Synthesis of Isobavachalcone and Some Organometallic Derivatives

Abstract

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organometallic derivatives in which the 4‐(methoxymethoxy)benzaldehyde used in the Claisen–Schmidt condensation has been replaced by formylferrocene, formylruthenocene or (η5‐formylcyclopentadienyl)(η4‐tetraphenylcyclobutadiene)cobalt to form the corresponding analogues of isobavachalcone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.

Enantiodivergent Synthesis of Axially Chiral Biphenyls from σ‐Symmetric 1,1'‐Biphenyl‐2,6‐diol Derivatives by Single Lipase‐Catalyzed Acylative and Hydrolytic Desymmetrization

“…2'‐Bromo‐2,6‐dimethoxy‐1,1'‐biphenyl (6a): Compound 6a was synthesized from 1,3‐dimethoxybenene and 1‐bromo‐2‐chlorobenzene 4a according to the reported procedure . Its 1 H NMR data ([D 6 ]DMSO) are in good agreement with those reported . 1 H NMR (500 MHz, CDCl 3 ) δ = 7.66 (dd, J = 8.0, 1.0 Hz, 1H), 7.33–7.37 (m, 2H), 7.18–7.24 (m, 2H), 6.66 (d, J = 8.0 Hz, 2H), 3.74 (s, 6H).…”

“…Preparation of Substrates 1 and 3: The preparation of 1 and 3 were performed as shown in Scheme . 1,3‐Bis(methoxymethyl)benzene was prepared according to the reported procedure . Other chemicals were purchased and used as received.…”

“…1,3-Bis(methoxymethyl)benzene was prepared according to the reported procedure. [16] Other chemicals were purchased and used as received. Scheme 1. 2′-Bromo-2,6-dimethoxy-1,1′-biphenyl (6a): Compound 6a was synthesized from 1,3-dimethoxybenene and 1-bromo-2-chlorobenzene 4a according to the reported procedure.…”

“…[17] Its 1 H NMR data ([D 6 ]DMSO) are in good agreement with those reported. [16] 1 H NMR (500 MHz, CDCl 3 ) δ = 7.66 (dd, J = 8.0, 1.0 Hz, 1H), 7.33-7.37 (m, 2H), 7.18-7.24 (m, 2H), 6.66 (d, J = 8.0 Hz, 2H), 3.74 (s, 6H).…”

Synthesis and characterization of organometallic chalcones functionalized with a crown ether fragment. Spectroscopic and electrochemical behavior

“…">Synthesis of the organometallic chalcones 2-3.The compounds were synthesized following a procedure similar to that described for ferrocenyl and cymantrenyl chalcone derivatives. 11,16 It is based on the Claisen-Schmidt reaction involving the condensation of the organometallic ketones 1a-c and the corresponding crown ether or organic aldehydes Id-e (Scheme 1). Derivatives 2a-c and 3awere obtained by reaction of the corresponding precursors in the presence of NaOH and were dissolved in water/ethanol mixed solvent for greater solubility of the components.…”