Synthesis of a tricyclic lactone embodying the ABC-ring system of stephaoxocanidine, by tin(IV) chloride-assisted sulfonamidoacetal cyclization and an aromatization promoted by triethylamine
Darío A. Bianchi and Teodoro S. Kaufman*
Instituto de Química Orgánica de Síntesis (IQUIOS, CONICET-UNR) and
Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario,
Suipacha 531, (S2002LRK) Rosario, Argentina
E-mail:
[email protected]
Dedicated to Professor Edmundo A. Rúveda on the occasion of his 70th birthday and to Professor Roberto A. Rossi on occasion of his 60th birthday
(received 30 Jun 03; accepted 25 Aug 03; published on the web 26 Aug 03)
Abstract
The synthesis of the polysubstituted 8-oxa-1-azaphenalene lactone 4, which embodies the ABC- ring system of stephaoxocanidine, a tetracyclic isoquinoline alkaloid recently isolated from the tubers of Stephania cepharantha Hayata, is reported. Elaboration of 4 was carried out by means of the camphorsulfonic acid-assisted lactonization of 9, coupled to a titanium(IV) chloride- mediated acetal cyclization of the resulting lactone 10 to form the tricyclic intermediate 12, followed by the base-promoted aromatization of the latter to 13 and final benzylic bromination. Lactone 4 constitutes an advanced key intermediate for the total synthesis of stephaoxocanidine, the simplest stephaoxocane.
Keywords: Stephaoxocanidine, natural products, synthesis, isoquinolines, cyclization
Introduction
The stephaoxocanes constitute a new, small family of isoquinoline alkaloids sharing the tetracyclic stephaoxocane1 skeleton (1a). This family, which was independently uncovered during the past decade by Japanese,1 Chinese2 and Brazilian3 research groups, has only five members (1b-1f), all of which have been isolated from Menispermaceæ employed in folk medicine.4 The structurally simplest stephaoxocane is stephaoxocanidine (1b), a Stephania cepharantha Hayata alkaloid which contains a fully unsaturated isoquinoline ring system like eletefine (1c), isolated from Cissampelos glaberrima (also known as Cissampelos pareira).
