Download PDF
Synlett 2008(2): 263-267  
DOI: 10.1055/s-2007-1000933
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of a Calothrixin B Isomer with a Novel 7H-Indolo[2,3-j]phenanthridine-7,13(8H)-dione Structure

Lucie Maingota, Frédéric Thuauda, Drissa Sissoumaa,b, Sylvain Collet*a, André Guingant*a, Michel Evainc
a Laboratoire de Synthèse Organique (LSO), Faculté des Sciences et des Techniques, Université de Nantes, Nantes Atlantique Universités, CNRS, UMR CNRS 6513, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France
Fax: +33(2)51125402; e-Mail: Sylvain.Collet@univ-nantes.fr; e-Mail: Andre.Guingant@univ-nantes.fr;
b Laboratoire de Chimie Organique Structurale, UFR SSMT, Université de Cocody-Abidjan, Ivory Coast
c Institut des Matériaux Jean Rouxel, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 03, France
Further Information

Publication History

Received 10 September 2007
Publication Date:
21 December 2007 (online)

    Permissions and Reprints All articles of this category

Abstract

Synthesis of an N-protected 2-bromo-1H-carbazole-1,4(9H)-dione is reported for the first time. We took full advantage of the high polarization and electrophilic properties of this new compound to engage it in a regioselective hetero-Diels-Alder reaction. The resultant cycloadduct was next transformed to an isomer of the naturally occurring calothrixin B displaying a new 7H-indolo[2,3-j]phenanthridine-7,13(8H)-dione structure.

Key words

2-bromo-1H-carbazole-1,4(9H)-dione - hetero-Diels-Alder reaction - 7H-indolo[2,3-j]phenanthridine-7,13(8H)-dione - calothrixin B isomer

6

Conditions tested from 16 for HBr β-elimination: EtOH, reflux, 1.5 h (4b:6b = 1.5:1); CHCl3, MgBr2 (1 equiv), 40 °C, 4 h (4b:6b = 2:1); SiO2 (4b:6b = 1:1); EtOH, BF3·Et2O, 55 °C, 2 h (4b:6b = 1:1.5).

9

Benzyl 2-Bromo-1,4-dioxo-1 H -carbazole-9(4 H )-carboxylate (6b): orange solid; mp 148 °C. 1H NMR (300 MHz, CDCl3): δ = 5.53 (s, 2 H, OCH2Ph), 7.23 (s, 1 H, H-3), 7.30-7.70 (m, 7 H, HAr), 7.99 (d, J = 8.4 Hz, 1 H, H-8), 8.28 (d, J = 7.5 Hz, 1 H, H-5). 13C NMR (75 MHz, CDCl3): δ = 71.0 (OCH2Ph), 114.5 (C-3), 122.8 (quaternary C), 123.2 (quaternary C), 123.4 (CHAr), 126.1 (CHAr), 128.8 (2 × CHAr), 129.2 (3 × CHAr), 129.7 (CHAr), 133.6 (quaternary C), 133.8 (quaternary C), 137.6 (quaternary C + CHAr), 138.8 (quaternary C), 149.9 (NCO), 170.2 (C-1), 181.2 (C-4). FT-IR (KBr): 3300, 3054, 1755, 1682, 1654 cm-1. MS (CI, NH3): m/z (%) = 427 [M + NH4 +, 79Br], 410 [M + H+, 79Br], 366, 332, 145, 91. HRMS (EI): m/z calcd for C20H12BrNO4: 408.9950; found: 408.9954.

10

C20H12BrNO4: The data set was collected on a Nonius-Bruker Kappa CCD diffractometer, using the Mo-KL2,3 radiation. C20H12BrNO4 (M = 410.2): triclinic, space group P-1, Dc = 1.660 g cm-3, a = 7.1218(3), b = 9.6798(4), c = 13.2182(7) Å, α = 72.048(3)°, β = 84.294(6)°, γ = 71.184(5)°, V = 820.54(7) Å3, Z = 2, λ = 0.71069 Å, µ = 2.532 mm-1, T = 150 K, R(F2) = 0.0547 for 3460 observed reflections [I > 2 σ(I)] and Rw(F2) = 0.1183 for all 4692 reflections. The data have been deposited with the Cambridge Crystallographic Data Centre, CCDC No. 654172.

