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Synlett 2009(5): 833-837  
DOI: 10.1055/s-0028-1087949
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

The Application of tert-Butanesulfinamide in the Asymmetric Synthesis of the Core Structure of Polyoxin and Nikkomycin Antibiotics

Yong-Chun Luo, Huan-Huan Zhang, Peng-Fei Xu*
State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, P. R. of China
Fax: +86(931)8915557; e-Mail: xupf@lzu.edu.cn;
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Publication History

Received 11 October 2008
Publication Date:
24 February 2009 (online)

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Abstract

A stereoselective approach to the core structure of polyoxin and nikkomycin antibiotics has been developed. The key steps of this approach include diastereoselective nucleophilic addition of 2-lithiofuran to tert-butanesulfinyl imine derived from (S)-tert-­butanesulfinamide and ribosyl aldehyde for the generation of C-5 stereocenter, and the use of triflic acid to remove tert-butylsulfonyl group. Significantly, the synthesis provides a method for large-scale preparation of polyoxin and nikkomycin analogues because of simple operation, excellent yield and high stereoselectivity.

Key words

polyoxin - nikkomycin - (S)-tert-butanesulfinamide - ­ribose - asymmetric synthesis

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Procedure for the Synthesis of Compound 4: To a solution of n-BuLi (2.164 M in hexane, 1.39 mL, 3.0 mmol) at -78 ˚C was added a solution of furan (245 mg, 3.6 mmol) in THF (5 mL), and the mixture was stirred at r.t. for 3 h. The mixture was then cooled to -78 ˚C, and a solution of tert-butanesulfinyl imine 2 (0.5 M in THF, 4.0 mL, 2.0 mmol) was added via syringe over 10 min. The reaction mixture was stirred at -78 ˚C for 3 h and quenched with a sat. NH4Cl solution (2 mL). The solvent was evaporated under reduced pressure and the residue was treated with H2O (10 mL). The mixture was extracted with EtOAc, dried over anhyd Na2SO4 and concentrated. Flash chromatography of the residue (petroleum ether-EtOAc, 6:1) afforded compound 4 (96%) as a white solid; mp 81-82 ˚C; [α]D ²0 +3 (c = 0.5, CH2Cl2). IR (KBr): 3235, 2935, 1462, 1377, 1210, 1157, 1092 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 7.42 (d, J = 0.8 Hz, 1 H), 6.37 (d, J = 2.8 Hz, 1 H), 6.34 (dd, J = 2.0, 3.2 Hz, 1 H), 4.95 (d, J = 6.0 Hz, 1 H), 4.93 (s, 1 H), 4.63 (d, J = 6.0 Hz, 1 H), 4.43 (s, 1 H), 4.42 (d, J = 3.6 Hz, 1 H), 3.71 (dd,
J = 2.0, 5.4 Hz, 1 H), 3.21 (s, 3 H), 1.49 (s, 3 H), 1.33 (s, 3 H), 1.23 (s, 9 H). ¹³C NMR (100 MHz, CDCl3): δ = 152.5, 142.5, 112.6, 110.4, 109.9, 108.7, 88.1, 85.0, 82.1, 77.2, 56.7, 56.6, 55.6, 26.5, 25.1, 22.7. HRMS: m/z [M + H+] calcd for C17H28NO6S: 374.1632; found: 374.1636.

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Crystal data for 4 has been deposited at the Cambridge Crystallographic Data Centre with the deposition number 701981. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.com.

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Spectroscopic Data of Compound 14: [α]D ²0 +16 (c = 0.98, CHCl3). IR (KBr): 3299, 3065, 1750, 1696, 1239 cm-¹. ¹H NMR (400 MHz, CDCl3): δ = 9.09 (br s, 1 H), 7.30 (m, 5 H), 7.05 (s, 1 H), 5.94 (d, J = 5.2 Hz, 1 H), 5.93 (d, J = 8.8 Hz, 1 H), 5.53 (t, J = 5.6 Hz, 1 H), 5.28 (t, J = 6.0 Hz, 1 H), 5.10 (d, J = 4.0 Hz, 2 H), 4.84 (d, J = 3.9 Hz, 1 H), 4.38 (t, J = 4.4 Hz, 1 H), 3.80 (s, 3 H), 2.09 (s, 6 H), 1.88 (s, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 169.6, 169.5, 169.3, 163.3, 156.0, 135.8, 135.5, 128.5, 128.3, 128.1, 112.0, 87.5, 81.9, 77.2, 72.3, 69.7, 67.4, 60.3, 55.1, 52.9, 20.3, 12.4. HRMS: m/z [M + NH4 +] calcd for C24H31N4O11: 551.1989; found: 551.1984.