Lactam ring closure

The use of carbodiimides as mediators in biological condensation reactions is of considerable importance. Sheehan received a Nobel price for the first total synthesis of phe-noxymethyl penicillin using DCC to effect the /3-lactam ring closure reaction. Diiso-propylcarbodiimide was used two years later to achieve the ring closure reaction in the... 

DCC is also used to prereact carboxyl groups with 0-benzylhydroxylamine prior to /8-lactam ring closure. A water soluble carbodiimide in combination with HOBt is used in several steps of the total synthesis of nisin, a pentacyclic polypeptide. Carbodiimides are also used for amide bond formation in the synthesis of the antiviral antibiotic distamycin Similarly, carbodiimides are used in the synthesis of a model depsipeptide lactone related to quinoxaline antibiotics. In the last synthesis, DCC in the presence of pyridine is used in the depsipeptide bond formation. 

Penam derivatives with different C-2 and C-3 substituents were synthesized by the group at Astra Lakemedel Co. [19,20] (14) using a new /3-lactam ring-closure, but they do not report any activity data either. 

The first step of the reaction is apparently a diaza-Cope rearrangement, followed by tautomer-ization and lactam ring closure. 

Without additional reagents Lactam ring closure... 

Decarboxylative acylation—Lactam ring closure with N-dealkylation s. 17, 898... 

N-Dealkylation, lactam ring closure with — 17, 898 O-Dealkylation (s. a. Ethers, cleavage)... 

Acetic anhydride Lactam ring closure with N-deaikylation... 

---