Synthesis of Furan- and Benzofuran-Containing Drugs

The syntheses of several commercially available furan and benzofuran based pharamaceutics have been published. The examples below are meant to illustrate some of the more general methods employed in the synthesis of these important compounds. Note that the majority of the syntheses highlighted below take advantage of preformed or readily available furan or benzofuran derivatives. 

Dantrolene is a muscle relaxant that is currently the only effective treatment for malignant hyperthermia, a rare and life-threatening disorder that can be triggered by general anesthesia in some patients. Dantrolene has been synthesized by a number of different routes starting from readily available furaldehyde and its derivatives. 

The original synthesis of dantrolene by Snyder and co-workers (shown below) employed a Meerwein arylation to produce the corresponding 5-aryl-2-fliraldehyde intermediate. Condensation of this intermediate with 1-aminohydantoin under acidic conditions produced the target compound dantrolene. 

Suzuki and co-workers recently applied a Stille coupling reaction to synthesize dantrolene and several of its congeners. Coupling of 4-nitro iodide with 5-(tri-butylstannyl)-2-furaldehyde in the presence of dichloro-palladium(II) triphenylphosphine gave the corresponding 5-p-nitrophenyl-2-fliraldehyde in 75% yield. Condensation with 1-aminohydantoin produced the desired dantrolene in 94% yield (71% yield over two steps). 

Ceftin is a second-generation broad-spectrum cephalosporin antibiotic used to treat bacterial infections resulting in Lyme s disease, bronchitis, sinusitis, tonsillitis, otitis, skin infections, gonorrhea, and urinary tract infections, and it is considered the antibiotic of choice for otitis media. Ceftin functions by inhibiting bacteria cell wall biosynthesis. 

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