Isolation, Characterization, and Synthesis of trans-Pilosine Stereoisomers Occurring in Nature. Circular Dichroism and Mass Spectral Studies

“Pilosine” of [α]²⁰+83.9° is shown to be a 1:1 mixture of pilosine and isopilosine. Data on pure pilosine are described. The isolation and assignment of structure of a new pilosine constituent in Pilocarpus jaborandi are herein presented. From circular dichroism measurements it is concluded that pilosine, isopilosine, and epiisopilosine are of 2R,3R,6S (1), 2S,3R,6S (4), and 2S,3R,6R configurations (3), respectively. Optimal conditions for the production of 3, 4, and the fluoro derivatives (3a and 3b), via aldol condensation between benzaldehyde, 2- and 4-fluorobenzaldehydes, and (3R)-pilosinine, in the presence of lithium methoxide, have been worked out. Effects of stereochemistry on trends of mass spectral fragmentations are discussed in terms of abundances of M- H₂O and m/e 223 ions being higher in the spectrum of the cis (1) than in that of the trans (4) isomer and in terms of [M - 1]/[M] ratios.