Synthesis of Isocyano Peptides by Dehydration of the N-Formyl Derivatives

 

 Buy Article Permissions and Reprints All articles of this category

Abstract

Phosphoryl chloride in combination with triethylamine dehydrates N-formyl peptides to provide the corresponding iso­cyano peptides in excellent yields.

References

• 1 Isonitrile Chemistry   Ugi I. Academic Press Inc.; New York: 1971. 
  Google Scholar
• 2 Dömling A. Ugi I. Angew. Chem. Int. Ed.  2000,  39:  3168 
  CrossrefPubMedGoogle Scholar
• 3a Passerini M. Gazz. Chim. Ital.  1922,  52:  126 
  Google Scholar
• 3b Passerini M. Gazz. Chim. Ital.  1922,  52:  181 
  Google Scholar
• 4a Hoppe D. Angew. Chem., Int. Ed. Engl.  1974,  13:  789 
  CrossrefGoogle Scholar
• 4b Marcaccini S. Torroba T. Org. Prep. Proced. Int.  1993,  25:  141 
  CrossrefGoogle Scholar
• 5 Van Leusen D. Van Leusen AM. Org. React.  2001,  57:  417 
  Google Scholar
• 6 Nunami K.-I. Suzuki M. Matsumoto K. Yoneda N. Takiguchi K. Agric. Biol. Chem.  1984,  48:  1073 
  Google Scholar
• 7 Sakiyama F. Witkop B. J. Org. Chem.  1965,  30:  1905 
  Google Scholar
• 8 Creedon SM. Crowley HK. McCarthy DG. J. Chem. Soc., Perkin Trans 1  1998,  1015 
  CrossrefGoogle Scholar
• 9 Urban R. Marquarding D. Seidel P. Ugi I. Weinelt A. Chem. Ber.  1977,  110:  2012 
  Google Scholar
• For recent reviews on the isocyanide-based MCR, see:
• 10a Weber L. Curr. Med. Chem.  2002,  9:  2085 
  Google Scholar
• 10b Dömling A. Curr. Opin. Chem. Biol.  2002,  6:  306 
  Google Scholar
• 10c Hulme C. Gore V. Curr. Med. Chem.  2003,  10:  51 
  Google Scholar
• 10d Zhu J. Eur. J. Org. Chem.  2003,  1133 
  Google Scholar
• 11 For an application of isocyano dipeptides in the synthesis of cyclodepsipeptides, see: Zhao G. Sun X. Bienaymé H. Zhu J. J. Am. Chem. Soc.  2001,  123:  6700 
  CrossrefGoogle Scholar
• 12 Baldwin JE. O’Neil IA. Synlett  1990,  603 
  Article in Thieme ConnectGoogle Scholar
• POCl₃ in combination with a tertiary amine is a well-known dehydrating agent, see ref.1, and ref. 2. For the dehydration of α-formylamino acrylic acid to α-isocyano acrylic acid under mild conditions, see:
• 13a Schöllkopf U. Schröder R. Stafforst S. Liebigs Ann. Chem.  1974,  44 
  Article in Thieme ConnectGoogle Scholar
• 13b Nunami K.-I. Suzuki M. Yoneda N. Synthesis  1978,  840 
  Article in Thieme ConnectGoogle Scholar
• 14 Obrecht R. Herrmann R. Ugi I. Synthesis  1985,  400 
  Article in Thieme ConnectGoogle Scholar
• 16 Mazurkiewicz R. Synthesis  1992,  941 
  Article in Thieme ConnectGoogle Scholar
• Recent examples from our group:
• 17a González-Zamora E. Fayol A. Bois-Choussy M. Chiaroni A. Zhu J. Chem. Commun.  2001,  1684 
  CrossrefPubMedGoogle Scholar
• 17b Janvier P. Sun X. Bienaymé H. Zhu J. J. Am. Chem. Soc.  2002,  124:  2560 
  CrossrefPubMedGoogle Scholar
• 17c Gámez-Montaño R. Zhu J. Chem. Commun.  2002,  2448 
  CrossrefPubMedGoogle Scholar
• 17d Fayol A. Zhu J. Angew. Chem. Int. Ed.  2002,  41:  3633 
  CrossrefPubMedGoogle Scholar
• 17e Janvier P. Bienaymé H. Zhu J. Angew. Chem. Int. Ed.  2002,  41:  4291 
  CrossrefPubMedGoogle Scholar
• 17f Gámez-Montaño R. González-Zamora E. Potier P. Zhu J. Tetrahedron  2002,  58:  6351 
  CrossrefPubMedGoogle Scholar
• 17g Janvier P. Bois-Choussy M. Bienaymé H. Zhu J. Angew. Chem. Int. Ed.  2003,  42:  811 
  CrossrefPubMedGoogle Scholar

Compound 4: R_f = 0.43 (EtOAc/heptane = 1/1); [α]_D = +13.8 (c 0.3, CHCl₃). IR (CHCl₃): ν = 3422, 2138, 1744, 1684, 1603, 1522, 1497, 1437, 1363, 1180 cm^-1.
¹H NMR (250 MHz, CDCl₃, ppm): δ = 3.08-3.30 (m, 4 H), 3.69 (s, 3 H,), 4.37 (dd, J = 4.5 Hz, 7.3 Hz, 1 H), 4.84 (dt, J = 5.7 Hz, 7.8 Hz, 1 H), 6.73 (d, J = 5.7 Hz, 1 H), 7.20-7.33 (m, 10 H). ¹³C NMR (62.5 MHz, CDCl₃, ppm): δ = 37.6, 38.3, 52.4, 53.1, 59.4, 127.3, 127.6, 127.7, 129.6, 129.0, 134.4, 134.8, 164.1, 170.7. MS (EI): m/z = 336 (M⁺), 227, 245. Anal. Calcd for C₂₀H₂₀N₂O₃: C, 71.43; H, 5.95; N, 8.33. Found: C, 71.44; H, 5.98; N, 8.30. Compound 6: R_f = 0.48 (EtOAc/heptane = 1/1.5); [α]_D = +17.5 (c 0.5, CHCl₃). IR (CHCl₃): ν = 3421, 3012, 2138, 1745, 1685, 1603, 1521, 1497, 1455, 1362, 1210, 1280, 1120 cm^-1. ¹H NMR (250 MHz, CDCl₃, ppm): δ = 3.00-3.30 (m, 4 H), 3.72 (s, 3 H), 4.35 (dd, J = 4.2 Hz, 7.8 Hz, 1 H), 4.84 (dd, J = 6.7 Hz, 12.7 Hz, 1 H), 6.72 (d, J = 6.7 Hz, 1 H), 7.15-7.32 (m, 10 H). ¹³C NMR (62.5 MHz, CDCl₃, ppm): δ = 37.8, 38.9, 52.6, 53.6, 59.9, 127.5, 127.8, 128.8, 129.2, 129.5, 134.7, 135.2, 164.7, 170.9. MS (EI): m/z = 336 (M⁺), 277, 245. Anal. Calcd for C₂₀H₂₀N₂O₃: C, 71.43; H, 5.95; N, 8.33. Found: C, 69.92; H, 6.05; N, 8.15.