piperidines and decahydroquinoline-5-carboxylic-acid

A novel class of C

Topics: Acetylcholinesterase; Alkaloids; Cholinesterase Inhibitors; Huperzia; Lycopodium; Molecular Structure; Piperidines; Plant Extracts; Quinolines; Stereoisomerism

Approaches toward the syntheses of alkaloids belonging to the 2,6-disubstituted 3-hydroxypiperidine and cis-decahydroquinoline (cis-DHQ) classes of alkaloids are developed, starting from a common chiral nonracemic bicyclic lactam lactone (BLL). Two key δ-lactam intermediates, (5S,6S)-5-hydroxy-6-hydroxymethyl- and (5S,6S)-5-hydroxy-6-methylpiperidin-2-ones, are prepared; the latter δ-lactam is obtained via a direct decarbonylation of a bicyclic lactam lactol. The BLL is also used to prepare (4aR,5R,8aS)- and (4aR,5S,8aS)-5-methyloctahydroquinolin-2-ones, which involved a 6-exo-trig free-radical conjugate addition reaction. The stereoselectivity observed in the free-radical cyclization step is found to be governed by allylic 1,2-strain arising from the interaction of the N-(p-methoxybenzyl) group and the C6 substituent in the lactam ring of the free-radical intermediate. The effectiveness of the developed approaches is demonstrated by the asymmetric syntheses of (+)-2-epi-deoxoprosopinine, (-)-deoxoprosophylline, (+)-cis-195A, and 2,5-di-epi-cis-195A.

Topics: Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Cyclization; Lactams; Lactones; Molecular Structure; Piperidines; Quinolines; Quinolones; Stereoisomerism

A simple and efficient protocol for the construction of substituted piperazines, piperidines, thiomorpholines, decahydroquinolines, perhydrocyclopenta[b]pyridine, and pyrrolidines bearing N-hydroxy substituents through intramolecular reductive cyclization of diketoximes using sodium cyanoborohydride is described.

Topics: Borohydrides; Chemistry, Pharmaceutical; Cyclization; Molecular Structure; Morpholines; Oximes; Piperazines; Piperidines; Pyridines; Pyrrolidines; Quinolines; Stereoisomerism