760
G. Wille, W. Steglich
PAPER
IR (KBr): = 3436 (br s), 2980 (m), 1783 (s), 1734 (s), 1157 (s), 767
(m), 747 cm-1 (m).
In conclusion, the bacterial pigments deoxyviolacein (1a)
and violacein (1b) were synthesised in 20% and 14%
overall yields, respectively, from simple building blocks.
1H NMR (300 MHz, CDCl3): = 1.35 (s, 9 H, t-C4H9), 1.66 (s, 9 H,
t-C4H9), 2.12 (m, 1 H, 3-H), 2.50 (m, 2 H, 2-H), 2.71 (m, 1 H, 3-H),
5.48 (dd, 1 H, J = 2.5, 8 Hz, 4-H), 7.22 (t, 1 H, J = 8 Hz, 5'-H), 7.36
(t, 1 H, J = 7.5 Hz, 6'-H), 7.40 (s, 1 H, 2'-H), 7.50 (d, 1 H, J = 8 Hz,
4'-H), 8.18 (d, 1 H, J = 8.5 Hz, 7'-H).
13C NMR (75 MHz, CDCl3): = 25.2 (CH2), 27.5 [OC(CH3)3], 27.9
[OC(CH3)3], 31.1 (CH2), 54.5 (C-4), 82.7 [OC(CH3)3], 83.7
[OC(CH3)3], 115.3 (CH), 118.4 (CH), 121.1 (CH), 121.2, 122.5
(CH), 124.6 (CH), 127.5 (C-3a'), 135.7 (C-7a'), 149.1 (C=O, Boc),
149.4 (C=O, Boc), 174.0 (C=O).
All solvents were dried and purified using standard techniques. Re-
actions requiring anhydrous conditions were carried out under ar-
gon in oven-dried vessels. Anhydrous and air sensitive liquids were
handled via syringes. While THF was distilled from sodium/ben-
zophenone, EtOH was purchased as anhydrous solvent and stored
over molecular sieves. Petroleum ether refers to the fraction bp 40–
60°C. All reactions were monitored by TLC (Merck silica gel 60
F
254 plates, 0.25 mm) using UV light (254 nm) as visualising agent.
MS (FAB): m/z (%) = 423 (56, M+ + Na), 400 (4, M+), 344 (7, M+ –
C4H8), 323 (100, M+ – Boc + Na), 267 (42), 244 (15, M+ – Boc –
C4H8), 200 (7, M+ – 2 Boc), 154 (8), 84 (5, C4H6NO+), 57 (99,
Flash column chromatography was performed on Merck silica gel
60 (0.043–0.063 mm). Mps (uncorrected) were determined on a Re-
ichard Kofler micro hot-stage apparatus. IR spectra (KBr pellets)
were recorded on a Perkin-Elmer FT 1000 or 1420 Ratio Recording
spectrometer. UV spectra were recorded on a Perkin-Elmer Lambda
16 spectrometer. NMR shifts (in ppm) were calibrated with the re-
sidual undeuterated solvent as the internal reference. 1H NMR and
13C NMR spectra were recorded on Bruker ARX 300 and 600 in-
struments. The characterisation of the 13C NMR signals was based
on DEPT-135 experiments. The 13C NMR signals of 1a were as-
signed in detail with HMBC. Mass spectra and HRMS spectra were
recorded on a Finnigan MAT 90 or MAT 95 Q instrument, using
electron impact ionisation at 70 eV or fast atom bombardment in a
4-nitrobenzyl alcohol matrix.
+
C4H9 ).
HRMS: m/z calcd for C22H28N2O5Na: 423.1896, found: 423.1862.
2-(5-Benzyloxy-1-tert-butyloxycarbonyl-1H-indol-3-yl)-5-ox-
opyrrolidine-1-carboxylic Acid tert-Butyl Ester (6b)
The protocol described for 6a was repeated with 5b (378 mg, 1.23
mmol) and Boc2O (591 mg, 2.71 mmol). Compound 6b (516 mg,
85%) was obtained as a sticky foam; Rf 0.37 (petroleum ether-
EtOAc, 2:1).
IR (KBr): = 3438 (br m), 2933 (s), 1784 (s), 1731 (s), 1257 (s), 767
(m), 742 cm-1 (m).
1H NMR (300 MHz, acetone-d6): = 1.34 (s, 9 H, t-C4H9), 1.66 (s,
9 H, t-C4H9), 2.01 (m, 1 H, 3-H), 2.42–2.70 (m, 3 H, 2-H, 3-H), 5.18
(s, 2 H, OCH2), 5.51 (dd, 1 H, J = 8, 2 Hz, 4-H), 7.08 (d, 1 H, J = 9
Hz, 6'-H), 7.27 (s, 1 H, 2'-H), 7.34 (d, 1 H, J = 7 Hz, C6H5), 7.39 (t,
2 H, J = 7 Hz, C6H5), 7.47 (d, 2 H, J = 7 Hz, C6H5), 7.50 (s, 1 H, 4'-
H), 8.08 (d, 1 H, J = 9 Hz, 7'-H).
13C NMR (75 MHz, acetone-d6): = 26.4 (CH2, C-3), 28.5
[OC(CH3)3], 28.7 [OC(CH3)3], 32.3 (CH2, C-2), 55.8 (CH, C-4),
71.5 (OCH2), 82.8 [OC(CH3)3], 84.8 [OC(CH3)3], 104.9 (CH),
115.2 (CH), 117.3 (CH), 123.3, 123.6 (CH), 128.9 (2 CH, C6H5),
129.0 (CH), 129.7 (2 CH, C6H5), 130.3, 138.9 (C-7a'), 150.5
(C=O, Boc), 151.0 (C=O, Boc), 156.4 (C-5'), 174.2 (C=O).
