3423-25-4Relevant articles and documents
Metabolism of N-alkyldiamines and N-alkylnortropinones by transformed root cultures of Nicotiana and Brugmansia
Boswell, Henry D.,Draeger, Birgit,Eagles, John,McClintock, Carol,Parr, Adrian,Portsteffen, Andreas,Robins, David J.,Robins, Richard J.,Walton, Nicholas J.,Wong, Chi
, p. 855 - 869 (2007/10/03)
A range of analogues of N-methylputrescine and tropinone were fed to transformed root cultures of Nicotiana rustica and/or a Brugmansia candida x aurea hybrid. These cultures were made by the transformation of the relevant plant species with Agrobacterium rhizogenes. A number of the metabolites, notably those showing a relatively modest alteration in the N-alkyl substituent, were metabolized in vivo to form homologues of the normal alkaloids biosynthesized by these roots. These products were identified by GC/MS and comparison with some synthetic reference materials. Analogues with major alterations in the size of the N-alkyl substituent were not metabolized at all. In the N. rustica cultures, the analogues fed at 1 mM significantly affected the profile of normal alkaloids, with up to a 4-fold diminution in nicotine being found in the presence of N-n-propylputrescine. The ratio between alkaloids of the pyrrolidine series and the piperideine series was also affected. In contrast, the presence of the analogues in the B. candida x aurea hybrid culture at 1 mM did not inhibit or substantially interfere with the accumulation of the normal spectrum of alkaloids. The potential for using these cultures to make complex novel products from simple precursors is discussed.
Conveniant Method for Replacement of Tertiary N-Methyl by Other Alkyl Groups: Application to Morphine Alkaloids
Manoharan, T. Samuel,Madyastha, K. Madhava,Singh, B. B.,Bhatnagar, S. P.,Weiss, Ulrich
, p. 5 - 11 (2007/10/02)
The replacement of N-methyl of N-methylpiperidine (1), 4-methylmorpholine (4), 2-methyl-1,2,3,4-tetrahydroisoquinoline (7) and tropine (10) by n-propyl, n-butyl and isopropyl groups (3a-3c, 6c, 9a-9c and 12a-12c) has been achieved in high yields by quaternization of the respective tertiary amine with appropriate alkyl halide and demethylation of the resulting quaternary salt with thiophenoxide.It has been established that demethylation is strongly favoured over the removal of n-propyl and n-butyl groups, whereas deisopropylation occurs to some extent.Surprisingly, in the case of 11c, deisopropylation predominates.This method has been applied to morphine (13b), codeine (13d) and thebaine (14b) for similar replacements.The rapid quaternization of thebaine (14b) has been assigned to the absence of H-14 in this alkaloid.The fact that quaternary salts of thebaine, which are susceptible to aromatization of the nucleus by extrusion of the ethanamine chain, are smoothly demethylated to N-alkylnorthebaines (18a-18c) in good yields indicates that demethylation, a bimolecular nucleophilic displacement, competes very successfully with elimination reaction.
