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dried over magnesium sulfate. Evaporation leaves a crude syrup,
which is taken up in diethyl ether and extracted with 4 N hydro-
genchloride solution. Evaporation of the organic phase gives 2.1 g
(50%) of the amide 8b as a colourless syrupy mass.
4.5.8. Compound 9d. The lactone 7 (1.00 g, 5.5 mmol) is directly
incubated according 6a in buffer/acetone (20 ml:4 ml). The result-
ing orange solid is filtered off, washed with water and lyophilized
from dioxane to yield 0.32 g (32%) of benzotropolone 9d.
1H NMR (CDCl3): 0.80 (3H, t, J¼6.9 Hz), 1.13–1.23 (10H, m), 1.35
(2H, quint., J¼7.2 Hz), 2.44 (2H, t, J¼8.4 Hz), 2.73 (2H, t, J¼8.4 Hz),
3.42 (2H, q, J¼7.6 Hz), 5.70 (NH, t, J¼7.0), 6.39 (2H, s). 13C NMR
(DMSO-d6): 14.1, 22.6, 24.3, 26.8, 29.1, 29.2, 29.3, 31.8, 37.4, 40.1,
107.6, 120.3, 120.4, 133.2, 142.5, 142.9, 174.8.
1H NMR (DMSO-d6): 2.36 (2H, t, J¼6.3 Hz), 2.55 (2H, t, J¼6.3 Hz),
2.93 (2H, t, J¼6.0 Hz), 3.17 (2H, t, J¼6.0 Hz), 3.38 (2OH), 6.90 (1H, d,
J¼12.1 Hz), 7.56 (1H, d, J¼12.1 Hz), 9.61 (OH), 9.81 (OH), 10.22 (OH).
13C NMR (DMSO-d6): 21.5, 29.6, 32.6, 33.7, 115.3, 117.1, 127.3, 127.9,
129.7, 129.8, 134.1, 149.8, 149.9, 152.0, 173.7, 173.8, 181.3. ESI-HRMS
m/z 363.07203 [MꢂH]ꢂ (calcd for C17H15O9: 363.07216).
4.5.4. Compound 8c. Commercial food additive taurin (3.27 g,
26.2 mmol) is dissolved at room temperature in dioxan/water
(25 ml:12.5 ml) and 6.53 ml of 4 N sodiumhydroxide solution.
Lactone 7 (5.0 g, 26.6 mmol) is then added portionwise to this
mixture at 0 ꢀC and stirred for 1 h. The mixture is then lyophilized
and the resulting white powder extensively washed with acetone.
The taurin sodium salt adduct 8c is obtained as a very hygroscopic
material in 98% yield (8.4 g) after a final lyophilization from water.
1H NMR (D2O): 1.90 (3H, t, J¼6.6 Hz), 2.20 (2H, t, J¼6.6), 2.41
(2H, t, J¼6.9 Hz), 2.93 (2H, t, J¼6.9 Hz), 5.89 (2H, 2ꢁs). 13C NMR
(DMSO-d6): 25.4, 35.2, 36.6, 52.4, 106.8, 118.1, 118.4, 133.9, 141.9,
143.4, 172.7.
4.5.9. Compound 9e. According to the above protocol for 6a, com-
pound 9e is obtained from pyrogallol derivative 8e (0.56 g,
1.5 mmol). After incubation for 2 d in buffer a sticky orange residue
is filtered off, washed with water and lyophilized from dioxane to
give 0.30 g (57%) of benzotropolone glucamide 9b.
