Reactivity of 4-tert-butyldimethylsiloxy-1,2,3,6-tetrahydropyridines with hydrazines.

Influence of lipophilicity on the interactions of N-alkyl-4-phenyl-1,2,3,6-tetrahydropyridines and their positively charged N-alkyl-4-phenylpyridinium metabolites with cytochrome P450 2D6.

The relationship between lipophilicity and CYP2D6 affinity of cyclic tertiary (N-alkyl-4-phenyl-1,2,3,6-tetrahydropyridines) and quaternary (N-alkyl-4-phenylpyridinium) amines was examined. The 1,2,3,6-tetrahydropyridine scaffold was chosen due to its common occurrence in the structures of CYP2D6 ligands such as the Parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and...

Switch in regioselectivity of epoxide ring-opening by changing the organometallic reagent.

The regio- and stereoselective ring-opening of a 2-(2'-oxiranyl)-1,2,3,6-tetrahydropyridine using organometallic reagents is reported. The choice of the organometallic reagent determines the formation of either 2-[(R)-1-hydroxyalkyl]- or 2-[(S)-2-hydroxy-1-alkyl]-1,2,3,6-tetrahydropyridines. The formation of 2-[(S)-2-hydroxy-1-alkyl]-1,2,3,6-tetrahydropyridines is a rare example of epoxide ring...

Synthesis and mechanistic studies on the monoamine oxidase (MAO) catalyzed oxidation of 1,4-disubstituted-1,2,3,6- tetrahydropyridines

Nucleophilic addition to 2,3-disubstituted butanal derivatives and their application to natural product synthesis.

The reaction of 2,3-anti-2-tert-butyldimethylsiloxy-3-substituted butanal derivative [anti-B, (±)-10 and (±)-16] derived from trans-(2,3)-epoxy butanoate (1) with carbon nucleophiles [α-furyl anion, acetate anion, and indium (In)-assisted allyl anion] has been investigated to give selectively the anti-, anti-adduct D. This anti-stereoselection could be explained by the Felkin-Anh transition sta...

Importance of monoamine oxidase A in the bioactivation of neurotoxic analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a potent dopaminergic neurotoxin that causes biochemical, pharmacological, and pathological deficits in experimental animals similar to those seen in human parkinsonian patients. All of the deficits can be prevented by treating mice with selective inhibitors of monoamine oxidase B (MAO-B), including deprenyl, prior to MPTP administration. W...