Synthesis of a Tetrahydrofuranyl β-Amino Acid for Peptide Nucleic Acid Construction

Dedicated to Professor Steven Ley on the occasion of his 70^th birthday

Abstract

A tetrahydrofuranyl β-amino acid has been prepared by using the asymmetric dihydroxylation of a furyl alkene to establish the stereochemistry. The furan moiety was employed as a carboxylic acid surrogate.

Key words

amino acid - tetrahydrofuran - dihydroxylation - oxidation - furan

• References and Notes

• 1a Seebach D, Beck AK, Capone S, Deniau G, Groselj U, Zass E. Synthesis 2009; 1
• 1b Seebach D, Matthews JL. Chem. Commun. 1997; 2015
• 2a Cheng RP, Gellman SH, DeGrado WF. Chem. Rev. 2001; 101: 3219
• 2b Vasudev PG, Chatterjee S, Shamala N, Balaram P. Chem. Rev. 2011; 111: 657
• 2c Pandey SK, Jogdand GF, Oliveira JC. A, Mata RA, Rajamohanan PR, Ramana CV. Chem. Eur. J. 2011; 17: 12946
• 3a Vilaivan T. Acc. Chem. Res. 2015; 48: 1645
• 3b Sriwarom P, Padungros P, Vilaivan T. J. Org. Chem. 2015; 80: 7058 ; see also ref. 2c
• 4 Rjabovs V, Turks M. Tetrahedron 2013; 69: 10693
• 5 Hanessian S. Total Synthesis of Natural Products: The ‘Chiron’ Approach. Pergamon; Oxford: 1983
• 6 Kolb HC, VanNieuwenhze MS, Sharpless KB. Chem. Rev. 1994; 94: 2483
• 7a Harris JM, Keränen MD, Nguyen H, Young VG, O’Doherty GA. Carbohydr. Res. 2000; 328: 17
• 7b Takeuchi M, Taniguchi T, Ogasawara K. Synthesis 1999; 341
• 7c Harris JM, Keranen MD, O’Doherty GA. J. Org. Chem. 1999; 64: 2982
• 7d Kobayashi Y, Nakano M, Biju Kuamr G, Kishihara K. ­J. Org. Chem. 1998; 63: 7505
• 7e For the aminohydroxylation of vinylfurans, see: Bushey ML, Haukaas MH, O’Doherty GA. J. Org. Chem. 1999; 64: 2984
• 8a Julia M, Julia S, Guegan R. Bull. Soc. Chim. Fr. 1960; 1072
• 8b A one-pot Grignard addition and ring-opening substitution has been reported, see: Qi W, Wang P, Fan L, Zhang S. J. Org. Chem. 2013; 78: 5918
• 9 McCormick JP, Barton DL. J. Org. Chem. 1980; 45: 2566
• 10 Balme G, Fournet G, Gore J. Tetrahedron Lett. 1986; 27: 1907
• 11 Cheskis BA, Ivanova NM, Moiseenkov AM, Nefedov OM. Bull. Acad. Sci. USSR, Div. Chem. Sci. (Engl. Transl.) 1990; 39: 1839 ; Izv. Akad. Nauk SSSR, Ser. Khim. 1990, 2025
• 12 Sharpless KB, Amberg W, Youssef LB, Crispino GA, Hartung J, Jeong K.-S, Morikawa K, Wang Z.-M, Xu D, Zhang X.-L. J. Org. Chem. 1992; 57: 2768
• 13 Viaud MC, Rollin P. Synthesis 1990; 130
• 14a Mitsunobu O. Synthesis 1981; 1
• 14b Hughes DL. Org. Prep. Proced. Int. 1996; 28: 129
• 14c Simon C, Hosztafi S, Makleit S. J. Heterocycl. Chem. 1997; 34: 349
• 15 Details of the X-ray structure determination for compound 7 have been deposited with the Cambridge Crystallographic Database, CCDC-1408970. Copies of the data may be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (fax:[phone] or e-mail: [e-mail]).
• 16 Inversion is also shown by the change of J ₂,₃ in the ¹H NMR spectrum from 4 Hz in 6 to 8.4 Hz in 7.
• 17a Carlsen PH. J, Katsuki T, Martin VS, Sharpless KB. J. Org. Chem. 1981; 46: 3936
• 17b Plietker B. Synthesis 2005; 2453
• 17c Begliomini S, Sernissi L, Scarpi D, Occhiato EG. Eur. J. Org. Chem. 2014; 5448
• 18 (+)-(2S,3S)-3-[(9H-Fluoren-9-yl)(methoxy)(carbonyl)amino]-tetrahydrofuran-2-carboxylic Acid (1): Ruthenium trichloride hydrate (55 mg, 0.026 mmol) was added to a solution of sodium periodate (1.98 g, 9.33 mmol) in a mixture of EtOAc (1.5 mL), CH₃CN (2 mL) and H₂O (1 mL) at 0 °C. The mixture was stirred for 15 min, then carbamate 9 (0.5 g, 1.33 mmol) in the minimum of EtOAc was slowly added. The mixture was stirred for an additional 10 min, H₂O (10 mL) was added and the mixture was extracted with EtOAc (2 × 15 mL). The combined organic layers were washed with NaHCO₃ (20 mL) and acidified with 2 M HCl then extract with EtOAc (3 × 15 mL). The combined organic phase was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to give amino acid derivative 1 (85%, 400 mg) as a colourless solid. Mp 90–92 °C; [α]_D ²⁵ +40 (c 1.0, DMSO). IR (neat): 3332, 2924, 2854, 1720, 1535, 1450, 1095, 1049 cm^–1. ¹H NMR (500 MHz, DMSO-d ₆): δ = 1.80–1.81 (m, 1 H), 2.07–2.11 (m, 1 H), 3.89–3.91 (m, 2 H), 4.10 (d, J = 4.0 Hz, 1 H), 4.18–4.24 (m, 2 H), 4.34 (d, J = 6.5 Hz, 2 H), 7.32–7.35 (m, 2 H), 7.41–7.44 (m, 2 H), 7.70–7.77 (m, 3 H), 7.89 (d, J = 7.5 Hz, 2 H), 12.7 (br. s, 1 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 32.2, 47.1, 55.8, 65.8, 67.7, 81.4, 120.6, 125.6, 127.5, 128.1, 141.2, 144.3, 156.0, 173.2. MS (ESI⁺): m/z = 354.3 [M + H]⁺. HRMS: m/z [M + H]⁺ calcd. for C₂₀H₂₀NO₅: 354.1318; found: 354.1341.