frustrated attempts to react it with
sulfuryl chloride. Furthermore, p-nitrophenyl mercaptan is
not commercially available. Methyl p-nitrophenyl disulfide
(7)3 is a suitable precursor for thiosulfonate (6) preparation
(see Scheme 3).
Table 1. Sulfur compounds as antifungal agents
Each compound was introduced onto a small paper disk which was
placed in a culture medium. The diameter of the clear zone (the area
where fungus—Aspergillus niger or Aspergillus flavus—did not grow)
around each disk indicated antifungal activity
Sulfur
compound
tested
Dose
(ꢀg/
disk)
Diameter (mm) of
clear zone
A. niger
A. flavus
CH3SO2CH2SSCH3 (2)2
CH3SS(C6H4)-o-NO2 (3)3
CH3SSCH3 (10)3
25
10
100
100
50
100
25
25
100
25
25
25
100
10
2.7
2.8
0
3.3
2.0
0
0
1.4
0
3.9
4.3
2.8
0
3.8
1.9
3.0
0
3.8
1.9
0
0
1.3
0
3.7
3.6
0
3.8
3.3
4.3
0
4.0
1.2
2.0
0
CH3SO2SCH3 (11)8
CH3CH2SO2SCH3 (5)9
C6H5SSCH3 (12)3
CH3SO2SC6H5 (4)A
p-CH3(C6H4)SO2SCH3 (13)
C6H5SSC6H5 (14)3
C6H5SO2SC6H5 (15)
p-CH3(C6H4)SO2SC6H5 (16)
CH3SS(C6H4)-o-CO2CH3 (17)3
CH3SO2S(C6H4)-o-CO2CH3 (18)
CH3SS(C6H4)-p-NO2 (7)3
CH3SO2S(C6H4)-p-NO2 (6)
Because each thiosulfonate offers a soft acid site (sulfenyl
sulfur), they are well established sulfenylating agents for
mercaptide anions which are soft bases.5 Unexpectedly, p-
nitrophenyl thiosulfonate serves as a transsulfenylating
agent in a novel approach to thiosulfonate synthesis (see
Scheme 4).
25
p-CH3(C6H4)SO2S(C6H4)-p-NO2 (8) 25
CH3SSCH2CO2CH3 (20)1
100
50
p-CH3(C6H4)SO2SCH2CO2CH3 (9)
2.9
1.7
A
Compound (4) had no measurable fungitoxicity against A. niger at
100 ꢀg/disk.
For the series of compounds (4), (12) and (13), the disul-
fide was inactive and the thiosulfonates antifungal.
Interestingly, the thiosulfonate (4) killed only A. flavus in
contrast to (11) which selectively inhibited the growth of A.
niger.
Compounds (14)–(16) also demonstrate the superior anti-
fungal potency of thiosulfonates relative to simple disulfides
(see Table 1) but, for this set, no selectivity for either of the
fungi was observed.
Compound (17) (Table 1) is the first potent second-gener-
ation antifungal disulfide to be considered here. Perhaps sur-
prisingly, the closely related thiosulfonate (18) is not
antifungal at all. Similar results (diminished fungitoxicity
for the thiosulfonates relative to the disulfide) were obtained
for the set of compounds (6)–(8). It now appears that thio-
sulfonates tend to have moderate fungitoxicity—enhanced
relative to inactive disulfides and diminished relative to
more potent antifungal disulfides. The results in Table 1 open
Since the Scheme 4 reaction appears to involve soft base
attack at a hard acid site, this approach is unlikely to be gen-
erally useful for the preparation of thiosulfonates, unless the
leaving group’s nucleofugality is further enhanced. With
effective access to thiosulfonates in hand, work progressed
to the biological testing phase.
