E
V. Lösle et al.
Paper
Synthesis
8-(tert-Butyldiphenylsilyloxy)-3,3,5-trimethyl-3,11-dihydropyra-
no[3,2-a]carbazole (5)
Clausenalansine A (1)
A solution of compound 11 (30.4 mg, 57.2 mol) in DMF (1.75 mL)
was stirred at –5 °C under air and 1 M TBAF in THF (70 L, 70 mol)
was added dropwise. The reaction mixture was stirred for 20 min at
–5 °C and then water was added under cooling. The solution was di-
luted with EtOAc, and the organic layer was separated and washed
with water and brine. The combined aqueous layers were extracted
with EtOAc and the combined organic layers were dried over MgSO4.
Removal of the solvent and column chromatography (silica gel, pen-
tane/EtOAc, 2:1, 1 vol % AcOH) of the residue provided 1 as a yellow
solid; yield: 16.7 mg (99%); mp >240 °C (dec).
To a stirred solution of 2-hydroxycarbazole 10 (70.3 mg, 156 mol) in
toluene (3.0 mL) at –78 °C was added 3-methylbut-2-enal (prenal)
(28.7 mg, 341 mol) and then slowly Ti(Oi-Pr)4 (0.18 mL, 0.17 g, 0.61
mmol). The reaction mixture was stirred for 10 min at –78 °C, then
allowed to warm to r.t., and stirred for an additional 4 h. After hydro-
lysis by addition of water (3.0 mL), the organic layer was separated,
and washed first with sat. aq NH4Cl and then with water. The com-
bined aqueous layers were extracted with EtOAc and the combined
organic layers were then washed with brine and dried over MgSO4.
Removal of the solvent and column chromatography (silica gel, pen-
tane/EtOAc, 8:1) of the residue provided pyrano[3,2-a]carbazole 5 as
a yellow viscous oil; yield: 58.4 mg (72%).
1H NMR (500 MHz, DMSO-d6): = 1.07 (s, 9 H), 1.40 (s, 6 H), 2.18 (s, 3
H), 5.75 (dd, J = 9.8, 0.4 Hz, 1 H), 6.70 (ddd, J = 8.5, 2.5, 0.3 Hz, 1 H),
6.85 (d, J = 9.8 Hz, 1 H), 7.13 (dd, J = 8.5, 0.3 Hz, 1 H), 7.33 (dd, J = 2.5,
0.3 Hz, 1 H), 7.41–7.46 (m, 7 H), 7.71–7.73 (m, 4 H), 10.94 (s, 1 H).
13C NMR and DEPT (125 MHz, DMSO-d6): = 15.86 (CH3), 19.12 (C),
26.53 (3 CH3), 27.38 (2 CH3), 75.63 (C), 104.28 (C), 108.82 (CH), 110.78
(CH), 115.81 (C), 116.45 (C, CH), 117.88 (CH), 120.86 (CH), 123.38 (C),
127.98 (4 CH), 128.89 (CH), 130.08 (2 CH), 132.86 (2 C), 134.88 (C),
135.21 (4 CH), 135.98 (C), 148.09 (C), 149.03 (C).
IR (ATR): 3413, 3393, 3298, 2972, 2868, 2030, 2010, 1658, 1639, 1586,
1464, 1258, 1146, 1116, 891, 866, 802, 718, 679 cm–1
.
1H NMR (600 MHz, DMSO-d6): = 1.49 (s, 6 H), 5.91 (d, J = 9.8 Hz, 1
H), 6.87 (dd, J = 8.6, 2.3 Hz, 1 H), 6.91 (d, J = 9.8 Hz, 1 H), 7.27 (d, J = 8.6
Hz, 1 H), 7.40 (dd, J = 2.3, 0.4 Hz, 1 H), 8.20 (d, J = 0.4 Hz, 1 H), 9.08 (br
s, 1 H), 10.33 (s, 1 H), 11.46 (s, 1 H).
13C NMR and DEPT (151 MHz, DMSO-d6): = 27.24 (2 CH3), 77.01 (C),
103.89 (C), 105.32 (CH), 111.59 (CH), 114.84 (CH), 116.84 (CH),
116.97 (C), 117.59 (C), 119.17 (CH), 124.00 (C), 129.70 (CH), 134.45
(C), 141.13 (C), 151.64 (C), 153.59 (C), 187.86 (CHO).
MS (EI): m/z (%) = 293 (13, [M+]), 279 (19), 278 (100), 276 (23), 249
(6), 220 (9), 139 (6).
MS (EI): m/z (%) = 517 (33, [M+]), 503 (75), 502 (100), 460 (19), 444
(17), 222 (28).
UV (MeOH): = 227, 288, 312, 372 (sh) nm.
Anal. Calcd for C18H15NO3: C, 73.71; H, 5.15; N, 4.78. Found: C, 73.73;
H, 5.29; N, 4.69.
For further spectroscopic data, see ref. 7.
