Rhodanine derivatives as potent anti-HIV and anti-HSV microbicides
mixture was stirred until the two layers became clear. The aqueous layer was extracted three
times with EtOAc, then the organic phase were washed several times with H2O and brine,
dried over Na2SO4, filtered and evaporated under reduced pressure. The crude product was
purified by flash chromatography using PE/EtOAc = 4:1 as eluent to yield the wishes product
5 as a light orange solid (yield: 96%); mp = 150˚C (decomposition); 1H NMR (CDCl3, 400
MHz): ð = 10.84 (s, 1H), 9.69 (s, 1H), 7.91–7.88 (d, 1H, J = 12 Hz), 7.40–7.39 (d, 1H, J = 4 Hz),
7.35–7.32 (m, 3H), 6.94–6.93 (d, 1H, J = 4Hz), 3.97 (s, 3H); 13C (CDCl3, 100 MHz): ð = 177.47,
161.69, 157.37, 152.53, 135.17, 130.58,122.56, 115.74, 113.73, 112.82, 109.84, 52.40, 29.59; MS
(ES): m/z 245.0 [M-H]-; Anal. (C13H10O5) C, H, N.
4-(5-Formylfuran-2-yl)-2-hydroxybenzoic acid (6). Compound 5 was dissolved in 25
mL of CH3OH, then a solution of NaOH 1M (5.00 mmol) was added dropwise, after the reac-
tion mixture was heated at reflux. The reaction mixture was stirred overnight until completion
(TLC). Organic solvent was removed under reduced pressure, then some water was added,
and the aqueous layer was extracted three times with Et2O; the aqueous layer was then acidi-
fied to pH 1 with HCl 6N and a precipitated appeared. (6) was obtained as a brown-red solid
(yield: 95%); mp = 230˚C (decomposition); 1H NMR (DMSO, 400 MHz): ð = 9.63 (s, 1H),
7.88–7.86 (d, 1H, J = 8 Hz), 7.66–7.65 (d, 1H, J = 4 Hz), 7.45–7.39 (m, 3H); 13C NMR (DMSO,
100 MHz): ð = 178.72, 171.68, 161.69, 156.82, 152.63, 135.11, 131.72, 125.14, 116.02, 114.06,
113.29, 111.53; MS (ES): m/z 231.0 [M-H].
General Procedure for the synthesis of final compounds 9a-f. To a solution of bis(car-
boxymethyl)trithiocarbonate (0.22 mmol) in DME (1.0 mL) were added TEA (0.22 mmol) and
the opportune amine (0.22 mmol). The reaction mixture was heated at 90˚C for 10 min under
microwave irradiation. After this time, the aldehyde 6 (0.22 mmol) was added, and the mixture
was heated at 110˚C for 5 min under microwave irradiation. The reaction mixture was evapo-
rated to dryness and the residue was additioned with MeOH and a drop of HCl 2N; the final
rhodanine derivatives were obtained as a pure precipitate, isolated by filtration, washed with
water and hexane, and finally dried under high vacuum.
(Z)-4-(5-((3-(4-fluorophenethyl)-4-oxo-2-thioxothiazolidin-5-ylidene)methyl)furan-
2-yl)-2-hydroxybenzoic acid (9a). (yield: 30%); Yellow solid. Mp = 292˚C (decomposition),
1H NMR: (400 MHz, DMSO-d6) d = 7.92–7.90 (d, 1H, J = 8.0 Hz), 7.61 (s, 1H), 7.42–7.41 (d,
1H, J = 3.2 Hz), 7.38–7.33 (m, 3H),7.26–7.22 (m, 2H), 7.11–7.06 (m, 2H), 4.26.4.22 (m, 2H),
2.99–2.95 (m, 2H) ppm. 13C NMR (100 MHz, DMSO-d6): d = 194.20, 171.72,166.65, 161.84,
156.71, 154.49, 150.43, 134.83, 134.20, 131.78, 131.00,130.91, 123.19, 119.91, 118.46, 116.16,
115.72, 115.51, 113.76, 113.04,112.41, 45.63, 31.68 ppm. MS (ES): m/z 468.0 [M-H]-. HPLC:
tr = 4.58 min; conditions: temp = 25˚C, mobile phase composed of (A)70% acetonitrile and
(B) 30% water with 0.5% formic acid at a flowrate of 1.0 mL/min; purity: 96.5%.
(Z)-2-hydroxy-4-(5-((3-(4-methylphenethyl)-4-oxo-2-thioxothiazolidin-5-ylidene)
methyl)furan-2-yl)benzoic acid (9b). (yield: 79%); Orange solid. Mp = 258˚C (decomposi-
tion);1H NMR: (400 MHz DMSO-d6) d = 7.91–7.89 (d, 1H, J = 8.0 Hz), 7.60 (s, 1H), 7.42–7.33
(m, 4H), 7.10–7.08 (m, 4H), 4.21–4.18 (m, 2H), 2.92–2.88 (m, 2H), 2.25 (s, 3H) ppm. 13C
NMR (100 MHz, DMSO-d6): d = 194.03, 178.56, 171.56, 166.68, 161.84, 156.79, 150.52, 135.99,
134.93, 131.77, 129.44, 128.88, 122.95, 120.15, 118.36, 115.56, 114.37, 113.86, 112.91, 112.52,
11.32, 45.70, 32.16, 20.96 ppm. MS (ES): m/z 464.0 [M-H]-. HPLC: tr = 4.65 min; conditions:
temp = 25˚C, mobile phase composed of (A) 70% acetonitrile and (B) 30% water with 0.5%
formic acid at a flow rate of 1.0 mL/min; purity:95.9%.
(Z)-2-hydroxy-4-(5-((4-oxo-3-(3-phenylpropyl)-2-thioxothiazolidin-5-ylidene)methyl)
furan-2-yl)benzoic acid (9c). (yield: 91%); Orange solid. Mp = 248˚C (decomposition);
1HNMR: (400 MHz, DMSO-d6) d = 7.90–7.88 (d, 1H, J = 8.4 Hz), 7.61 (s,1H), 7.44–7.43 (d,
1H, J = 4.0 Hz), 7.36–7.32 (m, 2H), 7.28–7.14 (m, 5H), 4.04–4.01 (m, 2H), 2.66–2.62 (m, 2H),
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