| Popis: |
Locoweeds (Astragalus and Oxytropis spp.) continue to be a significant rangeland poisonous plant problem. The toxin in the plant has been identified as the polyhydroxy indoziline alkaloid names swainsonin. The overall reaction scheme is summarized. Initially, all reactions were conducted using swainsonine acetonide to enhance solubility in organic solvents and for protection of the hydroxyl groups. A number of N-alkylated derivatives of swainsonine could be produced by the reaction of swainsonine acetonide with 1,4-dibromo-2-butene and 1,4-diiodobutane. Alkyl addition on the nitrogen did occur, as evidenced by completed acetylation of the unprotected swainsonine derivatives (compounds 4 and 9) to give the corresponding triacetate compounds. Two possible isomers are produced, which are the cis and trans (relative to H-8a) adducts on the nitrogen, in a ratio of approximately 3:1. Both isomers were observed in LC/MS analysis of the product. Compounds 4 and 9 were reacted to yield multiple functional groups on the end of the alkyl chain, thus providing multiple chemistry options to be used later in conjugation with the carrier molecules. In general, the bromo derivatives were more reactive to a variety of functional groups than the iodo derivatives. However, the bromo reactions seemed reversible and the starting material was regenerated. The iodo derivative appeared to be more stable, but also less reactive towards OH and NH functional groups. N-iodobutane swainsonine did seem reactive towards SH groups as evidenced by the reaction with glutathione. |