8-(tert-Butyldiphenylsilyloxy)-5-formyl-3,3-dimethyl-3,11-di-
hydropyrano[3,2-a]carbazole (11)
X-ray Crystallographic Data for Compound 1
Single crystals of clausenalansine A (1) were obtained by crystalliza-
tion from pentane/MeOH. C18H15NO3, M = 293.31 g mol–1, crystal size:
0.090 × 0.153 × 0.564 mm3, triclinic, space group: P1, a = 8.429(2) Å,
b = 10.978(3) Å, c = 17.384(4) Å, = 71.708(9)°, = 78.951(9)°, =
74.748(10)°, V = 1463.0(6) Å3, Z = 4, calcd = 1.332 g cm–3, = 0.091
mm–1, = 0.71073 Å, T = 150(2) K, θ range = 2.49–28.00°, reflections
collected: 71077, independent reflections: 7039 (Rint = 0.0947), 6193
observed reflections [I ≥ 2(I)], 418 parameters. The structure was
solved by direct methods and refined by full-matrix least squares on
F2; final R indices [I > 2(I)]: R1 = 0.0500, wR2 = 0.1341; max. residual
Pyrano[3,2-a]carbazole 5 (93.1 mg, 180 mol) was dissolved in a mix-
ture of MeOH/THF/H2O (10:3:1, 21 mL) and the solution was cooled to
0 °C. DDQ (92.5 mg, 407 mol) was then added in portions and stir-
ring was continued for 1 h at 0 °C. The reaction was quenched by ad-
dition of 10% aq NaOH, and the aqueous layer was separated and ex-
tracted with EtOAc. The combined organic layers were washed with
brine, dried over MgSO4, and concentrated in vacuo. Column chroma-
tography (silica gel, pentane/EtOAc, 5:1 to 3:1) of the residue provid-
ed compound 11 as a light-yellow solid; yield: 76.5 mg (80%); mp
234–234.5 °C.
electron density: 0.540 e Å–3 16
.
IR (ATR): 3281, 2959, 2929, 2855, 1589, 1460, 1139, 1114, 970, 890,
699, 613 cm–1
.
1H NMR (600 MHz, DMSO-d6): = 1.08 (s, 9 H), 1.48 (s, 6 H), 5.91 (d, J
= 9.9 Hz, 1 H), 6.77 (dd, J = 8.7, 2.3 Hz, 1 H), 6.89 (d, J = 9.9 Hz, 1 H),
7.21 (dd, J = 8.7, 0.4 Hz, 1 H), 7.42–7.48 (m, 6 H), 7.54 (d, J = 2.3 Hz, 1
H), 7.71–7.73 (m, 4 H), 8.11 (s, 1 H), 10.31 (s, 1 H), 11.57 (s, 1 H).
Supporting Information
Supporting information for this article is available online at
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13C NMR and DEPT (151 MHz, DMSO-d6): = 19.13 (C), 26.52 (3 CH3),
27.22 (2 CH3), 77.13 (C), 104.13 (C), 110.14 (CH), 111.48 (CH), 116.77
(CH), 117.25 (2 C), 117.37 (C), 118.12 (CH), 119.27 (CH), 123.88 (C),
128.03 (4 CH), 129.93 (CH), 130.17 (2 CH), 132.63 (C), 135.23 (4 CH),
135.68 (C), 141.22 (C), 149.18 (C), 153.77 (C), 187.91 (CHO).
References
(1) (a) Chakraborty, D. P.; Roy, S. In Progress in the Chemistry of
Organic Natural Products, Vol. 57; Herz, W.; Grisebach, H.; Kirby,
G. W.; Steglich, W.; Tamm, C., Ed.; Springer-Verlag: Wien, 1991,
71. (b) Chakraborty, D. P. In The Alkaloids, Vol. 44; Cordell, G. A.,
Ed.; Academic Press: New York, 1993, 257.
(2) (a) Knölker, H.-J.; Reddy, K. R. Chem. Rev. 2002, 102, 4303.
(b) Knölker, H.-J. Top. Curr. Chem. 2005, 244, 115. (c) Knölker,
H.-J.; Reddy, K. R. In The Alkaloids, Vol. 65; Cordell, G. A., Ed.;
Academic Press: Amsterdam, 2008, 1. (d) Bauer, I.; Knölker, H.-J.
Top. Curr. Chem. 2012, 309, 203. (e) Schmidt, A. W.; Reddy, K. R.;
Knölker, H.-J. Chem. Rev. 2012, 112, 3193.
MS (ESI, +50 V): m/z = 532.6 [M + H+].
UV (MeOH): = 224, 288, 311, 370 (sh) nm.
Fluorescence (MeOH): ex = 311 nm, em = 358 nm.
Anal. Calcd for C34H33NO3Si: C, 76.80; H, 6.26; N, 2.63. Found: C,
76.61; H, 6.17; N, 2.67.
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