The natural alkaloid isoanabasine: synthesis from 2,3′-bipyridine, efficient resolution with BINOL, and assignment of absolute configuration by Mosher’s method

A highly efficient and practical resolution of racemic 1-benzylisoanabasine, which was synthesized by reduction of the benzyl salt of 2,3′-bipyridine, has been achieved through molecular complexation with (R)-BINOL or (S)-BINOL to afford pure enantiomers (100% ee). The two enantiomers of the natural alkaloid isoanabasine have been obtained by debenzylation of the corresponding enantiomeric 1-benzylisoanabasine. Using Mosher’s method by NMR techniques, the absolute configuration of (−)-isoanabasine has been assigned as the (R)-configuration for the first time. Moreover, an unexpected rotamer ratio of Mosher’s amide was observed. The syn-form of two rotamers of (R)-MTPA-(R)-isoanabasine was predominant over the anti-form.

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(R)-1-Benzyl-3-(pyridin-2-yl)piperidineC17H20N2Ee = 100%[α]D20=-65.4 (c 2.0, ethanol)Source of chirality: resolutionAbsolute configuration: R

(R)-3-(Pyridin-2-yl)piperidineC10H14N2Ee = 100%[α]D20=-15.2 (c 1.0, ethanol)Source of chirality: chiral poolAbsolute configuration: R