Efficient Synthetic Route to Ravidosamine Derivatives

Abstracts

Concise synthesis of ravidosamine, the amino sugar constituent of ravidomycin and other antibiotics, has been achieved. The key steps include (1) regioselective reduction of benzylidene acetal with DIBAL, and (2) stereoselective reduction of oxime to the corresponding amine by using samarium diiodide in the ­presence of methanol.

Key words

ravidosamine - regioselectivity - boron trifluoride etherate - stereoselectivity - samarium diiodide - amino sugar

References

• 1a Nicolaou KC. Mitchell HJ. Angew. Chem. Int. Ed.  2001,  40:  1576 
• 1b Nicolaou KC. Boddy CNC. Bräse S. Winssinger N. Angew. Chem. Int. Ed.  1999,  38:  2096 
• 1c Weymouth-Wilson AC. Nat. Prod. Rep.  1997,  14:  99 
• 2 Hauser FM. Ellenberger SR. Chem. Rev.  1986,  86:  35 
• 3 Findlay JA. Liu J.-S. Radics L. Rakhit S. Can. J. Chem.  1981,  59:  3018 
• 4 Futagami S. Ohashi Y. Imura K. Hosoya T. Ohmori K. Matsumoto T. Suzuki K. Tetrahedron Lett.  2000,  41:  1063 
• 5 Ben A. Yamauchi T. Matsumoto T. Suzuki K. Synlett  2004,  225 
• 6 Arai M. Tomoda H. Matsumoto M. Takahashi Y. Woodruff BH. Ishiguro N. Kobayashi S. Omura S. J. Antibiot.  2001,  54:  554 
• 7a Itoh T. Kinoshita M. Aoki S. Kobayashi M. J. Nat. Prod.  2003,  66:  1373 
• 7b

  The absolute stereostructure of the sugar portion of komodoquinone A has not been established.

• 8 Binkley RW. Goewey GS. Johnston JC. J. Org. Chem.  1984,  49:  992 
• 9 Lindhorst TK. Thiem J. Liebigs Ann. Chem.  1990,  1237 
• 10 Guo and coworkers studied exactly the same system, noting qualitatively the difference in the reactivities of 8 and 9 for DIBAL reduction and also suggested the solution by employing BF₃·OEt₂. Unfortunately, the exact conclusion could not be drawn from their data, because they used the α/β-anomeric mixture of methyl glycoside. See: Guo Z.-W. Deng S.-T. Hui Y.-Z. J. Carbohydr. Chem.   1996.  15:  p.965 
• 11 Bundle DR. Josephson S. Can. J. Chem.  1978,  56:  2686 
• 12 Gauthier DR. Szumigala RH. Armstrong JD. Volante RP. Tetrahedron Lett.  2001,  42:  7011 
• 14 Frigerio M. Santagostino M. Tetrahedron Lett.  1994,  35:  8019 
• 15 Brünker H.-G. Adam W. J. Am. Chem. Soc.  1995,  117:  3976 
• 16 Yamaura M. Noguchi M. Umemura K. Yoshimura J. Kidorui  1993,  22:  54 
• 17 Molander GA. Org. React.  1994,  46:  211 
• 19 Alper PB. Hung S.-C. Wong C.-H. Tetrahedron Lett.  1996,  37:  6029 

13

To a stirred solution of 9 (356 mg, 1 mmol) in CH₂Cl₂ (5 mL) at 0 °C was added BF₃·OEt₂ (0.25 mL, 2 mmol). After stirring for 5 min, the reaction was quenched with sat. aq NaHCO₃ solution. The mixture was extracted with CH₂Cl₂, and the combined organic extracts were washed with brine, dried over Na₂SO₄, filtered, and concentrated. The ¹H NMR indicated that the ratio of 8 and 9 was about 2:1.

18

Compound 18: ¹H NMR (400 MHz, CDCl₃): δ = 7.40-7.26 (m, 10 H), 4.86 (d, J = 11.2 Hz, 1 H), 4.78 (d, J = 3.7 Hz, 1 H), 4.64-4.56 (m, 3 H), 4.07 (dd, J = 3.7, 11.2 Hz, 1 H), 3.85 (br q, J = 6.6 Hz, 1 H), 3.62 (br d, J = 2.9 Hz, 1 H), 3.33 (s, 3 H), 3.00 (dd, J = 2.9, 11.2 Hz, 1 H), 2.59 (s, 6 H), 1.13 (d, J = 6.6 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 138.2 (C), 138.1 (C), 128.2 (CH), 128.1 (CH), 128.0 (CH), 127.9 (CH), 127.5 (CH), 127.4 (CH), 97.2 (CH), 82.9 (CH), 75.2 (CH₂), 75.1 (CH), 71.1 (CH₂), 66.8 (CH), 61.4 (CH), 54.9 (CH₃), 43.5 (CH₃), 16.3 (CH₃). IR (neat): 3030, 2931, 2895, 1454, 1099, 1053, 733, 696 cm^-1.