(b) Thiosulfonates as Antifungal Agents
In exploring the development of new, potent antifungal
disulfides,1–3 we have adopted the view that fungitoxicity is

Antifungal Thiosulfonates
401
shield for 0.5 h. Chloroform (100 ml) was added and the resultant
mixture extracted with 2.5% sodium hydroxide solution (three 50-ml
aliquots). The organic layer was dried (MgSO4), filtered and the solvent
evaporated. The crude product was chromatographed on silica gel
(100 g) employing 1: 1 chloroform/light petroleum (100-ml fractions)
for elution. Fractions 11 and 12 were combined and concentrated
affording clean phenyl methanethiosulfonate (4)16 (0.20 g, 1.1 mmol,
17%). Recrystallized (4) (methanol) had m.p. 88.9–90.4°C. I.r. 1335,
1145 cm–1. 1H n.m.r. (270 MHz) ꢃ 3.19, s, 3H; 7.54, m, 3H; 7.72, d, 2H.
13C n.m.r. ꢃ 47.39, 127.93, 129.92, 131.67, 136.24. m/z 188 (35%, M+•),
125 (57), 109 (100).
(B) Benzenesulfenyl chloride from disulfide, then reaction with
methanesulfinate anion. Diphenyl disulfide (1.0 g, 4.6 mmol) was
dissolved in dry methylene chloride (5 ml) and a solution of sulfuryl
chloride (0.6 g, 4.6 mmol) in dry methylene chloride (5 ml) added drop-
wise. Upon completion of the addition, the reaction mixture was
refluxed for 0.5 h. A solution of sodium methanesulfinate (0.94 g, 9.2
mmol) in acetone (40 ml) and water (10 ml) was added to the reaction
mixture which was then immersed in a constant-temperature bath at
50°C for 1 h. The workup described for part (A) furnished diphenyl
disulfide (0.35 g, 35%, from column fractions 2 and 3) and the thiosul-
fonate (4)16 (0.66 g, 3.5 mmol, 38%, from fractions 7–17).
up the possibility that there might be a pharmacological
equivalent to the well known reactivity selectivity principle
in organic chemistry.10 The pharmacological equivalent
might assert that structural modifications which decrease the
potency of a particular agent may be associated with
enhanced selectivity in toxicity within a set of closely related
organisms.
Our interest in antifungal disulfides was encouraged by
the recent observations11–13 that fungal infections frequently
prove to be lethal for immunocompromised patients. Adisul-
fide (19) related to our potent aryl disulfide fungitoxins (e.g.
(7) and (17) in Table 1) has been patented for use in inhibit-
ing the production of Interleukin-1ꢁ and Tumour Necrosis
Factor ꢂ.14 Finally, the ꢂ-ester disulfide (20) (see Table 1)
had no antifungal activity.1 Nonetheless, when tested, it
showed promise as a lead compound in fighting leukaemia.15
The related thiosulfonate (9) shows clearly enhanced anti-
fungal activity but has not yet been assessed as an
antileukaemic agent.
(C) Benzenesulfenyl chloride from mercaptan, then reaction with
methanesulfinate anion. Benzenethiol (1.0g, 9.0 mmol) was reacted
with sulfuryl chloride (1.3 g, 9.7 mmol) and sodium methanesulfinate
(0.96 g, 9.4 mmol) as described for diphenyl disulfide in part (B).
Extractive workup and column chromatography, as described in part
(B), furnished diphenyl disulfide (0.11 g, from fraction 3) and the thio-
sulfonate (4)16 (0.95 g, 5.0 mmol, 55%, from fractions 7–11).
Preparation of S-Methyl Ethanethiosulfonate (5)
(A) Sodium benzenethiolate (2.1 g, 15.6 mmol) was dissolved in
acetone (50 ml) and ethanesulfonyl chloride (1.0 g, 7.8 mmol) added.
The reaction mixture was refluxed for 1 h. Chloroform (200 ml) was
added and the resultant mixture washed with water (100 ml). The
aqueous layer was concentrated and dried in vacuum for 8 h, producing
a mixture (1.12 g) of sodium ethanesulfinate and sodium chloride. The
product had 1H n.m.r. (270 MHz, D2O + (CH3)3Si(CH2)3SO3Na) ꢃ 1.08,
t, 3H; 2.33, q, 2H. 13C n.m.r. ꢃ 7.90, 56.44.