11

The orientation of addition of 6b to 5 is governed by the bromo substituent. We have already observed such an effect in previous works.12 First observations were reported by Cameron et al.13

14

3,4-Dihydro-2 H -indolo[2,3- j ]phenanthridine-1,7,13 (8 H )-trione (22): To a stirred solution of diene 5 (250 mg, 1.47 mmol) in anhydrous CHCl3 (5 mL) at r.t was added a solution of dienophile 6b (400 mg, 0.98 mmol) in anhydrous CHCl3 (8 mL). After the mixture was heated at 50 °C for 18 h, it was cooled to r.t. and concentrated in vacuo. The residue was purified by column chromatography on silica gel (elution with EtOAc-hexanes, 1:1) to give the cycloadduct 22 (215 mg, 0.68 mmol, 70%) as an orange-red solid: mp >300 °C (CHCl3-hexanes) (dec.). 1H NMR (300 MHz, DMSO): δ = 2.20 (quint, J = 6.3 Hz, 2 H, H-3), 2.91 (t, J = 6.6 Hz, 2 H, H-2), 3.12 (t, J = 6.0 Hz, 2 H, H-4), 7.42 (t, J = 7.5 Hz, 1 H, H-10 or H-11), 7.52 (t, J = 7.5 Hz, 1 H, H-11 or H-10), 7.65 (d, J = 8.4 Hz, 1 H, H-9), 8.12 (d, J = 7.8 Hz, 1 H, H-12), 9.20 (s, 1 H, H-6), 13.27 (br s, 1 H, NH). 13C NMR (75 MHz, DMSO): δ = 21.5 (C-3), 33.0 (C-4), 39.4 (C-2), 114.6 (C-9), 118.7 (quaternary C), 122.8 (CHAr), 124.2 (quaternary C), 124.8 (CHAr), 126.7 (quaternary C), 128.0 (CHAr), 129.8 (quaternary C), 136.7 (quaternary C), 139.0 (quaternary C), 141.4 (quaternary C), 149.3 (C-6), 169.2 (C-7), 176.7 (C-4a), 179.0 (C-13), 199.0 (C-1). FT-IR (KBr): 3287, 2954, 1685, 1655, 1653 cm-1. MS (EI, 70 eV): m/z (%) = 316 (60) [M+], 288 (100), 260 (21), 232 (11), 203 (24), 177 (24), 115 (24). HRMS (EI): m/z calcd for C19H12N2O3: 316.0848; found: 316.0849.
Compound 22 and its regioisomer, arising from the cycloaddition of 4b to diene 5 (a precursor of calothrixin B),2g display distinguishable NMR signals (Δδ = 0.06 ppm).

15

Isolation of benzyl dimethylcarbamate, next to 22, demonstrates that the N-Cbz bond cleavage resulted from the attack of Me2NH·HBr generated in the course of the Diels-Alder primary adduct aromatization process.

17

8 H -Indolo[2,3- j ]phenanthridine-7,13-dione (2): red solid; mp >350 °C. 1H NMR (300 MHz, DMSO): δ = 7.35 (t, J = 7.2 Hz, 1 H, HAr), 7.43 (t, J = 7.2 Hz, 1 H, HAr), 7.56 (d, J = 8.4 Hz, 1 H, HAr), 7.81 (t, J = 7.6 Hz, 1 H, HAr), 7.91 (t, J = 7.6 Hz, 1 H, HAr), 8.10 (d, J = 8.4 Hz, 1 H, HAr), 8.20 (d, J = 8.0 Hz, 1 H, HAr), 9.50 (s, 1 H, H-6), 9.65 (d, J = 8.4 Hz, 1 H, HAr), 13.10 (br s, 1 H, NH). 13C NMR (75 MHz, DMSO): δ = 114.0 (CHAr), 118.5 (quaternary C), 122.3 (CHAr), 123.0 (quaternary C), 124.0 (2 × quaternary C), 124.3 (CHAr), 127.1 (CHAr), 127.9 (CHAr), 129.7 (CHAr), 129.9 (CHAr), 131.8 (CHAr), 134.1 (quaternary C), 135.4 (quaternary C), 138.4 (quaternary C), 146.9 (CHAr), 151.8 (quaternary C), 177.6 (C-7), 186.7 (C-13). FT-IR (KBr): 3444, 1659, 1535 cm-1. MS (EI, 70 eV): m/z (%) = 298 (100) [M+], 270 (55), 242 (26), 241 (26), 214 (38). HRMS (EI): m/z calcd for C19H10N2O2: 298.0742; found: 298.0743.