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Synlett 2009(3): 469-471  
DOI: 10.1055/s-0028-1087551
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Biogenetic-Like Cyclization of Denudatenone A to Dolabellane-Type Diterpenoids Induced by Samarium(II) Iodide: A Ketyl-Olefin Radical Coupling Reaction Forming Five-Membered Carbocycles

Masakazu Sono*, Megumi Hanaoaka, Toshihiro Hashimoto, Yoshinori Asakawa, Motoo Tori*
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 7708514, Japan
Fax: +81(88)6553051; e-Mail: sono@ph.bunri-u.ac.jp;
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Publication History

Received 14 October 2008
Publication Date:
21 January 2009 (online)

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Abstract

Denudatenone A was treated with SmI2 in THF with or without the additives to form dolabellane-type diterpenoids as a result of 5-exo-trig mode of cyclization. The cyclized products were effectively obtained when water or HMPA was added. This constitutes the biogenetic-type transformation of vibsane to dolabellane diterpenoids.

Key words

samarium diiodide - cyclization - reduction - denudatenone A - diterpenes

    References and Notes

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General Procedure: All reactions were carried out in an argon atmosphere. Anhydrous solvents were purchased from the Kanto Chemical Co., Inc. Reagents were purchased at the highest commercial quality and were used without further purification. The IR spectra were measured on a JASCO FT/IR 500 spectrophotometer. Mass spectra, including high-resolution spectra, were recorded on a JEOL JMS-700 MStation instrument. ¹H NMR and ¹³C NMR spectra were measured on Varian Unity 600 (600 MHz and 150 MHz, respectively) and Varian Unity 200 (200 MHz and 50 MHz, respectively) spectrometers. Chemcopak Nucleosil 50-5 (4.6 × 250 mm) with a solvent system of hexane-EtOAc was used for HPLC (a JASCO pump system). Silica gel 60 (70-230 mesh, Fuji Sylisia) was used for column chromatography. Silica gel BW-300 (200-400 mesh, Fuji Sylisia) was used for column chromatography and silica gel 60F254 plate (0.25 mm, Merck) was used for TLC.
Reaction of Denudatenone A with SmI 2 : To a stirred solution of SmI2 (0.1 M in THF, 15.2 mL, 1.5 mmol) and H2O (135 mg, 7.5 mmol) was added a solution of denudatenone A (1; 75.3 mg, 0.25 mmol) in THF (5 mL) at r.t. and the mixture was stirred for 4.5 h. The reaction was quenched with a sat. aq solution of Rochelle’s salt. Organic materials were extracted with Et2O, washed with brine, and dried (MgSO4). The products were purified by silica gel flash chromatography (hexane-EtOAc, in a gradient) to afford 2 (25.7 mg, 34%), 3 (2.5 mg, 3.2%), and 4 (3.6 mg, 5%) as well as 1 (18.8 mg, 25%).
Compound 2: [α]D +72.0 (c = 1.0, CHCl3). ¹H NMR (600 MHz, CDCl3): δ = 0.92 (d, 3 H, J = 6.9 Hz, H-19), 0.99 (d,
3 H, J = 6.9 Hz, H-20), 1.06 (s, 3 H, H-15), 1.42 (m, 1 H,
