Biosynthesis of lycopodine. Incorporation of Δ¹-piperideine and of pelletierine

Abstract

The biogenetic hypothesis that the Lycopodium alkaloids are modified dimers of pelletierine (2, 3) was tested experimentally in Lycopodiumtristachyum, Pelletierine is indeed incorporated into lycopodine, but only one pelletierine unit entered the alkaloid, rather than two units, as predicted. The hypothesis thus requires modification.Δ1-Piperideine serves as a specific precursor of lycopodine. Two Δ1-piperideine moieties are incorporated in such a way that the identity of C-2 and -6 of each of the precursor units is maintained.

Biosynthesis of Lycopodine. The Question of the Intermediacy of Piperidine-2-acetic Acid

“…Piperidine-2-acetoacetate (6) is postulated to arise by condensation of malonyl coenzyme A with piperidine-2-acetyl coenzyme A (4) and the latter, in turn, by addition of malonyl coenzyme A to A'-piperideine (3), an established intermediate in lycopodine biosynthesis (4,6).…”

“…of lycopodine, gave an inconclusive result. Piperidine-2-acetic acid or, more precisely, its coenzyme A ester (4), is postulated by the hypothesis to be a precursor of piperidine-2-acetoacetic acid (6), and should, like the latter, be incorporated into both 'halves' of lycopodine. It should serve as a source of the C, units, C-1 to -7 and C-9 to -15.…”

“…The salient features of this scheme are that pelletierine (7), the precursor of the C, chain, C-9 to -16, of lycopodine, is derived from piperidine-2-acetoacetate (6) in an irreversible decarboxylation, that the piperidine-2-acetoacetate (or its coenzyme A derivative (5)) is the precursor of the C, chain, C-1 to -8, of lycopodine, and that a CO, unit is expelled from the system at some stage after combination of piperidine-2-acetoacetate with pelletierine. Provided the steady state concentration of pelletierine is small compared to that of its postulated precursor, piperidine-2-acetoacetate, all experimental observations (1)(2)(3)(4)6) are accounted for by this hypothesis (6).…”

“…In the course of our studies of the biosynthesis of the Lycopodium alkaloids (1-6) it was found that acetate (2), lysine (1) (1, 2), cadaverine (2) (2, 6), A'-piperideine (3) (4,6), and pelletierine (7) (3, 4) serve as specific precursors of lycopodine (8). Activity from radioactively labelled samples of all these substrates is incorporated nonrandomly into the alkaloid.…”

The biosynthesis of the Lythraceae alkaloids. I. The lysine-derived fragment

“…refs. [7][8][9][10], and whose side chain originates from acetate (1 1-13). Biogenetically modelled syntheses of pelletierine have been reported (14).…”