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Solid-phase synthesis of peptide–heterocycle hybrids containing a tripeptide-derived 6,6-fused bicyclic subunit

✍ Scribed by Wayne D Kohn; Lianshan Zhang


Book ID
104230824
Publisher
Elsevier Science
Year
2001
Tongue
French
Weight
104 KB
Volume
42
Category
Article
ISSN
0040-4039

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✦ Synopsis


The solid-phase synthesis of peptides incorporating a tripeptide-derived 6,6-fused bicyclic subunit is described. The bicyclic moiety (3,8,10-trisubstituted 2,9-dioxo-5-thia-1,8-diazabicyclo[4.4.0]decane) can be incorporated anywhere in a peptide sequence and is formed spontaneously upon TFA cleavage through condensation of an aldehyde with a backbone amide nitrogen and side-chain thiol, resulting in a thiazinone ring. The reaction is regio-and stereoselective and also allows for the incorporation of the bicyclic moiety, which may represent a constrained b-turn mimic, into a macrocyclic peptide.