ABSTRACT
The triple reuptake inhibitor GSK1360707F was synthesized via an efficient and scalable route that features an enyne cycloisomerization reaction catalyzed by either Pt(II) or Au(I). Key aspects of this work such as the choice of the nitrogen protecting group and initial enantioselectivity studies are discussed.
Subject(s)
Alkynes/chemistry , Neurotransmitter Uptake Inhibitors/chemistry , Neurotransmitter Uptake Inhibitors/pharmacology , Azabicyclo Compounds , Catalysis , Cyclization , Gold/chemistry , Heterocyclic Compounds, 2-Ring/chemical synthesis , Heterocyclic Compounds, 2-Ring/chemistry , Heterocyclic Compounds, 2-Ring/pharmacology , Isomerism , Magnetic Resonance Spectroscopy , Molecular Structure , Platinum/chemistry , StereoisomerismABSTRACT
[reaction: see text] An efficient synthetic route to the ABC tricyclic core of 1alpha-alkyldaphnanes has been developed. The conformational bias imparted by the C6-C9 oxo-bridge of BC-ring system 12 was used to elaborate the ABC-ring system precursor including the introduction of the beta-C5 hydroxyl group. A completely diastereoselective palladium-catalyzed enyne cyclization was then employed to establish the A-ring with a C1 appendage.
