Efficient enantiomeric synthesis of pyrrolidine and piperidine alkaloids from tobacco.
An enantiomeric synthesis of six piperidine and pyrrolidine alkaloids, (S)-nornicotine 1, (S)-nicotine 2, (S)-anatabine 3, (S)-N-methylanatabine 4, (S)-anabasine 5, and (S)-N-methylanabasine 6, known as natural products in tobacco, was established from a common chiral homoallylic (S)-3-(1-azido-but-3-enyl)-pyridine 15. An intramolecular hydroboration-cycloalkylation of the homoallylic azide intermediate 15 served as the key step in the pyrrolidine ring formation. A ring closing metathesis reaction (RCM) of a diethylenic amine intermediate (S)-allyl-(1-pyridin-3-yl-but-3-enyl)-carbamic acid benzyl ester 20 served as the key step in the piperidine ring formation. From the commercially available 3-pyridinecarboxaldehyde 13, a short and convenient enantiomeric synthesis of tobacco alkaloids is described: (S)-nornicotine 1 (5 steps, with an overall yield of 70%), (S)-nicotine 2 (6 steps, 65%), (S)-anatabine 3 (8 steps, 30%), (S)-N-methylanatabine 4 (8 steps, 25%), (S)-anabasine 5 (8 steps, 35%), and (S)-N-methylanabasine 6 (8 steps, 25%).
Felpin
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FX
Laboratoire de Synthèse Organique, CNRS UMR 6513, Faculté des Sciences et des Techniques, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
Girard
S
S
Vo-Thanh
G
G
Robins
R J
RJ
Villiéras
J
J
Lebreton
J
J
D000470:Alkaloids / Q000138:chemical synthesis* / Q000302:isolation & purification; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D010880:Piperidines / Q000737:chemistry* / Q000302:isolation & purification; D010947:Plants, Toxic; D011759:Pyrrolidines / Q000737:chemistry* / Q000302:isolation & purification; D014026:Nicotiana / Q000737:chemistry*
D000470:Alkaloids; D010880:Piperidines; D011759:Pyrrolidines; C032727:piperidine; C032519:pyrrolidine