Synthesis of Two Fluoro Analogues of the Nicotinic Acetylcholine Receptor Agonist UB-165

Abstract

Two racemic fluoropyridine analogues 4 and 5 of the potent nicotinic agonist UB-165 have been synthesized. Halogenated pyridines 7 and 12 provided the organometallic reagents needed for the Negishi and Suzuki coupling reactions used for the preparation of 4 and 5, and the N-vinyloxycarbonyl protecting group of 8 and 15 was cleaved using a novel trifluoroacetic acid-mediated deprotection protocol. Analogue 4 retained high binding affinity at rat brain alpha4beta2 and alpha7 nicotinic receptors.

SnCl2·2H2O as a precatalyst in MCR: synthesis of pyridine derivatives via a 4-component reaction in water

“…coenzyme vitamin B 6 family and numerous alkaloids) and biologically active compounds. 7 Several elegant and effective methods have been reported for the synthesis of pyridine derivatives 8 including MCRs. 9 For example, in 2012 we reported the synthesis of pyridine derivatives via a montmorillonite K-10 catalyzed 4-component reaction of β-ketoester, arylaldehyde, malononitrile and an alcohol.…”

Nicotinic Agonists, Antagonists, and Modulators From Natural Sources

“…13, as exemplified by U-165 (Wright et al, 1997;Sharples et al, 2002;Karig et al, 2003;Sutherland et al, 2003). The laevorotatory enantiomer (−)-U-165 had a 14-fold higher affinity for α 4 β 2 receptors than the dextro-rotatory enantiomer (+)-U-165.…”

Fluorinated Natural Products with Clinical Significance

“…Fluorinated derivatives of aminoglycosides [21], huperazine [22], frontalin [23], epibatidine [24], and daunorubucin [25] are just a few examples that could be examined within such a discourse. Further, there are numerous examples of fluorinated steroids [26], prostaglandins [27], vitamins [28] and antibiotics [29] that will also be omitted.…”