Peptide heterocycle conjugates: A diverted Edman degradation protocol for the synthesis of N-terminal 2-iminohydantoins

Organic Letters

Volumn 5, Issue 8, 2003, Pages 1201-1204

  Evindar, Ghotas ^a   Batey, Robert A ^a  

^a UNIVERSITY OF TORONTO   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID DERIVATIVE; HYDANTOIN DERIVATIVE; ISOTHIOCYANIC ACID DERIVATIVE; NITROGEN; PEPTIDE; THIOUREA; AMIDE; IMINE; OLIGOPEPTIDE; THIOCYANIC ACID DERIVATIVE;

AMINO TERMINAL SEQUENCE; ARTICLE; CYCLIZATION; DEGRADATION; MOLECULAR DYNAMICS; SYNTHESIS; CHEMISTRY;

AMIDES; CYCLIZATION; HYDANTOINS; IMINES; OLIGOPEPTIDES; THIOCYANATES; THIOUREA;

EID: 0037587475     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol034032d     Document Type: Article

References (24)

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2. Following reviews give an overview of small biologically relevant heterocyclic pharmacophores: (a) Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96, 555-600. (b) Nefzi, A.; Ostresh, J. M.; Houghten, R. A. Chem. Rev. 1997, 97, 449-472. (c) Franzen, R. G. J. Comb. Chem. 2000, 2, 195-214.
3. Following reviews give an overview of small biologically relevant heterocyclic pharmacophores: (a) Thompson, L. A.; Ellman, J. A. Chem. Rev. 1996, 96, 555-600. (b) Nefzi, A.; Ostresh, J. M.; Houghten, R. A. Chem. Rev. 1997, 97, 449-472. (c) Franzen, R. G. J. Comb. Chem. 2000, 2, 195-214.
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21. Yu, Y.; Ostresh, J. M.; Houghten, R. A. J. Org. Chem. 2002, 67, 3138-3141. Houghten et al. recently demonstrated a resin-bound reaction in which Mukaiyama's reagent promotes the cyclization of an amide onto a thiourea group to form polymer-bound iminohydantoins, analogous to Scheme 3. This process was demonstrated using single amino acids coupled to p-methylbenzhydrylamine (MBHA) resin, providing the product 8 (or their tautomeric forms, 2-aminoimidazolidin-4-ones) following HF/anisole cleavage. See: Yu, Y.; Ostresh, J. M.; Houghten, R. A. Tetrahedron 2002, 58, 3349-3353.
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23. 2 (0.42 mmol), and the mixture was then stirred overnight. The reaction mixture was diluted with EtOAc (2.0 mL) and filtered through a prepacked Celite column, using EtOAc (4 mL) to remove the Amberlyst-A21 resin and HgS byproduct. The solution was added to the Celite column and allowed to sit on the column for 1 min before applying suction to the column.
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