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Synlett 2008(4): 505-508  
DOI: 10.1055/s-2008-1042764
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Facile Synthesis of Telisatin A via Microwave-Promoted Annulation and ­Reformatsky Reaction

Nopporn Thasana*a,b, Ben Bjerke-Krollb, Somsak Ruchirawat*a-c
a Chulabhorn Graduate Institute, Vipavadee Rangsit Highway, Bangkok 10210, Thailand
Fax: +66(2)5742027; e-Mail: nopporn@cri.or.th;
b Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, Vipavadee Rangsit Highway, Bangkok 10210, Thailand
c Programme on Research and Development of Synthetic Drugs, Institute of Science and Technology for Research and Development, Mahidol University, Salaya Campus, Nakhonpathom 73170, Thailand
Further Information

Publication History

Received 15 August 2007
Publication Date:
12 February 2008 (online)

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Abstract

A facile one-pot synthesis of 2,3-dioxopyrrolo[2,1-a]isoquinolines is reported involving the ring formation of aryl pyruvate derivatives with 3,4-dihydroisoquinolines under basic conditions and utilizing the Reformatsky reaction. Using microwave irradiation, the required compounds were obtained in moderate to good yields.

Key words

microwave - annulation - Reformatsky reaction - dioxo­pyrrolo[2,1-a]isoquinoline - dioxoaporphine

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Synthesis of 2,3-Dioxopyrrolo[2,1- a ]isoquinoline 2; Typical Procedure (Conditions C): A mixture of imines 4 (0.1 mmol), aryl pyruvates 5 (0.1 mmol) and NaOMe (0.1 mmol) in DMF (1 mL) was irradiated using microwave. The microwave run time was set to 2 min, with power at 300 W, temperature at 150 °C, and pressure at 100 psi, and the conditions were maintained for 10 min. The reaction was quenched with H2O and extracted with EtOAc, dried (Na2SO4) and evaporated in vacuo to yield a red residue. The residue was purified by column chromatography, affording crystals of 2 after recrystallization in moderate yields (54-78%).
Conditions D: A mixture of imines 4 (0.1 mmol), aryl pyruvates 5 (0.1 mmol), copper powder (0.1 mmol) and zinc powder (0.1 mmol) in DMF (1 mL) was irradiated using microwave. The microwave run time was set to 2 min, with power at 300 W, temperature at 150 °C, and pressure at 100 psi, and the conditions were maintained for 10 min. The reaction was quenched with H2O and extracted with EtOAc, dried (Na2SO4) and evaporated in vacuo to yield a red residue. The residue was purified by column chromatog
raphy, affording crystals of 2 after recrystallization in moderate to good yields (60-82%). Compound 2a: deep-red solid; mp 178-179 °C (EtOAc-hexane). IR (CHCl3): 3020, 1745, 1701, 1580, 1492, 1290 cm-1. 1H NMR (200 MHz, CDCl3): δ = 3.09 (t, J = 6.2 Hz, 2 H), 3.33 (s, 3 H), 3.85 (t, J = 6.2 Hz, 2 H), 3.96 (s, 3 H), 6.77 (s, 1 H), 6.95 (s, 1 H), 7.37 (m, 5 H). 13C NMR (50 MHz, CDCl3): δ = 28.6, 36.6, 55.3, 56.2, 111.2, 112.2, 116.8, 127.9, 128.9, 130.2, 130.3, 132.8, 147.9, 153.5, 157.4, 158.3, 165.9, 183.1. MS (EI): m/z (%) = 263 (7), 306 (100), 307 (26), 335 (58) [M+]. HRMS (FAB): m/z [M + H+] calcd for C20H17NO4: 336.1236; found: 336.1234.
Compound 2b: wine-red solid; mp 198-199 °C (EtOAc-hexane; lit [8c] 176-178 °C). IR (KBr): 1746, 1692, 1575, 1514, 1396, 1290, 1223 cm-1. 1H NMR (200 MHz, CDCl3): δ = 3.11 (t, J = 6.2 Hz, 2 H), 3.30 (s, 3 H), 3.89 (t, J = 6.2 Hz, 2 H), 3.95 (s, 3 H), 6.65 (s, 1 H), 6.78 (s, 1 H), 7.31 (m, 3 H), 7.71 (d, J = 7.2 Hz, 1 H). 13C NMR (50 MHz, CDCl3): δ = 28.4, 36.4, 55.2, 56.2, 107.9, 111.2, 111.5, 116.9, 125.9, 128.0, 129.9, 132.5, 132.8, 133.2, 148.3, 153.8, 158.1, 158.4, 181.6. MS (EI): m/z (%) = 306 (83), 334 (100), 384 (34), 386 (31), 413 (31) [M+], 415 (31) [M+ + 2]. HRMS (FAB): m/z [M + H+] calcd for C20H16BrNO4: 414.0341; found: 414.0343.
Compound 2c: deep-red solid; mp 178-179 °C (EtOAc-hexane). IR (CHCl3): 2941, 1742, 1692, 1573, 1472, 1403, 1343, 1299, 1111, 1029 cm-1. 1H NMR (200 MHz, CDCl3): δ = 3.10 (t, J = 6.2 Hz, 2 H), 3.30 (s, 3 H), 3.81 (t, J = 6.2 Hz, 2 H), 3.89 (s, 3 H), 3.95 (s, 3 H), 6.82 (s, 1 H), 7.34 (m, 3 H), 7.37 (m, 2 H). 13C NMR (100 MHz, CDCl3): δ = 21.7, 36.1, 55.2, 61.0, 61.1, 109.1, 119.3, 125.6, 128.0, 128.9, 130.1, 130.2, 147.1, 147.7, 150.5, 151.9, 157.1, 157.9, 183.4. MS (EI): m/z (%) = 237 (37), 336 (100), 365 (60) [M+]. HRMS (FAB): m/z [M + H+] calcd for C21H19NO5: 366.1341; found: 366.1338.
Compound 2d: wine-red solid; mp 153-155 °C (EtOAc-hexane). IR (KBr): 1747, 1703, 1576, 1467, 1425, 1397, 1341, 1109, 1024 cm-1. 1H NMR (200 MHz, CDCl3): δ = 3.11 (t, J = 6.6 Hz, 2 H), 3.20 (s, 3 H), 3.75 (t, J = 6.2 Hz, 2 H), 3.81 (s, 3 H), 3.87 (s, 3 H), 6.46 (s, 1 H), 7.20 (m, 2 H), 7.33 (t, J = 7.0 Hz, 1 H), 7.64 (d, J = 7.2 Hz, 1 H). 13C NMR (50 MHz, CDCl3): δ = 21.7, 36.2, 55.2, 61.0, 61.1, 108.6, 119.4, 125.4, 125.8, 128.0, 129.9, 132.3, 132.7, 133.2, 147.0, 150.6, 152.3, 157.9, 158.0, 182.0. MS (EI): m/z (%) = 336 (54), 364 (100), 414 (34), 416 (36), 443 (93) [M+], 445 (95) [M+ + 2]. HRMS (FAB): m/z [M + H+] calcd for C21H18BrNO5: 444.0447; found: 444.0449.