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Synthesis of Isobavachalcone and Some Organometallic Derivatives
Author(s) -
Grealis John P.,
MüllerBunz Helge,
Ortin Yannick,
Casey Michael,
McGlinchey Michael J.
Publication year - 2013
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201201063
Subject(s) - chemistry , benzaldehyde , chalcone , acetophenone , stille reaction , palladium , organic chemistry , stereochemistry , combinatorial chemistry , polymer , catalysis
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organometallic derivatives in which the 4‐(methoxymethoxy)benzaldehyde used in the Claisen–Schmidt condensation has been replaced by formylferrocene, formylruthenocene or (η 5 ‐formylcyclopentadienyl)(η 4 ‐tetraphenylcyclobutadiene)cobalt to form the corresponding analogues of isobavachalcone containing organometallic sandwich moieties.