Synlett, Table of Contents Synlett 2013; 24(7): 886-888DOI: 10.1055/s-0032-1317802 letter © Georg Thieme Verlag Stuttgart · New York A Synthesis of (–)-cis-2-Aminomethylcyclopropanecarboxylic Acid [(–)-CAMP] Masato Oikawa* Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan Fax: +81(45)7872403 Email: moikawa@yokohama-cu.ac.jp , Yuka Sugeno Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan Fax: +81(45)7872403 Email: moikawa@yokohama-cu.ac.jp , Yuichi Ishikawa Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan Fax: +81(45)7872403 Email: moikawa@yokohama-cu.ac.jp , Hideyuki Tukada Yokohama City University, Seto 22-2, Kanazawa-ku, Yokohama 236-0027, Japan Fax: +81(45)7872403 Email: moikawa@yokohama-cu.ac.jp › Author Affiliations Recommend Article Abstract Buy Article All articles of this category Abstract An enantioselective synthesis of (–)-cis-2-aminomethylcyclopropanecarboxylic acid [(–)-CAMP] has been achieved in 2.5% total yield over ten steps starting from 2-furaldehyde. The synthesis features diastereoselective cyclopropane formation via diazene, followed by oxime formation and the reduction, for construction of the γ-aminobutyric acid (GABA) motif. Key words Key wordsamino acids - cycloaddition - photochemistry - ring contraction - stereoselective synthesis Full Text References References and Notes 1a Johnston GA. R. Curr. Top. Med. Chem. 2002; 2: 903 1b Ordóñez M, Cativiela C. Tetrahedron: Asymmetry 2007; 18: 3 1c Silverman RB. Angew. Chem. Int. Ed. 2008; 47: 3500 1d Levandovskiy IA, Sharapa DI, Shamota TV, Rodionov VN, Shubina TE. Future Med. Chem. 2011; 3: 223 2 Allan RD, Curtis DR, Headley PM, Johnston GA. R, Lodge D, Twitchin B. J. Neurochem. 1980; 34: 652 3 Duke RK, Chebib M, Balcar VJ, Allan RD, Mewett KN, Johnston GA. R. J. Neurochem. 2000; 75: 2602 4 Galeazzi R, Mobbili G, Orena M. Tetrahedron: Asymmetry 1997; 8: 133 5 Duke RK, Allan RD, Chebib M, Greenwood JR, Johnston GA. R. Tetrahedron: Asymmetry 1998; 9: 2533 6 Baxendale IR, Ernst M, Krahnert W.-R, Ley SV. Synlett 2002; 1641 7 Rodríguez-Soria V, Quintero L, Sartillo-Piscil F. Tetrahedron 2008; 64: 2750 8 Rispens MT, Keller E, de Lange B, Zijlstra RW. J, Feringa BL. Tetrahedron: Asymmetry 1994; 5: 607 9 Moradei OM, Paquette LA. Org. Synth. 2003; 80: 66 10 Spectroscopic data for diazene 4: [α]D 20.1 –57.2 (c = 0.94, CHCl3). 1H NMR (400 MHz, C6D6): δ = 5.05 (d, J = 6.8 Hz, 1 H), 4.41 (d, J = 2.0 Hz, 1 H), 3.95 (m, 1 H), 3.79 (m, 1 H), 3.35 (td, J = 10.6, 4.3 Hz, 1 H), 2.34 (m, 1 H), 1.95 (m, 1 H), 1.70 (m, 1 H), 1.52–1.57 (m, 2 H), 1.25 (m, 1 H), 1.10 (br, 1 H), 0.99–1.01 (m, 6 H), 0.85–0.95 (m, 4 H), 0.69–0.79 (m, 2 H). 13C NMR (100 MHz, C6D6): δ = 167.0, 104.3, 93.5, 83.1, 77.7, 48.1, 39.9, 39.1, 34.3, 31.3, 25.7, 23.2, 22.3, 21.0, 15.9. 11 Spectroscopic data for cyclopropane 2: [α]D 20.3 +137.0 (c = 1.07, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 5.41 (s, 1 H), 3.53 (td, J = 10.8, 4.11 Hz, 1 H), 2.01–2.19 (m, 4 H), 1.61–1.66 (m, 2 H), 1.37 (m, 1 H), 1.15–1.25 (m, 2 H), 0.77–1.04 (m, 13 H). 13C NMR (100 MHz, CDCl3): δ = 175.4, 99.8, 77.5, 47.7, 40.2, 34.2, 31.4, 25.3, 23.1 (2 ×), 22.1, 20.9, 17.1, 15.6, 11.8. 12 Gannett PM, Nagel DL, Reilly PJ, Lawson T, Sharpe J, Toth B. J. Org. Chem. 1988; 53: 1064 13a Ueda M, Miyabe H, Sugino H, Miyata O, Naito T. Angew. Chem. Int. Ed. 2005; 44: 6190 13b Sukhorukov AY, Ioffe SL. Chem. Rev. 2011; 111: 5004 14 A suspension of protected CAMP 9 (13.0 mg, 0.053 mmol) in hydrochloric acid (6 M, 0.200 mL) was stirred at 90 °C for 8 h. The reaction mixture was then concentrated under reduced pressure and subjected to ion-exchange chromatography (Dowex 1-X8, 1.0 × 5 cm, H2O) to give (–)-CAMP hydrochloride (8.2 mg, 100%) as a colorless solid; [α]D 20.3 –35.9 (c = 0.50, H2O). IR (KBr): 3430, 3105, 1706, 1600, 1428, 1194, 861 cm–1. 1H NMR (400 MHz, D2O): δ = 3.08–3.19 (m, 2 H), 1.80 (m 1 H), 1.53 (m, 1 H), 1.20 (m, 1 H), 0.94 (m, 1 H). 13C NMR (100 MHz, D2O): δ = 176.5, 37.9, 17.7, 17.4, 12.8.
