Synthesis of Isobavachalcone and Some Organometallic Derivatives



Isobavachalcone [2′,4,4′-trihydroxy-3′-(3″-methyl-2″-butenyl)chalcone, 1] is a prenylated chalcone that has broad biological activity, in particular against neuroblastomas, the most common cancer in infancy. It is currently commercially available at a cost of $190/mg by extraction from Psoralea corylifolia and a number of other African and Asian plants. Several synthetic routes have been explored, and the most efficient procedure involves the palladium-catalysed Stille coupling of 3-iodo-2,4-bis(methoxymethoxy)acetophenone (25) with prenyltributyltin, Claisen–Schmidt condensation with 4-(methoxymethoxy)benzaldehyde to form the triply MOM-protected prenylchalcone 27 and finally deprotection with 2 M HCl in methanol to form isobavachalcone in an overall yield of 15 % over five steps. The X-ray crystal structures of 2,4-dihydroxy-3-iodoacetophenone (21) and of several prenylated chalcones are reported, including the elucidation of their hydrogen-bonding networks in the solid state. The synthetic route has been extended to include organometallic derivatives in which the 4-(methoxymethoxy)benzaldehyde used in the Claisen–Schmidt condensation has been replaced by formylferrocene, formylruthenocene or (η5-formylcyclopentadienyl)(η4-tetraphenylcyclobutadiene)cobalt to form the corresponding analogues of isobavachalcone containing organometallic sandwich moieties.