Intramolecular Opening of β-Lactams with Amines as a Strategy Toward Enzymatically or Photochemically Triggered Activation of Lactenediyne Prodrugs

✍ Scribed by Luca Banfi; Giuseppe Guanti; Marcello Rasparini

• Publisher: John Wiley and Sons
• Year: 2003
• Tongue: English
• Weight: 315 KB
• Volume: 2003
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/ejoc.200390188

✦ Synopsis

Abstract

In order to develop a general strategy for selective activation of designed enediyne prodrugs belonging to the “lactenediyne” family, we studied the scope of intramolecular transamidation of simple monocyclic β‐lactams bearing a tethered amine. The effect of substituents, of reaction media, and of the type of tether, on the rate of transamidation is disclosed. The possibility of triggering the transamidation event under mild conditions by the action of suitable enzymes or UV light was demonstrated on model monocyclic β‐lactams. Finally, the strategy of intramolecular opening of the β‐lactam leading to a larger seven‐membered ring was employed on a lactenediyne, demonstrating that ring enlargement could unleash the reactivity of the enediyne moiety. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)