CHAPTER 6
6 SIX-MEMBERED HETEROCYCLES
1. COMPOUNDS WITH ONE HETEROATOM
A. Pyridines
Agents that interact with cholinergic receptors have been extensively
investigated for the treatment of Alzheimer’s disease. Most of the
compounds discussed to this point bind at muscarinic sites. An alternate
approach involves administration of agents that bind to cholinergic
nicotinic receptors. A compound closely related structurally to nicotine
itself is currently being investigated in the clinic. The synthesis of this
agent starts with the dihalogenated pyridine ( 2 ) obtained from nicotine
( 1 ). Coupling of this with the monosilyl derivative from acetylene in the
presence of palladium: triphenyl phosphine and copper iodide replaces
iodine on the aromatic ring by the acetylene moiety 3. The chlorine on
the ring is then removed by reduction with zinc in acetic acid 4.
The silyl protecting group is then cleaved with fluoride ion to afford
altinicline( 5 ).^1
The Organic Chemistry of Drug Synthesis, Volume 7. By Daniel Lednicer
Copyright#2008 John Wiley & Sons, Inc.
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