Solid phase synthesis of 'head-to-tail' cyclic peptides using a sulfonamide 'safety-catch' linker: The cleavage by cyclization approach

Tetrahedron Letters

Volumn 40, Issue 47, 1999, Pages 8197-8200

  Yang, Lihu ^a   Morriello, Greg ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Combinatorial chemistry; Cyclization; Peptides; Polypeptides; Solid phase synthesis

Indexed keywords

AMIDE; CYCLOPEPTIDE; PEPTIDE; SULFONAMIDE; TRITYL DERIVATIVE;

ARTICLE; CYCLIZATION; DRUG SYNTHESIS; SOLID;

EID: 0033584984     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(99)01701-3     Document Type: Article

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22. Purchased from Calbiochem-Novabiochem Corp, loading 1 mmol/g.
23. Typical procedure: (a) After the completion of the linear peptide synthesis, the resin (200 mg) was treated with DIEA (6 equiv.) and trityl chloride (3.5 equiv.) overnight while agitated. The resin was drained and washed with DCM (×5) and NMP. (b) The resin was treated with DIEA (10 equiv.) and iodoacetonitrile (10 equiv.) in NMP and agitated at room temperature overnight. The resin was drained and washed with NMP (×4) and DCM (×4). (c) Add 2 mL of a stock solution of 3% TFA, 5% TIS, 92% DCM. The mixture was agitated at room temperature for 2 h. The resin was drained and washed with DCM (2×10 mL), THF (2×10 mL), and 1% DIEA/THF (1×3 mL). (d) Immediately to the resin was added 2 mL THF and 38 μ1 DIEA (3 equiv.) and agitated overnight. The solution was collected and the resin washed with THF, and the combined solution was concentrate to dryness. The residue was purified by a short silica gel column, removing both polar and non-polar impurities, (e) The protected cyclic peptide was treated with 2 mL of a solution of 95% TFA, 2.5% water, 2.5% TIS for 4 h. The solution was then concentrated to dryness and precipitated with ether.
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25. The results will be reported elsewhere.