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Synlett 2016; 27(04): 616-620
DOI: 10.1055/s-0035-1560988
DOI: 10.1055/s-0035-1560988
letter
Efficient Synthesis of (–)-Hanishin, (–)-Longamide B, and (–)-Longamide B Methyl Ester through Piperazinone Formation from 1,2-Cyclic Sulfamidates
Further Information
Publication History
Received: 14.09.215
Accepted after revision: 20 October 2015
Publication Date:
09 December 2015 (online)
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Abstract
We describe a simple chiral-pool synthesis of (–)-longamide B, (–)-longamide B methyl ester, and (–)-hanishin. The key feature of the total synthesis is the formation of a piperazinone from a 1,2-cyclic sulfamidate and methyl 2-pyrrolecarboxylate, which permits efficient construction of the pyrrolopiperazinone core scaffold.
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References and Notes
- 1 Cafieri F, Fattorusso E, Taglialatela-Scafati O. J. Nat. Prod. 1998; 61: 122
- 2 Umeyama A, Ito S, Yuasa E, Arihara S, Yamada T. J. Nat. Prod. 1998; 61: 1433
- 3 Mancini I, Guella G, Amade P, Roussakis C, Pietra F. Tetrahedron Lett. 1997; 38: 6271
- 4a Patel J, Pelloux-Léon N, Minassian F, Vallée Y. J. Org. Chem. 2005; 70: 9081
- 4b Trost BM, Osipov M, Dong G. J. Am. Chem. Soc. 2010; 132: 15800
- 4c Trost BM, Dong G. Org. Lett. 2007; 9: 2357
- 4d Cheng G, Wang X, Bao H, Cheng C, Liu N, Hu Y. Org. Lett. 2012; 14: 1062
- 4e Adhikary ND, Kwon S, Chung W.-J, Koo S. J. Org. Chem. 2015; 80: 7693
- 5 Bower JF, Rujirawanich J, Gallagher T. Org. Biomol. Chem. 2010; 8: 1505
- 6a Williams AJ, Chakthong S, Gray D, Lawrence RM, Gallagher T. Org. Lett. 2003; 5: 811
- 6b Bower JF, Švenda J, Williams AJ, Charmant JP, Lawrence RM, Szeto P, Gallagher T. Org. Lett. 2004; 6: 4727
- 6c So SM, Yeom C.-E, Cho SM, Choi SY, Chung YK, Kim BM. Synlett 2008; 702
- 6d Hirschhäuser C, Parker JS, Perry MW, Haddow MF, Gallagher T. Org. Lett. 2012; 14: 4846
- 6e Bandini M, Eichholzer A, Tragni M, Umani-Ronchi A. Angew. Chem. Int. Ed. 2008; 47: 3238
- 7a Bower JF, Szeto P, Gallagher T. Chem. Commun. 2005; 793
- 7b Bower JF, Riis-Johannessen T, Szeto P, Whitehead AJ, Gallagher T. Chem. Commun. 2007; 728
- 8a Richter HG. F, Adams DR, Benardeau A, Bickerdike MJ, Bentley JM, Blench TJ, Cliffe IA, Dourish C, Hebeisen P, Kennett GA, Knight AR, Malcolm CS, Mattei P, Misra A, Mizrahi J, Monck NJ. T, Plancher JM, Roever S, Roffey JR. A, Taylor S, Vickers SP. Bioorg. Med. Chem. Lett. 2006; 16: 1207
- 8b Boyer SJ, Burke J, Guo X, Kirrane TM, Snow RJ, Zhang Y, Sarko C, Soleymanzadeh L, Swinamer A, Westbrook J, DiCapua F, Padyana A, Kugler S, O’Neill MM. Bioorg. Med. Chem. Lett. 2012; 22: 733
- 8c Shiokawa Z, Hashimoto K, Saito B, Oguro Y, Sumi H, Yabuki M, Yoshimatsu M, Kosugi Y, Debori Y, Morishita N, Dougan DR, Snell GP, Yoshida S, Ishikawa T. Bioorg. Med. Chem. 2013; 21: 7938
- 9 Nishiguchi S, Sydnes MO, Taguchi A, Regnier T, Kajimoto T, Node M, Yamazaki Y, Yakushiji F, Kiso Y, Hayashi Y. Tetrahedron 2010; 66: 314