(B) Dimethyl disulfide (0.45 g, 4.8 mmol) was dissolved in dry
methylene chloride (5 ml) and a solution of sulfuryl chloride (0.65 g,
4.8 mmol) in dry methylene chloride (5 ml) added dropwise. Upon
completion of the addition, the reaction mixture was refluxed for 0.5 h.
A solution of the mixture of sodium ethanesulfinate and sodium chlo-
ride (1.12 g) in water (10 ml) and acetone (40 ml) was added. The reac-
tion mixture was immersed in a constant-temperature bath at 50°C for
1 h. Chloroform (200 ml) was added and the resultant mixture extracted
with water (100 ml). The organic layer was dried (MgSO4), filtered and
the solvent evaporated. The crude product was chromatographed on
silica gel (100 g) employing 1: 1 chloroform/light petroleum (30–60°,
100-ml fractions) for elution. Fractions 7–9 were concentrated and
combined affording oily methyl ethanethiosulfonate9 (5) (0.32 g, 2.3
mmol, 29%). I.r. 1325, 1140 cm–1. 1H n.m.r. (270 MHz) ꢃ 1.48, t, 3H;
2.66, s, 3H; 3.34, q, 2H. 13C n.m.r. ꢃ 8.37, 18.21, 55.61. m/z 140 (75%,
M+•), 61 (47), 48 (100).
At this point, potent fungitoxic disulfides show little
selectivity, whereas the selectivity of antifungal thiosul-
fonates is not associated with high potency. We hope that
insight gained in developing more potent antifungal disul-
fides may be applicable to the design of more potent, selec-
tive fungitoxic thiosulfonates.
Experimental
Infrared spectra were recorded on a Perkin–Elmer 710B grating
spectrophotometer for chloroform solutions unless otherwise specified.
1H n.m.r. spectra (60 MHz) were obtained on a Varian EM360L instru-
1
ment. H n.m.r. (270 MHz) and 13C n.m.r. spectra were obtained on a
JEOL JNM-GSX 270 Fourier-transform n.m.r. system. Unless other-
wise specified, all n.m.r. spectra were obtained for (D)chloroform solu-
tions with tetramethylsilane as internal standard. Mass spectra were
obtained on a Hewlett–Packard 5988A g.l.c./m.s. system. Melting
points were determined on a Gallenkamp MFB-595 capillary melting
point apparatus and are uncorrected.
Biological Testing
Details have been provided earlier.1
Preparation of S-p-Nitrophenyl Methanethiosulfonate (6)
Methyl p-nitrophenyl disulfide3 (7) (1.0 g, 5.0 mmol) was dissolved
in dry methylene chloride (5 ml) and a solution of sulfuryl chloride
(0.67 g, 5.0 mmol) in dry methylene chloride (5 ml) added dropwise.
The reaction mixture was refluxed for 0.5 h. A solution of sodium
methanesulfinate (0.5 g, 5.0 mmol) in acetone (40 ml) and water (10 ml)
was added and the reaction mixture immersed in a constant-temperature
bath at 50°C for 1 h. Chloroform (200 ml) was added and the resultant
mixture washed with water (100 ml). The organic layer was dried
(MgSO4), filtered and concentrated. The crude was recrystallized from
methanol (8 ml) and the first crop chromatographed on silica gel (50 g)
employing chloroform (50-ml fractions) for elution. Fraction 4 was
concentrated affording clean p-nitrophenyl methanethiosulfonate (6)
Previously Prepared Compounds (Table 1)
Compound (2) was prepared as described earlier.2 The preparations
of compounds (3), (12), (17) and (7) were outlined previously.3 The
synthesis of compound (20) has been reported.1 Syntheses for com-
pounds (4), (13), (15) and (16) have been described in refs 16, 17, 18
and 19 respectively.