5-(5-Benzyloxy-1H-indol-3-yl)-pyrrolidin-2-one (5b)
To a solution of 3b17 (1.88 g, 8.4 mmol) and 411 (0.70 g, 8.4 mmol)
in THF (35 mL) was added one drop of concd HCl. After refluxing
for 4 h, the mixture was cooled to r.t. and diluted with EtOAc (40
mL). The organic layer was washed with 5% aq NaHCO3 (2 20
mL), H2O (20 mL) and brine, dried (MgSO4) and concentrated in
vacuo. Purification of the yellow oil by flash chromatography on
silica gel (petroleum ether-EtOAc, 1:1 EtOAc, 10% gradient) af-
forded 5b (2.19 g, 85%) as pale-yellow plates; mp 156°C; Rf 0.14
(EtOAc).
IR (KBr): = 3414 (br s), 3271 (br s), 2925 (br w), 1680 (br s), 1625
(m), 1281 (m), 738 (m), 697 cm-1 (m).
MS (EI): m/z (%) = 506 (9, M+), 450 (7, M+ – C4H8), 406 (12, M+ –
1H NMR (300 MHz, CDCl3): = 2.21 (m, 1 H, 3-H), 2.43 (m, 2 H,
2-H), 2.57 (m, 1 H, 3-H), 5.00 (dd, 1 H, J = 6.5, 7.0 Hz, 4-H), 5.12
(s, 2 H, OCH2), 6.87 (dd, 1 H, J = 9, 2 Hz, 6'–H), 7.23 (d, 1 H, J = 2
Hz, 2'-H), 7.26 (d, 1 H, J = 2 Hz, 4'-H), 7.31 (dd, 1 H, J = 7.5, 1.5
Hz, C6H5), 7.32 (d, 1 H, J = 9 Hz, 7'-H), 7.39 (t, 2 H, J = 7.5 Hz,
C6H5), 7.50 (d, 2 H, J = 7.5 Hz, C6H5), 10.10 (br s, 2 H, NH).
Boc), 394 (5), 350 (39, M+ – Boc – C4H8), 306 (21, M+ – 2 Boc),
+
259 (5), 215 (22, M+ – 2 Boc – C7H7), 91 (100, C7H7 ), 57 (35,
+
C4H9 ).
HRMS: m/z calcd for C29H34N2O6: 506.2417, found: 506.2456.
13C NMR (75 MHz, CDCl3): = 28.5 (CH2, C-3), 30.0 (CH2, C-2),
50.7 (CH, C-4), 70.1 (OCH2), 101.7 (CH), 111.7 (CH), 111.8 (CH),
115.4 (C-3'), 121.8 (CH), 124.8, 126.8 (2 CH, C6H5), 127.0 (CH),
127.7 (2 CH, C6H5), 131.7, 136.9, 151.9 (C-5'), 177.0 (C=O).
2,3-Dioxo-2,3-dihydroindole-1-carboxylic Acid tert-Butyl Ester
(7)
To a solution of isatin (3.68 g, 25.03 mmol) in anhyd THF (100 mL)
was added Boc2O (2.29 g, 10.5 mmol) and a catalytic amount of
DMAP at 10°C. The mixture was stirred at r.t. overnight and con-
centrated in vacuo. The residue was suspended in petroleum ether
and treated with anhyd THF at ~50°C until a clear solution resulted.
Crystallisation at –20°C afforded 7 (5.49 g, 89%) as a yellow amor-
phous solid; mp 132°C; decomposition on TLC (SiO2).
MS (EI): m/z (%) = 306 (81.5, M+), 289 (6), 223 (5), 215 (38, M+ –
C7H7), 187 (8, M+ – C7H7 – CO), 172 (13, M+ – C7H7 – HNCO), 160
+
(7, M+ – C7H7 – HNCOCH2), 131 (6, C8H5O+), 91 (100, C7H7 ).
HRMS: m/z calcd for C19H18N2O2: 306.1368, found: 306.1368.
UV/VIS (CH3CN): max (log ) = 292.5 (3.69), 380.5 nm (2.70).
2-(1-tert-Butyloxycarbonyl-1H-indol-3-yl)-5-oxo-pyrrolidine-1-
carboxylic Acid tert-Butyl Ester (6a); Typical Procedure
To a solution of 5a11,12 (1.00 g, 5.00 mmol) in anhyd THF (50 mL)
was added Boc2O (2.29 g, 10.50 mmol) and a catalytic amount of
DMAP at 0°C. The mixture was allowed to warm to r.t. overnight,
and the solvent was evaporated in vacuo. Purification of the crude
material by flash chromatography on silica gel (petroleum ether-
EtOAc, 3:1) afforded 6a (1.66 g, 83%) as a sticky foam; Rf 0.73 (pe-
troleum ether-EtOAc, 5:1).
IR (KBr): = 3447 (br m), 2984 (w), 1802 (m), 1782 (m), 1744 (s),
1610 (s), 765 cm-1 (m).
1H NMR (300 MHz, acetone-d6): = 1.64 (s, 9 H, t-C4H9), 7.37 (t,
1 H, J = 6.9 Hz), 7.74 (d, 1 H, J = 6.6 Hz), 7.81 (t, 1 H, J = 8.1 Hz),
8.12 (d, 1 H, J = 8.4 Hz).
13C NMR (75 MHz, acetone-d6): = 29.0 [OC(CH3)3], 86.0
[OC(CH3)3], 118.3 (CH), 120.9, 126.1 (CH), 126.8 (CH), 139.9
(CH), 150.2, 150.3 (C=O, Boc), 157.3 (NC=O), 182.1 (C=O).
Synthesis 2001, No. 5, 759–762 ISSN 0039-7881 © Thieme Stuttgart · New York