Ammonium pyrrolizidine alkaloids

In a series of papers, Segal 1 and co-workers described various HPLC methods for the analysis of pyrrolizidine alkaloids in plant material. A cyano-type column in combination with tetrahydrofuran - 0.01 M ammonium carbonate was used (Fig.3.3) for the isolation and identification of some senecio alkaloids11,13 13,3 . A gradient of 13% tetrahydrofuran, increasing to 26%, gave good separations. Similar results could be obtained with an isocratic system containing 16% tetrahydrofuran. 

Reductive cyclization has been used in a novel, recent synthesis of the alkaloids ( )-isoretronecanol (22) and ( )-trachelanthamidine (23) by Borch and Ho. Condensation of the dianion derived from methyl acetoacetate with Z-l,4-dichlorobut-2-ene, followed by cyclization with sodium meth-oxide yielded the cycloheptenone ester intermediate (32) (Scheme 2). Reductive amination of this ketoester with sodium cyanoborohydride and ammonium nitrate gave a mixture of the diastereoisomeric aminoesters 33 and 34. Oxidation with osmium tetroxide and periodate, followed by reductive cyclization, again using sodium cyanoborohydride, gave the two pyrrolizidine esters 35 and 36 in a ratio of 1 2 [gas-liquid chromatography (GLC) analysis]. The esters were separated by preparative layer chromatography, and lithium aluminum hydride reduction of the individual esters gave the two pyrrolizidine alkaloids 22 and 23. 

The saturated pyrrolizidine bases, which are nontoxic even when esterified as in the natural alkaloids, have been used by Kuzovkov et cd. (243, 244) to synthesize diquaternary ammonium salts with curare-like properties. 

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