A diverse array of biologically active, lipid-soluble alkaloids have been discovered in amphibian skin. Such alkaloids include the following: the steroidal samandarines from salamanders, the batrachotoxins, histrionicotoxins, gephyrotoxins, and epibatidine from neotropical poison frogs (Dendrobatidae), the pumiliotoxins, allopumiliotoxins, homopumiliotoxins, and decahydroquinolines from certain...

The rates of reaction with nitrous acid of four methylsubstituted piperidines to form the corresponding Nnitrosopiperidines were compared with that of piperidine. The relative rates for piperidine, 2-methyl-, 2,6-dimethyl-, and 2,2,6,6-tetramethyl-piperidine were approximately 100:20:10:1, showing considerable steric hindrance tp nitrosation by the «methyl groups. The rate of formation of nitr...

2-(2-Cyano-2-phenylethyl)aziridines were converted into novel cis- and trans-2-chloromethyl-4-phenylpiperidine-4-carbonitriles via alkylation with 1-bromo-2-chloroethane followed by microwave-assisted 6-exo-tet cyclization and regiospecific ring opening. The latter piperidines were used as eligible substrates for the synthesis of stereodefined 2-chloromethyl-, 2-hydroxymethyl-, and 2-carboxymet...

Single-nitrogen containing saturated cyclic amines are an important part of both natural and synthetic bioactive compounds. A number of methodologies have been developed for the synthesis of aziridines, azetidines, pyrrolidines, piperidines, azepanes and azocanes. This review highlights some facile and green synthetic routes for the synthesis of unsubstituted, multisubstituted and highly functi...

A practical and highly stereoselective approach to access 2,6-disubstituted piperidines using an amidine auxiliary is reported. Following the diastereoselective addition of Grignard reagents at the 2-position of an activated pyridinium salt, the amidine group directs a regioselective metalation at the 6-position, enabling further functionalization. A subsequent electrophilic quench or a Negishi...

Dwoskin et al. (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S.C. 154(b) by 238 days.

A new method for one-pot synthesis of 2,3-substituted piperidine from N-PMP aldimine and aqueous glutaraldehyde via formal [4+2] cycloaddition is reported. This reaction involves organocatalytic direct Mannich reaction-reductive cyclization with high yields (up to 90%) and excellent enantioselectivities (up to >99%). The practicability of this method is also shown at a gram scale as well as thr...

The synthesis and monoamine transporter activity of additional members of a series of 3,4-disubstituted piperidines (truncated analogues of the WIN series) are described. All members of this series were prepared from arecoline hydrobromide in optically pure form and were evaluated for their ability to inhibit high affinity uptake of dopamine (DA), serotonin (5-HT) and norepinephrine (NE) into r...