Three Approaches to Synthesis of S-Phenyl Methanethiosulfonate (4)
(A) Disulfide oxidation. Methyl phenyl disulfide3 (1.0 g, 6.4
mmol) and hydrogen peroxide (30%, 1.5 g) were dissolved in glacial
acetic acid (25 ml) and the reaction mixture refluxed behind a safety

402
F. J. Baerlocher et al.
(0.31 g, 1.3 mmol, 26%). Crystalline nitro thiosulfonate (6) consisted of
opaque, pale yellow sheets and had m.p. 98–99°C (Found: C, 36.1; H,
3.0. C7H7NO4S2 requires C, 36.0; H, 3.0%). I.r. 1530, 1440, 1145 cm–1.
1H n.m.r. (270 MHz) ꢃ 3.27, s, 3H; 7.92, d, 2H; 8.33, d, 2H. 13C n.m.r.
ꢃ 48.56, 124.63, 135.40, 136.73, 149.56. m/z 233 (79%, M+•), 170
(100).
petroleum (100-ml fractions) for elution. Fractions 8–18 were com-
bined and concentrated affording thiosulfonate (18) (2.0 g, 8.1 mmol,
68%). After recrystallization from methanol, o-(methoxy-
carbonyl)phenyl methanethiosulfonate (18) consisted of very fine
colourless crystals and had m.p. 37.9–38.4°C (Found: C, 44.4; H, 4.1.
1
C9H10O4S2 requires C, 43.9; H, 4.1%). I.r. 1730, 1335, 1140 cm–1. H
n.m.r. (270 MHz) ꢃ 3.24, s, 3H; 3.95, s, 3H; 7.61, m, 2H; 7.91, m, 2H.
13C n.m.r. ꢃ 48.73, 52.79, 127.54, 130.60, 131.25, 132.35, 135.73,
138.34, 168.83. m/z 167 (100%, M+• –CH3SO2).
Preparation of S-p-Nitrophenyl p-Toluenethiosulfonate (8)
Methyl p-nitrophenyl disulfide (7)3 (2.5 g, 12.4 mmol) was con-
verted into p-nitrophenyl p-toluenethiosulfonate (8) by using the
procedure (replace sodium methanesulfinate with sodium p-toluenesul-
finate) outlined above for the preparation of (6). Crude product was not
recrystallized but was chromatographed on silica gel (150 g) employ-
ing 1 : 1 chloroform/light petroleum (30–60°, 100-ml fractions) for
elution. Fractions 3–10 were combined and concentrated and the
product was recrystallized (methanol). Recrystallized (8) was sublimed
(110°C/2 Torr/12 h) affording p-nitrophenyl p-toluenethiosulfonate (8)
(1.4 g, 4.6 mmol, 37%). Crystalline thiosulfonate (8) consisted of pale
yellow clumps and had m.p. 135–137°C (Found: C, 49.6; H, 3.4.
C13H11NO4S2 requires C, 50.5; H, 3.6%). I.r. 1525, 1345, 1145 cm–1. 1H
n.m.r. (270 MHz) ꢃ 2.44, s, 3H; 7.25, d, J 8.1 Hz, 2H; 7.50, d, J 8.1 Hz,
2H; 7.60, d, 2H; 8.18, d, J 8.1 Hz, 2H. 13C n.m.r. ꢃ 21.73, 124.15,
127.57, 129.76, 135.77, 137.10, 140.17, 145.60, 149.38.
Acknowledgments
The authors acknowledge financial support from Mount
Allison University. High-field n.m.r. spectra were obtained
by D. Durant and mass spectra by R. Smith. Mass spectral
data for (9) were kindly provided by Dr J. S. Grossert.
References
1
Baerlocher, F. J., Langler, R. F., Frederiksen, M. U., Georges, N. M.,
and Witherell, R. D., Aust. J. Chem., 1999, 52, 167.
Langler, R. F., MacQuarrie, S. L., McNamara, R. A., and O’Connor,
2
P. E., Aust. J. Chem., 1999, 52, 1119.
Baerlocher, F. J., Baerlocher, M. O., Langler, R. F., MacQuarrie, S.
3
L., and Marchand, M. E., Aust. J. Chem., 2000, 53, 1.