H-13), 1.39 (m, 1 H, H-14), 1.51 (dd, 1 H, J = 8.8, 3.3 Hz, H-11), 1.55 (t, 3 H, J = 1.4 Hz, H-16), 1.59 (m, 1 H, H-10), 1.65 (m, 1 H, H-13), 1.67 (m, 1 H, H-14), 1.71 (m, 1 H, H-2), 1.72 (d, 3 H, J = 0.8 Hz, H-17), 1.74 (m, 1 H, H-10), 1.86 (m, 1 H, H-18), 1.88 (m, 1 H, H-9), 2.04 (t, 1 H, J = 11.0 Hz, H-5), 2.17 (dd, 1 H, J = 13.5, 12.9 Hz, H-2), 2.35 (dt, 1 H,
J = 14.6, 4.1 Hz, H-9), 2.56 (dd, 1 H, J = 11.5, 5.2 Hz, H-5), 4.63 (td, 1 H, J = 10.2, 5.2 Hz, H-6), 5.14 (dt, 1 H, J = 9.9, 1.4 Hz, H-7), 5.21 (d, 1 H, J = 11.8 Hz, H-3). ¹³C NMR (150 MHz, CDCl3): δ = 16.8 (C-16), 17.9 (C-20), 18.9 (C-19), 19.7 (C-17), 23.7 (C-15), 25.9 (C-10), 30.5 (C-13), 35.0 (C-18), 35.7 (C-9), 40.8 (C-14), 43.2 (C-2), 44.4 (C-1), 46.0 (C-11), 49.0 (C-5), 66.7 (C-6), 87.6 (C-12), 126.5 (C-3), 129.3 (C-7), 132.8 (C-4), 137.7 (C-8). MS (CI): m/z = 307 [M + H]+, 306, 305, 290, 289, 288, 271 (base), 221, 219. HRMS (CI): m/z [M + H]+ calcd for C20H35O2: 307.2637; found: 307.2640. IR: 3350 cm-¹.
Compound 3: [α]D +34.3 (c = 0.8, CHCl3). ¹H NMR (600 MHz, CDCl3): δ = 0.91 (d, 3 H, J = 6.8 Hz, H-20), 0.99 (d,
3 H, J = 6.8 Hz, H-19), 1.01 (s, 3 H, H-15), 1.36 (m, 1 H, H-14), 1.41 (m, 1 H, H-10), 1.51 (m, 1 H, H-13), 1.53 (m, 1 H, H-14), 1.54 (m, 1 H, H-11), 1.60 (s, 3 H, H-16), 1.66 (m,
1 H, H-10), 1.74 (m, 1 H, H-2), 1.76 (m, 1 H, H-13), 1.78 (d, 3 H, J = 1.4 Hz, H-17), 1.84 (sept, 1 H, J = 6.8 Hz, H-18), 1.96 (ddd, 1 H, J = 13.7, 10.6, 3.7 Hz, H-9), 2.02 (t, 1 H, J = 11.0 Hz, H-5), 2.33 (dt, 1 H, J = 13.7, 3.7 Hz, H-9), 2.47 (t, 1 H, J = 12.6 Hz, H-2), 2.57 (dd, 1 H, J = 11.6, 5.2 Hz, H-5), 4.68 (td, 1 H, J = 11.0, 5.2 Hz, H-6), 5.08 (dt, 1 H, J = 11.0, 1.4 Hz, H-7), 5.18 (dd, 1 H, J = 12.6, 2.2 Hz, H-3). ¹³C NMR (150 MHz, CDCl3): δ = 16.7 (C-16), 17.9 (C-20), 19.0 (C-19), 19.9 (C-17), 23.8 (C-15), 28.4 (C-10), 31.5 (C-18), 35.1 (C-13), 35.9 (C-9), 40.5 (C-14), 44.1 (C-1), 44.9 (C-2), 49.2 (C-5), 51.5 (C-11), 66.9 (C-6), 87.1 (C-12), 126.5 (C-3), 129.6 (C-7), 133.5 (C-4), 138.2 (C-8). MS (CI): m/z = 306 [M]+, 305, 289, 271 (base). HRMS (CI): m/z [M]+ calcd for C20H34O2: 306.2559; found: 306.2570. IR: 3400 cm-¹.
Compound 4: [α]D +88.5 (c = 0.3, CHCl3). ¹H NMR (600 MHz, CDCl3): δ = 1.17 (s, 3 H, H-15), 1.41-1.46 (m, 4 H, H-2, H-10, H-14), 1.47 (s, 3 H, H-16) 1.59 (s, 3 H, H-20), 1.60 (s, 3 H, H-19), 1.64 (m, 1 H, H-14), 1.78 (d, 3 H, J = 1.1 Hz, H-17), 2.09 (t, 1 H, J = 11.3 Hz, H-5), 2.03 (m, 1 H, H-2), 2.05 (m, 1 H, H-9), 2.20 (m, 2 H, H-13), 2.29 (m, 1 H, H-9), 2.28 (m, 1 H, H-11), 2.65 (dd, 1 H, J = 11.3, 5.5 Hz, H-5), 4.65 (td, 1 H, J = 11.3, 5.5 Hz, H-6), 5.11 (d, 1 H, J = 10.0 Hz, H-7), 5.37 (dd, 1 H, J = 12.5, 3.3 Hz, H-3). ¹³C NMR (150 MHz, CDCl3): δ = 16.4 (C-17), 16.5 (C-16), 21.1 (C-19), 21.7 (C-20), 23.6 (C-15), 27.3 (C-10), 28.2 (C-13), 38.0 (C-9), 38.6 (C-2), 40.5 (C-14), 41.9 (C-11), 48.6 (C-1), 49.4 (C-5), 66.4 (C-6), 122.3 (C-18), 128.3 (C-3), 131.8 (C-7), 133.1 (C-4), 137.2 (C-8), 142.1 (C-12). MS (CI): m/z = 288 [M]+, 271 (base), 219, 191, 89. HRMS (CI): m/z [M]+ calcd for C20H32O: 288.2453; found: 288.2461. IR: 3390 cm-¹.