3886
A. Pezzella et al. / Tetrahedron Letters 48 (2007) 3883–3886
+
(
(
C), 112.9 (CH), 126.0 (C), 134.2 (CH), 138.2 (C), 139.6
C), 170.7, 171.0 (2 · OCOCH ). Compound 2b: ESI(+)-
HRMS calculated for C16
H
16NO
7
S 366.0647 [M+H] ,
1
3
found 366.0700; UV kmax (MeOH) 304 nm; H NMR
(CD OD) d (ppm): 2.28 (6H, s, OCOCH ), 2.40 (3H, s,
+
MS m/z = 349 [M+H] ; ESI-HRMS calculated for
C
3
3
+
15
H
13
N
2
O
6
S 349.0494 [M+H] , found 349.0506; UV
SCOCH
3
), 3.90 (3H, s, COOMe) 7.33 (1H, s), 7.34 (1H, s);
1
13
k
max (MeOH) 304 nm; H NMR (CD
3H, s, OCOCH ), 2.31 (3H, s, OCOCH
COOMe), 7.40 (1H, s, H-7), 7.68 (1H, s, H-4); C NMR
3
OD) d (ppm): 2.30
C NMR (CD
), 53.47 (COOCH
(CH), 129.2 (C), 132.16 (C), 135.6 (C), 140.4 (C), 143.7
(C), 162.9 (COOMe), 171.2, 171.6 (2 · OCOCH ), 196.4
(SCOCH ). Compound 3c: ESI(+)-MS m/z = 250
3
OD) d (ppm): 21.4 (2 · OCOCH
3
), 30.6
(
3
3
), 4.01 (3H, s,
(SCOCH
3
3
), 97.5 (C), 109.0 (CH), 115.6
1
3
(
(
(
(
CD
3
3
OD) d (ppm) 21.0 (2 · OCOCH ), 53.9 (OCH
3
), 96.3
3
C), 109.1 (CH), 112.2 (C), 114.7 (CH), 126.5 (C), 127.3
C), 135.2 (C) 140.3 (C), 143.5 (C), 163.0 (C), 170.6
OCOCH
3
+
[M+H] ; ESI-HRMS calculated for C H NO S
12
12
3
+
3
), 171.0 (OCOCH
3
). Compound 2c: ESI(+)-MS
250.0538 [M+H] , found 250.0590. UV kmax (MeOH)
+
1
m/z = 233 [M+H] ; ESI-HRMS calculated for
C
(
2
285 nm
2.31(3H · 2, s, COCH
7.40 (1H, d, J = 1.8 Hz), 7.47 (1H, d, J = 8.2 Hz), 7.54
H
NMR (400 MHz, CD
3
OD)
d
(ppm):
+
11
H
9
2
N O
2
S 233.0385 [M+H] , found 233.0390. UV kmax
3
), 7.00 (1H, dd, J = 8.2, 1.8 Hz),
1
MeOH) 274 nm; H NMR (400 MHz, CD OD) d (ppm):
3
1
3
.31 (3H, s, OCOCH
3
), 7.01 (1H, dd, J = 8.6, 2.2 Hz), 7.41
(1H, s); C NMR (100 MHz, CD
3
OD) d (ppm):. 21.8
(
1H, dd, J = 2.2, 0.6 Hz), 7.48 (1H, dd, J = 8.6, 0.6 Hz),
(OCOCH ), 31.6 (SCOCH ), 98.2 (C), 112.2 (CH), 115.0
(CH), 119.7 (CH) , 130.1 (C), 134.9 (C), 135.6 (CH) , 148.3
3
3
1
3
7
2
1
1
.76 (1H, br s); C NMR (100 MHz, CD
3
OD) d (ppm):
1.9 (–OCOCH ), 92.8 (C), 98.8 (C), 112.2 (CH), 113.7 (C),
(C), 172.9 (OCOCH ), 196.4 (SCOCH ). Compound 3d:
3
3
3
+
15.0 (CH), 119.7 (CH), 131.2 (C), 135.6 (CH), 148.0 (C),
ESI(+)-MS m/z = 308 [M+H] ; ESI-HRMS calculated
+
for C14H14NO S 308.0593 [M+H] , found 308.0620; UV
kmax (MeOH) 299 nm; H NMR ((CD ) CO) d (ppm):
72.9
(OCOCH
3
).
