RuO 4-mediated oxidative polycyclization of linear polyenes. A new approach to the synthesis of the bis-THF diol core of antitumour cis–cis adjacent bis-THF annonaceous acetogenins

Abstract

The RuO 4-catalyzed oxidative polycyclization of some selected linear polyenes, possessing a repetitive 1,5-diene structural motif, has been investigated. The all- trans triene ( E, E, E)-acetic acid henicosa-2,6,10-trienyl ester gave the expected bis-tetrahydrofuranyl diol product possessing a threo- cis- threo- cis- threo relative configuration, along with a mixture of the corresponding bis-THF ketols. These compounds can be seen as useful intermediates in the synthesis of the bis-THF diol core of adjacent bis-THF antitumour acetogenins possessing a threo- cis- threo- cis- erythro relative configuration, such as rolliniastatiin-1, membranacin, rollimembrin and membrarollin. Oxidation of the related all- trans tetraene ( E, E, E, E)-acetic acid pentacosa-2,6,10,14-tetraenyl ester stops at the second cyclization step giving a mixture of a threo- cis- threo- cis- threo bis-THF diol and the corresponding ketol products. Oxidation of the triene ( E, Z, E)-acetic acid 12-acetoxy-dodeca-2,6,10-trienyl ester stops at the monocyclization level failing to give bis-cyclized products, as previously observed for the related isoprenoid triene ( E, Z)-farnesyl acetate. This result confirms the difficulty of closing a second THF ring when the central double bond of the triene possesses a cis configuration. Based on the collected results, a plausible model is proposed that both explains the observed cis/trans stereoselectivity for each ring-closing step in these processes, and rationalize the stereochemical course of the previously studied polycyclization of the isoprenoid polyenes ( E, E)-farnesyl acetate, geranylgeranyl acetate and squalene.