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Intramolecular Opening of β‐Lactams with Amines as a Strategy Toward Enzymatically or Photochemically Triggered Activation of Lactenediyne Prodrugs
Author(s) -
Banfi Luca,
Guanti Giuseppe,
Rasparini Marcello
Publication year - 2003
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200390188
Subject(s) - chemistry , enediyne , intramolecular force , prodrug , moiety , lactam , ring (chemistry) , amine gas treating , stereochemistry , combinatorial chemistry , reactivity (psychology) , organic chemistry , biochemistry , medicine , alternative medicine , pathology
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)