Compound
2d:
ESI(+)-MS
5
+
1
m/z = 291 [M+H] ; ESI-HRMS calculated for
C H N O S 291.0439 [M+H] , found 291.0390; UV
k
3 2
+
2.29 (3H, s, OCOCH ), 2.44 (3H, s, SCOCH ), 3.92 (3H, s,
13
11
2
4
3
3
1
max (MeOH) 300 nm; H NMR (400 MHz, CD
3
OD) d
COOMe), 7.25 (1H, dd, J = 8.8, 2.4 Hz), 7.31 (1H, d,
13
(
ppm): 2.31 (3H, s), 4.00 (3H, s), 7.14 (1H, dd, J = 9.0,
J = 2.4 Hz), 7.67 (1H, d, J = 8.8 Hz);
C NMR
2
.2 Hz), 7.51 (1H, d, J = 9.0 Hz), 7.54 (1H, d, J = 2.2 Hz);
((CD ) CO) d (ppm): 20.9 (OCOCH ), 30.3 (SCOCH
3
2
3
3
1
3
C NMR (100 MHz, CD
4.2 (OCH ), 97.2 (C), 114.0 (CH), 115.0 (C), 116.4 (CH),
23.7 (CH), 126.9 (C), 130.7 (C), 135.7 (C), 148.9 (C), 162.4
3
OD) d (ppm): 23.2 (COCH
3
),
shoulder of the solvent signal), 52.3 (COOCH
3
), 95.9 (C),
5
1
3
113.1 (CH), 114.4 (CH), 121.6 (CH), 130.7 (C), 131.1 (C),
134.7 (C), 146.8 (C), 160.8 (COOMe), 170.1 (OCOCH ),
3
(
OCOCH ), 173.0 (OCOCH ) Purity (>95%) of all prod-
192.3 (SCOCH ). Purity (>95%) of all products obtained
3
3
3
1
1
ucts obtained in Table 1 was demonstrated by H NMR.
2. Schlosser, K. M.; Krasutsky, A. P.; Hamilton, H. W.;
in Table 1 was demonstrated by H NMR.
1
1
1
16. Thiocyanation of the free acid (1b; R = CO
2
H) resulted
Reed, J. E.; Sexton, K. Org. Lett. 2004, 6, 819–821.
3. (a) Richter, R.; Ulrich, H. In The Chemistry of Cyanates
and Their Thio Derivatives, Part 2; Patai, S., Ed.; Wiley:
Chichester, 1977; pp 619–818; (b) Guy, R. G. In The
Chemistry of Cyanates and their Thio Derivatives, Part 2;
Patai, S., Ed.; Wiley: Chichester, 1977; pp 819–886.
4. (a) Toste, F. D.; LaRonde, F.; Still, I. W. J. Tetrahedron
Lett. 1995, 36, 2949–2952; (b) Zhan, Z.-P.; Lang, K.; Liu,
F.; Hu, L.-M. Synth. Commun. 2004, 34, 3203–3208; (c)
Still, I. W. J.; Toste, F. D. J. Org. Chem. 1996, 61, 7677–
in a quite complex mixture in which the main product was
2-carboxy-5,6-dihydroxy-3-thiocyanoindole (probably the
deacetylation occurred because of the methanol in the acid
medium due to the oxone). Moreover, in the next step, the
work up of the reduction mixture also suffered of serious
yield decrease probably because of the formation of
samarium-carboxyindole complexes difficult to destroy
1
1
5
even by treating with a tartrate solution.
17. Still, I. W. J.; Sayeed, V. A. Synth. Commun. 1983, 13,
1181–1192.
7
680.