Block, E., DeOrazio, R., and Thiruvazhi, M., J. Org. Chem., 1994,
Preparation of Methyl 2-(p-Tolylsulfonylthio)acetate (9)
4
A solution of p-nitrophenyl p-toluenethiosulfonate (8) (1.0 g, 3.2
mmol) in dimethyl sulfoxide (5 ml) was added to a solution of the
sodium salt of methyl thioglycolate (0.4 g, 3.2 mmol) in dimethyl sul-
foxide (5 ml) and the reaction mixture stirred at ambient temperature
for 2.5 h. Hydrochloric acid (2.5%, 200 ml) was added and the resultant
mixture extracted with diethyl ether (three 100-ml aliquots). The
organic layers were combined and concentrated and the extractive pro-
cedure was repeated. The combined organic layers were dried
(MgSO4), filtered and the solvent was evaporated. Crude product was
chromatographed on silica gel (100 g) employing chloroform (100-ml
fractions) for elution. Fractions 6 and 7 were combined and concen-
59, 2273.
5
Field, L., in ‘Organic Chemistry of Sulfur’ (Ed. S. Oae) pp. 321,
348–351 (Plenum: New York 1977).
Bere, C. M., and Smiles, S., J. Chem. Soc., 1924, 125, 2361.
Silverman, R. B., ‘The Organic Chemistry of Drug Design and Drug
Action’ p. 16 (Academic: San Diego 1992).
Freeman, F., and Keindl, M. C., J. Org. Chem., 1988, 53, 2026.
Block, E., Bentley, M. D., Davis, F. A., Douglass, I. B., and Lacadie,
J. A., J. Org. Chem., 1975, 40, 2770.
Lowry, T. H., and Richarson, K. S., ‘Mechanism and Theory in
Organic Chemistry’ 3rd Edn, p. 148 (Harper & Row: New York
1987).
Pfaller, M., and Wenzell, R., Eur. J. Clin. Microbiol. Infect. Dis.,
1992, 11, 287.
Debono, M., and Gordee, R. S., Annu. Rev. Microbiol., 1994, 48,
471.
Sternberg, S., Science, 1994, 266, 1632.
Katsuyama, K., Ariga, M., Saito, Y., Hatanaka, S., and Takahashi,
6
7
8
9
10
1
trated, yielding oily thiosulfonate (9). I.r. 1745, 1320, 1150 cm –1. H
11
n.m.r. (270 MHz) ꢃ 2.47, s, 3H; 3.72, s, 3H; 4.11, s, 2H; 7.38, d, 2H;
7.82, d, 2H. 13C n.m.r. ꢃ 21.73, 53.08, 60.93, 128.54, 129.90, 135.71,
145.52, 162.99. m/z 228 (M+• – S, 24%) (Found: 228.0456. C10H12O4S
requires 228.0454), 155 (37), 105 (23), 91 (100).
12
13
Preparation of Methyl o-(Methylsulfonylthio)benzoate (18)
14
Methyl o-mercaptobenzoate3 (2.0 g, 11.9 mmol) was dissolved in
dry methylene chloride (5 ml) and a solution of sulfuryl chloride (1.6 g,
11.9 mmol) in dry methylene chloride (5 ml) added dropwise. The reac-
tion mixture was refluxed for 0.5 h. A solution of sodium methanesul-
finate (1.2 g, 11.9 mmol) in acetone (40 ml) and water (10 ml) was
added to the reaction mixture which was immersed in a constant-tem-
perature bath at 50°C for 1 h. Chloroform (200 ml) was added and the
resultant mixture washed with water (100 ml). The organic layer was
dried (MgSO4), filtered and the solvent evaporated. Crude product was
chromatographed on silica gel (100 g) employing 1: 1 chloroform/light
T., U.S. Pat. 5,698,564 (1997).
Wong, W. W. L., MacDonald, S., Langler, R. F., and Penn, L. Z.,
Anticancer Res., in press.
Oae, S., Takata, T., and Kim, Y. H., Bull. Chem. Soc. Jpn, 1982, 55,
15
16
2484.
17
Goodridge, R. J., Hambley, T. W., and Haynes, R. K., J. Org. Chem.,
1988, 53, 2881.
Langler, R. F., Ryan, D. A., and Verma, S. D., Sulfur Lett., in press.
Back, T. G., Collins, S., and Krishna, M. V., Can. J. Chem., 1987,
18
19
65, 38.