Fredericamycin antitumor agent

W.H. Moser and co-workers developed a new and efficient method for the stereocontrolled construction of spirocyclic compounds, including the spirocyclic core of the antitumor agent fredericamycin The strategy involved a one-pot aldol additioniBrook rearrangement cyclization sequence beginning from arene chromium tricarbonyl complexes and can formally be described as a [3+2] annulation. 

Domino reduction/aldol cydization was applied for the synthesis of ( )-fredericamydn A 44, a potent antitumor and antibiotic agent, by Kelly et al. [18] in 1988 (Scheme 9.10). DIBAL-H (diisobutylaluminum hydride) reduction of lactone 45 afforded an intermediate 46 having both enolate and aldehyde. Subsequent cychzation via aldol reaction gave a diastereomeric mixture of spiro hydroxy ketone 47, which was further converted into ( )-fredericamycin A 44 by sequential organic transformations. A similar strategy was employed by Mehta et al. [19] for the synthesis of bicyclo[3.3.1]nonan-9-one core of hyperforin, an antidepressant. 

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