- 10 Banwell MG, Bray AM, Willis AC, Wong DJ. New J. Chem. 1999; 23: 687
- 11 (4S)-4-(2-Hydroxyethyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (20) t-BuOK (33 mg, 0.29 mmol) was added to a mixture of sulfamidate 15 (101 mg, 0.27 mmol) and methyl pyrrole-2-carboxylate (8) (33 mg, 0.32 mmol) in MeCN (5.0 mL) at 0 °C, and the mixture was stirred at r.t. for 1.5 h. The reaction was quenched with 10% aq citric acid, and the mixture was extracted with EtOAc. The extracts were washed with sat. aq NaHCO3 and brine, then dried (MgSO4) and concentrated under reduced pressure. To a mixture of the residue in MeOH (2.0 mL) was added 4 M HCl in 1,4-dioxane (2.0 mL) at r.t., and the mixture was stirred at r.t. for 1 h. The mixture was evaporated under reduced pressure and the residue was washed with Et2O and dried under reduced pressure. A mixture of the residue and Et3N (0.22 mL, 1.6 mmol) in MeOH (7.0 mL) was stirred at r.t. for 1.5 h and then overnight at 50 °C. The mixture was the concentrated under reduced pressure and the residue was purified by column chromatography (silica gel, 10% MeOH–EtOAc) to give 20 as an off-white solid. Yield: 36 mg (75%); mp 130–134 °C; [α]D 27 –76.8 (c 0.59, MeOH). 1H NMR (400 MHz, CD3OD): δ = 6.93 (dd, J = 2.8, 1.6 Hz, 1 H), 6.75 (dd, J = 4.0, 1.2 Hz, 1 H), 6.11 (dd, J = 3.6, 2.4 Hz, 1 H), 4.34–4.38 (m, 1 H), 3.72 (dd, J = 13.2, 4.4 Hz, 1 H), 3.51–3.57 (m, 1 H), 3.35–3.42 (m, 2 H), 1.81–1.94 (m, 2 H). 13C NMR (100 MHz, CD3OD): δ = 163.38, 125.33, 123.94, 114.84, 110.27, 59.06, 52.47, 45.43, 36.43. HRMS-ESI: m/z [M + Na] calcd for C9H12N2NaO2: 203.0791; found: 203.0794. (4S)-6,7-Dibromo-4-(2-hydroxyethyl)-3,4-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one (21) NBS (87 mg, 0.49 mmol) was added to a solution of 20 (44 mg, 0.24 mmol) in DMF (4.0 mL) at –20 °C, and the mixture was stirred at the 20 °C for 15 min then at r.t. overnight. The reaction was then quenched with sat. aq NaHCO3 and extracted with EtOAc. The extracts were washed with H2O and brine then dried (MgSO4) and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 5% MeOH–EtOAc) to give a colorless solid. Yield: 72 mg (87%); mp 139–142 °C; [α]D 27 –25.6 (c 0.23, MeOH). 1H NMR (400 MHz, CD3OD): δ = 6.91 (s, 1 H), 4.57–4.60 (m, 1 H), 3.80 (ddd, J = 13.8, 4.4, 0.8 Hz, 1 H), 3.63–3.69 (m, 3 H), 1.94–2.02 (m, 1 H), 1.80–1.87 (m, 1 H). 13C NMR (100 MHz, CD3OD): δ = 159.72, 124.63, 115.85, 106.89, 100.72, 59.12, 52.34, 43.10, 34.39. HRMS-ESI: m/z [M + Na] calcd for C9H10Br2N2NaO2: 360.9005; found: 360.8996. (S)-(–) -Longamide B (1) White solid; yield: 51 mg (74%); mp 225–227 °C; [α]D 28 –5.6 (c 0.40, MeOH) {Lit.4a mp 208–210 °C; [α]D 20 –5.51 (c 1, MeOH)}. 1H NMR (400 MHz, CD3OD): δ = 6.93 (s, 1 H), 4.78–4.81 (m, 1 H), 3.88 (ddd, J = 13.8, 4.4, 1.6 Hz, 1 H), 3.66 (dd, J = 14.0, 0.8 Hz, 1 H), 2.84 (dd, J = 16.8, 11.2 Hz, 1 H), 2.53 (ddd, J = 16.6, 3.2, 1.2 Hz, 1 H). 13C NMR (100 MHz, CD3OD): δ = 173.45, 161.08, 126.21, 116.59, 107.98, 101.66, 52.14, 43.76, 36.71. HRMS-ESI: m/z [M – H] calcd for C9H7Br2N2O3: 348.8829; found: 350.8803.