Due to their restricted conformational flexibility, cyclic peptides are of great interest in connection with structure-activity relationships, especially the elucidation of bioactive conformations. For linear peptides that do not contain turn structure-inducing amino acid residues, the cyclization reaction may be an inherently improbable or slow process, and side reactions, such as cyclodimerization and epimerization at the C-terminal residue, may dominate. A number of 1-hydroxy-7-azabenzotriazole-based onium salts were examined for cyclization of thymopentin-derived pentapeptides and the results compared with data from more conventional coupling reagents. The azabenzotriazol-derived coupling reagents stood out as being the most effective by far. The cyclizations proceed extremely rapidly, and in contrast to other coupling reagents, C-terminal epimerization was generally less than 10%. C-terminal D-amino acid residues favor the formation of monocyclic pentapeptide rings. A similar effect was observed for cyclization of linear N-methylamino acid-containing peptides, suggesting that reversible amide bond alkylation such as Hmb-modification should be useful in promoting the cyclization of pepitdes devoid of turn-inducing amino acid residues.

Azoethane intermediate: N,N ′‐ Diethylsulfamide product: Azoethane solvent: petroleum ether intermediate: N,N ′‐dicyclohexylsulfamide intermediate: N,N ′‐dispiro(cyclohexane‐1,9′‐fluorene)‐4‐ylsulfamide product: n ‐C 3 H 7 product: n ‐C 4 H 9 product: tert ‐C 4 H 9 product: cyclo ‐C 6 H 11 product: 4‐NO 2 ‐C 6 H 4

No abstract

3,3‐Pentamethylen‐oxaziridin 5, das als Isomeres des Cyclohexanon‐oxims für eine neue Synthese des Caprolactams Interesse besitzt, wird aus Cyclohexanon mit Ammoniak und Hypochlorit in 73proz. Ausbeute hergestellt, aus Cyclohexanon mit Chloraminlösung in 85proz. Ausbeute. Ein kristallines 1:1‐Addukt von Chloramin an Cyclohexanon 7 läßt sich in 91proz. Ausbeute zu 5 cyclisieren.

Der Vilsmeier‐Komplex aus Phosgen und Dimethylformamid liefert mit 4‐Picolin (I) die Verbindung (II).