Synthesis of the pentacyclic intermediate for dynemicin a and unusual formation of spiro-oxindole ring

✍ Scribed by Takaaki Okita; Minoru Isobe

• Publisher: Elsevier Science
• Year: 1994
• Tongue: French
• Weight: 755 KB
• Volume: 50
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(01)89417-5

✦ Synopsis

A pentacyclic compound was synthesized as an important intermediate of antitumor antibiotic dynemicins. The key step was the intramolecular Heck reaction using catalytic Pd reagent. During the course of the synthetic studies, an unusual Spiro ring compound was found to be produced via intramolecular conjugate addition. Dynemicin A (1) was isolated from the fermentation broth of Micromonospora chersinu and possesses potent cytotoxicity and in vivo antitumor activity. 2 This antibiotic is a hybrid of two typical chemotypes of antitumor agent, enediyne and anthraquinone. There are many synthetic3v4 and biological studies5 on the models including enediyne moiety. Mode of actions of enediyne unit is unveiling.5 On the other hand, this pentacyclic framework possessing anthraquinone is novel. Reports on synthesis of the anthraquinone part are few,6 including Schreibef s impressive worktb on methylated dynemicin A, and its role in the action of the drug is still unclear. In order to clarify the biological role of this pentacycles and also serve as an