Mechanism and synthesis of pharmacologically active quinolones from Morita–Baylis–Hillman adducts

The synthesis of quinolones from Morita–Baylis–Hillman (MBH) adducts is reported. The quinolone skeleton is formed via a TFA-mediated cyclization of the MBH adduct, and a mechanism study using ESI(+)-MS(/MS) has indicated the role played by TFA in this key reaction step. The total syntheses of Norfloxacin and a benzyl quinolone carboxylic acid (BQCA) derivative are described. Norfloxacin is a fluoroquinolonic antibacterial drug whereas BQCA is M1 receptor positive allosteric modulator and seem to provide access to new potential drugs for Alzheimer disease, pain, and sleep disorders. The syntheses of these two important quinolones exemplify the versatility and potentiality of the approach.

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