18. 5,6-Dihydroxy-3-mercaptoindole,
amorphous
solid,
À
1
5. Reduction of thiocyanates 2a–d was carried out as follows
ESI(À)-MS = m/z 180 (MÀH) ; UV kmax (MeOH) 280
(sh), 300 nm; NMR: see Table 3. 2-Carbomethoxy-5,6-
dihydroxy-3-mercaptoindole, amorphous solid, ESI(À)-
(
(
see also Table 2). A 0.1 M SmI2 solution in dry THF
2.5 equiv) was added to a solution of the appropriate
À
thiocyanate in the same solvent at rt under an argon
atmosphere. After few minutes the colour of the mixture
turned from blue to yellow and the progress of the
reaction was monitored by TLC analysis. When necessary
MS = m/z 238 (MÀH) , UV kmax (MeOH) 310, 340 (sh)
nm.
19. Hirota, M.; Hoshi, R. Tetrahedron 1969, 25, 5953–5960.
20. Silvestri, R.; Artico, M.; Bruno, B.; Massa, S.; Novellino,
E.; Greco, G.; Marongiu, M. E.; Pani, A.; De Montis, A.;
La Colla, P. Antiviral Chem. Chemother. 1998, 9, 139–148.
21. Unangst, P. C.; Connor, D. T.; Stabler, S. R.; Weikert, R.
J.; Carethers, M. E.; Kennedy, J. A.; Thueson, D. O.;
Chestnut, J. C.; Adolphson, R. L.; Conroy, M. C. J. Med.
Chem. 1989, 32, 1360–1366.
22. Zelesko, M. J.; McComsey, D. F.; Hageman, W. E.;
Nortey, S. O.; Baker, C. A.; Maryanoff, B. E. J. Med.
Chem. 1983, 26, 230–237.
23. De Martino, G.; Edler, M. C.; La Regina, G.; Coluccia,
A.; Barbera, M. C.; Barrow, D.; Nicholson, R. I.; Chiosis,
G.; Brancale, A.; Hamel, E.; Artico, M.; Silvestri, R. J.
Med. Chem. 2006, 49, 947–954.
a further amount of SmI
of the reduction which was observed over a period of 2–
h. The mixture was then treated with excess acetic
2
was added to ensure completion
6
anhydride, left under stirring overnight and extracted 3
times with ethyl acetate. The organic phases were washed
with an aqueous solution of potassium carbonate and
potassium sodium tartrate (1:10 w/w). After evaporation
to dryness the residue was purified by silica gel column
chromatography (eluant cyclohexane/ethyl acetate 1:1) to
give the desired thioacetate. Compound 3a: off-white solid,
ESI(+)-MS m/z = 308 [M+H] ; ESI-HRMS calculated
for C14
kmax (MeOH) 270, 296 nm; H NMR ((CD ) CO) d
+
+
H
14NO
5
S 308.0593 [M+H] , found 308.0570; UV
1
3 2
(
7
(
(
1
1
ppm): 2.26 (6H, s, OCOCH
3
), 2.35 (3H, s, SCOCH
3
),
24. Ilyn, A. P.; Loseva, M. V.; Vvedensky, V. Y.; Putsykina,
E. B.; Tkachenko, S. E.; Kravchenko, D. V.; Khvat, A. V.;
Krasavin, M. Y.; Ivachtchenko, A. V. J. Org. Chem. 2006,
71, 2811–2819.
25. Edge, R.; d’Ischia, M.; Land, E. J.; Napolitano, A.;
Navaratnam, S.; Panzella, L.; Pezzella, A.; Ramsden, C.
A.; Riley, P. A. Pigment Cell Res. 2006, 19, 443–450.
.26 (1H, s), 7.37 (1H, s), 7.56 (1H, d, J = 2.8 Hz), 10.75
13
1H, br s); C NMR ((CD
3 2
) CO) d (ppm): 20.23, 20.80
2 · OCOCH ) 29.80 (SCOCH ), 99.4 (C), 107.1 (CH),
3
3
12.5 (CH), 127.2 (C), 133.2 (CH), 134.3 (C), 138.1 (C),
39.6 (C),168.8, 168.9 (2 · OCOCH ), 195.4 (SCOCH ).
3
3
+
Compound 3b: ESI(+)-MS m/z = 366 [M+H] ; ESI-