A series of 8'-substituted N-(endo-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamides were synthesized. The 5-HT4 receptor agonistic activity was evaluated using the isolated guinea pig ileum preparation. Of the compounds synthesized, N-(endo-8-(3-hydroxypropyl)-8-azabicyclo[3.2.1]oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (15a, TS-951) exhibi...

Libraries of 1-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones/oximes/O-methyloximes 1-14/15-28/29-42 and 7-methyl-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones/oximes/O-methyloximes 43-48/49-54/55-60 were synthesized and their stereochemistry was established by 1D/2D NMR spectral and single crystal XRD studies. All the synthesized oximes and oxime ethers were screened for their in vitro antimic...

Crystals of the title compound, C(15)H(17)NO(3), were obtained from a condensation reaction of 3-hydroxy-4-methoxybenzaldehyde with 1-azabicyclo[2.2.2]octan-3-one and subsequent crystallization of the product from methanol. The title compound, containing a double bond that connects the azabicyclic ring system to the 3-hydroxy-4-methoxybenzylidene group, was obtained with Z geometry.

Acid treatment of densely substituted 2-silyl-1,2-dihydropyridines provides a new and convenient entry to reactive azomethine ylides that can (1) be protonated and reduced with high stereoselectivity to give piperidines, (2) participate in [3 + 2] dipolar cycloaddition to give tropanes, and (3) undergo a Nazarov-like 6-π electrocyclization that upon reduction give 2-azabicyclo[3.1.0] systems.

As a first example of opening a secondary aziridine with a tertiary carbanion, the title amines (3a-c, aryl = phenyl, 4-tert-butylphenyl,2-naphthyl) were synthesized by opening N-(diphenylphosphinoyl)-7-azabicyclo[4.1.0]heptane, aziridine 1, with the corresponding alpha-potassium isopropylarenes, followed by a hydrolysis of the resulting phosphinamides 2a-c.

The first enantioselective total syntheses of virosaine A and bubbialidine are described. Key transformations include the formation of a tetracyclic intermediate via an intramolecular aza-Michael addition, generation of a N-hydroxy-pyrrolidine through a Cope elimination and an intramolecular [1,3]-dipolar cycloaddition to generate a complex 7-oxa-1-azabicyclo[3.2.1]octane ring system.

An enantiocontrolled synthesis pathway has been developed to provide formation of tricyclic amine 7, representing the ABC ring system of the complex alkaloid daphnicyclidin A (1). Our efforts describe preparation of the Z-hexahydro-(1H)-azocine 29 and cyclization to construct the novel 4-azabicyclo[5.3.2]dodecane 31. Transannular reductive amination following the deprotection of 31 gave the des...