Stereoselective Syntheses of (+)-2-epi-Deoxoprosopinine, (-)-Deoxoprosophylline, (+)-cis-195A, and 2,5-Di-epi-cis-195A from a Common Chiral Nonracemic Building Block.
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.
Department of Chemistry and Biochemistry, University of Regina, Regina, Saskatchewan S4S 0A2, Canada.
Krishna
K
Annadi
Department of Chemistry and Biochemistry, University of Regina, Regina, Saskatchewan S4S 0A2, Canada.
Andrew G H
AG
Wee
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D007769:Lactams / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry*; D015363:Quinolones / Q000737:chemistry; D013237:Stereoisomerism
D000470:Alkaloids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007769:Lactams; D007783:Lactones; D010880:Piperidines; D011804:Quinolines; D015363:Quinolones; C445731:deoxoprosopinine; C062320:N-hydroxypiperidine; C037920:decahydroquinoline-5-carboxylic acid