1H NMR (DMSO-d6): 2.30 (2H, t, J¼6.0 Hz), 2.42 (2H, t, J¼6.0 Hz),
2.92 (2H, t, J¼6.0 Hz), 3.06 (2H, m), 3.27 (2H, t, J¼6.0 Hz), 3.36–3.75
(28H, m), 6.86 (1H, d, J¼9.3 Hz), 7.57 (1H, d, J¼9.3 Hz), 7.84 (1H, br t,
NH), 7.93 (1H, br t, NH). 13C NMR (DMSO-d6): 22.2, 29.8, 34.4, 35.3,
42.0, 42.1, 63.3, 69.5, 71.4, 71.7, 72.0, 115.2, 117.7, 127.2, 127.5, 129.7,
130.6, 134.3, 149.6, 149.9, 151.8, 171.6, 172.1, 181.2. ESI-HRMS m/z
689.24027 [MꢂH]ꢂ (calcd for C29H41O17N2: 689.23997).
4.5.5. Compound 8e. The lactone 7 (2.20 g, 12 mmol) is added to
a solution of glucamine (2.20 g, 12 mmol) in 15 ml of dime-
thylformamide at room temperature and stirred for 24 h. The clear
orange solution is then dropped into 100 ml of dichloromethane
and the resulting precipitate recovered by centrifugation and
washed subsequently with dichloromethane and diethyl ether. The
glucamine adduct 8e is obtained in 98% (4.20 g).
4.5.10. Compound 10. In an argon atmosphere lithium aluminium
hydride (0.59 g, 15.5 mmol) suspended in 5 ml of dry tetrahydro-
furan containing benzyl bromide (2.60 g, 15.2 mmol) is stirred for
15 min at room temperature. Thereafter the flask is cooled to 0 ꢀC
and lactone 7 (1.00 g, 5.6 mmol) dissolved in 10 ml tetrahydrofuran
is dropped in slowly whereby a white precipitate forms. After 0.5 h
the mixture is quenched by successively adding 2 N hydro-
genchloride solution and ethylacetate. The organic phase is then
separated and extracted with water, hydrogenchloride solution and
dried over magnesium sulfate. Evaporation of the solvent leaves
0.80 g (78%) of compound 10 as an oily residue, which is used as
obtained.
1H NMR (D2O): 2.542 (2H, t, J¼7.2 Hz), 2.82 (2H, t, J¼7.92 Hz),
3.16 (1H, dd, J¼7.5 Hz,13.8 Hz), 3.36 (1H, dd, J¼4.5 Hz,13.8 Hz), 3.62
(3H, m), 3.72 (3H, m), 6.46 (1H, d, J¼8.4 Hz), 6.58 (1H, d, J¼8.4 Hz).
13C NMR (D2O): 25.5, 36.6, 47.7, 62.6, 70.0, 71.0, 71.1, 71.4, 107.9,
120.2, 120.8, 132.8, 143.4, 143.8, 176.3.
4.5.6. Compound 9a. According to the above protocol for 6a,
compound 9a is obtained from pyrogallol derivative 8a (1.00 g,
3.3 mmol). After incubation for 24 h in buffer/acetone
(20 ml:10 ml) the resulting residue is filtered off, washed with
water and lyophilized from dioxane to give 9a as an orange solid in
30% (0.28 g) yield.
1H NMR (DMSO-d6): 1.62 (2H, quint., J¼6.0 Hz), 2.43 (2H, t,
J¼6.0 Hz), 3.39 (OH and 2H, t, J¼6.0 Hz), 6.20 (1H, d, J¼6.3 Hz), 6.32
(1H, d, J¼6.3 Hz), 8.02 (OH), 8.12 (OH), 8.74 (OH). 13C NMR (DMSO-
d6): 25.9, 33.1, 59.7, 106.2, 118.9, 119.6, 132.8, 143.9, 144.1, 170.8.
4.5.11. Compound 11. According to the above protocol for 6a, com-
pound 11 is obtained from pyrogallol derivative 10 (0.70 g,
3.8 mmol). After incubation for 24 h in buffer/acetone (20 ml:25 ml)
an orange residue is filtered off, washed with water and lyophilized
from dioxane to give 0.36 g (56%) of benzotropolone 11.
