The Configuration of (+)‐8‐Ethylnorlobelol‐I; a Correction of the Literature

Abstract

The piperidine alkaloid (+)-8-ethylnorlobelo-I is assigned the revised 2S,8S absolute configuration as depicted in 7. LiAl(O-tBu)3H reduction of the ketone rac-5 proceeded with a high stereoselectivity to give, after hydrolysis of the carbamate function, the s y n amino alcohol rac-6. Inversion of the C-8 configuration of ent-6 yielded (-)-8-ethylnorlobelol-I ent-7. A short nitrone-alkene-based synthesis of rac-7 has been developed.

A New Synthesis of All Four Stereoisomers of 2-(2,3-Dihydroxypropyl)piperidine via Iterative Asymmetric Dihydroxylation To Cause Enantiomeric Enhancement. Application to Asymmetric Synthesis of Naturally Occurring Piperidine-Related Alkaloids

“…Both the melting point (mp 88−89 °C) and the specific rotation {[α] D +25.8° (EtOH)} are almost identical with those reported (vide supra) . It is thus concluded that the absolute configuration of natural (+)-8-ethylnorlobelol-I is 2 S -(2 S ) …”

History, chemistry and biology of alkaloids from Lobelia inflata

“…Thus, for many years, the absolute configuration was accepted as that described by Schöpf. Recently, Hootelé et al 30 questioned this assignment and correctly revised the absolute configuration to (2S,8S). This assertion of Hootelé was confirmed, a short time later, by Takahata's group, 31 with the first asymmetric total synthesis of (C)-20.…”

Alkaloids of Andrachne aspera

“…(+)-Allosedridine, 9,10 (-)-8-epi-8-ethylnorlobelol I (4), and (-)-8-epihalosaline (7) were also isolated from A. aspera. As the homologue derivatives 4 and 7 were difficult to separate, their mixture was treated with methyl chloroformate, and the two corresponding carbamates were obtained as pure compounds.…”

“…Andrachcinine (1): oil, [R] 22 D -108°(c 2.5, CHCl 3 ); IR (CHCl 3 ) ν max 3335, 1715 cm -1 ; 1 H NMR (CDCl 3 , 250 MHz) δ 5.78 (1H, m, H-4), 5.61 (1H, m, H-3), 3.79 (1H, m, H-8), 3.56 (1H, m, H-2eq), 3.14 (1H, tt, J ) 11, 3.5 Hz, H-6ax), 2.59 and 2.81 (2H, 2 dd, J ) 16, 7 Hz, CH 2 -CO), 2.43 and 2.46 (2H, 2m, CH 2 -CO), 2.31 (3H, s, N-CH 3 ), 1.95 (1H, m, H-5), 1.28-1.75 (8H, m), 1.06 (3H, t, J ) 7 Hz, CH 3 ), 0.92 (3H, t, J ) 7 Hz, CH 3 ); 13 (7), 212 (8) 5) from (-)-8-Epihalosaline (7). Andrachcinidine (5) was obtained from (-)-8-epihalosaline by the procedure described for the synthesis of related compounds.…”

“…(-)-8-epi-8-Ethylnorlobelol I ( 4) and (-)-8-Epihalosaline (7). The mixture of 4 and 7 (13.4 mg) from A. aspera was treated with methyl chloroformate (0.03 mL) in a 2% aqueous K 2 CO 3 solution (5 mL).…”