Synlett 2005(13): 2011-2014  
DOI: 10.1055/s-2005-871972
LETTER
© Georg Thieme Verlag Stuttgart · New York

Conjugation of Selenols with Aziridine-2-Carboxylic Acid-Containing Peptides

Nathan D. Ide, Danica P. Galonić, Wilfred A. van der Donk, David Y. Gin*
Department of Chemistry, University of Illinois, Urbana, IL 61801, USA
Fax: +1(217)2448024; e-Mail: gin@scs.uiuc.edu;
Further Information

Publication History

Received 19 May 2005
Publication Date:
20 July 2005 (online)

Abstract

The addition of PhSeH to aziridine-2-carboxylic acid containing peptides is described, thus expanding the scope of nucleophiles for the opening of this class of electrophilic peptide substrates. The process offers a new strategy for the generation of useful phenylselenocysteine derivatives and α-seleno-β-amino acid-containing peptides.

    References

  • 1a Marcaurelle LA. Bertozzi CR. Chem.-Eur. J.  1999,  5:  1384 
  • 1b Hang HC. Bertozzi CR. Acc. Chem. Res.  2001,  34:  727 
  • 1c Zhu Y. van der Donk WA. Org. Lett.  2001,  3:  1189 
  • 1d Cohen SB. Halcomb RL. J. Am. Chem. Soc.  2002,  124:  2534 
  • 1e Davis BG. Chem. Rev.  2002,  102:  579 
  • 1f Galonić DP. van der Donk WA. Gin DY. Chem.-Eur. J.  2003,  9:  5997 
  • 1g Liu H. Wang L. Brock A. Wong C.-H. Schultz PG. J. Am. Chem. Soc.  2003,  125:  1702 
  • 1h Galonić DP. van der Donk WA. Gin DY. J. Am. Chem. Soc.  2004,  126:  12712 
  • 1i Peri F. Nicotra F. Chem. Commun.  2004,  623 
  • 1j Zhu X. Schmidt RR. Chem.-Eur. J.  2004,  10:  875 
  • 1k Galonić DP. Ide ND. van der Donk WA. Gin DY. J. Am. Chem. Soc.  2005,  127:  7359 
  • 2 Korn A. Rudolph-Böhner S. Moroder L. Tetrahedron  1994,  50:  1717 
  • 3a Nakajima K. Takai F. Tanaka T. Okawa K. Bull. Chem. Soc. Jpn.  1978,  51:  1577 
  • 3b Nakajima K. Tanaka T. Morita K. Okawa K. Bull. Chem. Soc. Jpn.  1980,  53:  283 
  • 3c Tanaka T. Nakajima K. Okawa K. Bull. Chem. Soc. Jpn.  1980,  53:  1352 
  • 3d Okawa K. Nakajima K. Biopolymers  1981,  20:  1811 
  • 4 Van Leeuwen SH. Quaedflieg PJLM. Broxterman QB. Liskamp RMJ. Tetrahedron Lett.  2002,  43:  9203 
  • 5a Nakajima K. Tanaka T. Neya M. Okawa K. Bull. Chem. Soc. Jpn.  1982,  55:  3237 
  • 5b Okawa K. Nakajima K. Tanaka T. Neya M. Bull. Chem. Soc. Jpn.  1982,  55:  174 
  • 5c Kuyl-Yeheskiely E. Dreef-Tromp CM. van der Marel GA. van Boom JH. Recl. Trav. Chim. Pays-Bas  1989,  108:  314 
  • 7a Tanaka T. Nakajima K. Okawa K. Bull. Chem. Soc. Jpn.  1980,  53:  1352 
  • 7b Cardillo G. Gentilucci L. Tolomelli A. Chem. Commun.  1999,  167 
  • 7c Armaroli S. Cardillo G. Gentilucci L. Gianotti M. Tolomelli A. Org. Lett.  2000,  2:  1105 
  • 8a Hanessian S. Yang H. Schaum R. J. Am. Chem. Soc.  1996,  118:  2507 
  • 8b Hanessian S. Yang H. Tetrahedron Lett.  1997,  38:  3155 
  • 10a Okeley NM. Zhu Y. van der Donk WA. Org. Lett.  2000,  2:  3603 
  • 10b Gieselman MD. Zhu Y. Zhou H. Galonić D. van der Donk WA. ChemBioChem  2002,  3:  709 
  • 10c Zhu Y. Gieselman MD. Zhou H. Averin O. van der Donk WA. Org. Biomol. Chem.  2003,  1:  3304 
  • 10d Paul M. van der Donk WA. Mini-Reviews in Org. Chem.  2005,  2:  343 
6

A similar regioselectivity effect was also observed in the thiolysis of Azy-containing peptides. See ref. 1k.

9

The seleno-peptide conjugates 18 and 21 were directly isolated following cleavage from the resin, and were assessed to be >90% pure by 1H NMR.

11

Although solid-phase synthesis of Azy(3-Me)-containing peptides is a highly efficient process, attempts at on-bead selenolysis were not efficient due to competitive unproductive processes such as, inter alia, aziridine N-deacylation.

12

For detailed representative procedures on the solution-phase and solid-phase synthesis of aziridine-containing peptides, see ref. 1k.