Total Synthesis of the Pentacyclic Diterpenoid Tropone Hainanolidol

Abstract

The total synthesis of the unusual diterpenoid tropone, hainanolidol (1), discovered in the bark of the yew species, Cephalotaxus hainanensis, has been completed in 26 steps from 3,5-dimethylanisole. The intramolecular cyclopropanation reaction of the aryl ring in (30) by means of the rhodium mandelate-catalysed reaction of the diazoacetyl function was used to assemble the 5/7 ring system of (31), at the same time elaborating a cycloheptatriene moiety that could be transformed subsequently to the tropone functionality in the target molecule. While removing the acetal protecting group from (31) an unexpected Mukaiyama-type aldol process was induced by ZnBr2, affording (32), the structure of which was determined by X-ray analysis. With greater care, the aldehyde (33) could be obtained and the desired carbocyclic ring system completed by means of a base-catalysed aldol reaction with the newly formed hydroxyl being employed subsequently in the formation of the δ-lactone function in (35). Desilylation, reduction of the C-10 carbonyl function and brief exposure to acid finally afforded (1). This last step took advantage of the stability of the tropylium ion (40) to provide a 'thermodynamic sink' for the reaction outcome. The synthesis of (1) also constitutes a formal synthesis of the troponoid ether, harringtonolide (2), since this compound had been obtained previously from (1) by means of a transannular oxidation process. Methodology for the assembly of the tropone moiety in (1) and (2) was modelled on the simpler bi- and tricyclic systems, (13) and (22), respectively. Show more