1H NMR (CD3OD): 1.58 (4H, 2ꢁt, J¼7.6 Hz), 2.18 (4H, 2ꢁt,
J¼7.6 Hz), 2.43 (2H, t, J¼6.6 Hz), 2.55 (2H, t, J¼6.6 Hz), 2.92 (2H, t,
J¼7.8 Hz), 3.13 (4H, m), 3.21 (2H, t, J¼7.8 Hz), 6.65 (1H, d,
J¼12.1 Hz), 7.44 (1H, d, J¼12.1 Hz), 7.85 (2H, br, NH). 13C NMR
(CD3OD): 14.4, 25.6, 32.0, 36.4, 31.6, 37.2, 39.7, 52.1, 117.0, 119.1,
128.8, 129.1, 131.9, 132.3, 136.0, 150.9, 151.1, 153.6, 173.8, 174.0,
174.2, 174.5, 182.8. ESI-HRMS m/z 585.35442 [MꢂH]ꢂ (calcd for
C33H49O5N2: 585.35453).
1H NMR (CD3OD): 1.68 (2H, quint., J¼6.0 Hz), 1.77 (2H, quint.,
J¼6.0 Hz), 2.71 (2H, t, J¼6.0 Hz), 2.94 (2H, t, J¼6.0 Hz), 3.51 (4H, t,
J¼6.0 Hz), 6.66 (1H, d, J¼12.3 Hz), 7.49 (1H, d, J¼12.3 Hz). 13C NMR
(CD3OD): 23.2, 31.8, 33.0, 33.7, 62.7, 62.8, 117.0, 119.8, 129.0, 129.1,
131.8, 132.3, 135.3, 150.6, 150.8, 153.3, 182.9. ESI-HRMS m/z
335.11329 [MꢂH]ꢂ (calcd for C17H19O7: 335.11363).
4.5.7. Compound 9b. According to the above protocol for 6a,
compound 9b is obtained from pyrogallol derivative 8b (1.00 g,
3.2 mmol). After incubation for 24 h in buffer/acetone
(25 ml:25 ml) a sticky orange residue is filtered off, washed with
water and lyophilized from dioxane. The resulting residue is
chromatographed over silica gel (eluent: dichloromethane/meth-
anol 10:1) to give 0.81 g (45%) of amide 9b.
Acknowledgements
The authors gratefully acknowledge some preparative assis-
tance for high pressure hydrogenations and reaction optimizations
by the Labs of Dr. K. Friztsche und A. Schneider.
1H NMR (CD3OD): 0.80 (6H, t, J¼6.9 Hz), 1.10–1.25 (20H, m), 1.35
(4H, quint., J¼7.2 Hz), 2.23 (2H, t, J¼7.5 Hz), 2.45 (2H, t, J¼7.5 Hz),
2.93 (2H, t, J¼7.5 Hz), 3.04 (4H, t, J¼7.6 Hz), 3.19 (2H, t, J¼7.6), 6.78
(1H, d, J¼12.6 Hz), 7.50 (1H, d, J¼12.6 Hz). 13C NMR (DMSO-d6): 14.1,
23.7, 27.0, 27.2, 30.4, 30.5, 31.9, 36.0, 37.0, 37.9, 40.6, 117.1, 118.7,
128.9, 129.1, 130.8, 132.0, 136.1, 151.0, 151.1, 153.6, 174.9, 175.4, 182.9.
ESI-HRMS m/z 585.35442 [MꢂH]ꢂ (calcd for C33H49O5N2:
585.35453).
References and notes
1. Haslam, E. Phytochemistry 2003, 64, 61–73.
2. Sang, S.; Tian, S.; Meng, X.; Stark, R. E.; Rosen, R. T.; Yang, C. S.; Ho, C.-T.
Tetrahedron Lett. 2002, 43, 7129–7133.
3. Matsuo, Y.; Tanaka, T.; Kuono, I. Tetrahedron 2006, 62, 4774–4783.
4. Ho, C. -T.; Ghai, G.; Sang S.; Jhoo, J. -W.; Huang, M. -T.; Rosen, T. R.; Dushenkov,
S. U.S. Patent 0,049,284, 2005.