Isotopically labelled tropane alkaloids. The synthesis of (RS)‐[3′, 3′‐²H₂]‐ and (RS)‐[1′‐¹³C, 3′, 3′‐²H₂]‐ hyoscyamines for metabolism studies in plants

Abstract

(2b) hyoscyamines, involving the reaction between phenylacetyl tropine and formaldehyde is described. The isotopically labelled products enable the metabolism of hyoscyamine to be studied in plants such as Datura stramonium.

Syntheses of deuterium labelled atropine and scopolamine

“…The disappearance of the 3H signal at 2.14 ppm indicates the complete labelling of the N-methyl group in good agreement with the published NMR data. 9 The mass spectrum of the [ Surprisingly, we did not found any description of deuterium labelled scopolamine synthesis in the literature. However, and from acetylnorscopolamine.…”

“…9 Unfortunately, these methods are not suitable for our purpose for the following reasons: long multistep syntheses [2][3][4][5][6][7] or labelling on the tropic acid moiety. 3,9 Noratropine 3, the first intermediate needed, has been prepared in various ways: partial synthesis from nortropine, 10 demethylation of atropine by reaction with trichloroethyl chloroformate followed by treatment with zinc dust in acetic acid, 11 oxidative demethylation of atropine with potassium permanganate with low yield, 12,13 photochemical demethylation of atropine 14,15 and iron salt mediated Polonovski demethylation of atropine N-oxide. 16 We decided to prepare noratropine 3 by demethylation of atropine with a-chloroethyl chloroformate because this reagent is known to give high yields of demethylated products and the cleavage of the carbamate intermediate 2 is done by simply heating it in methanol.…”