Pyrrolizidine 1-methylene

Segall and coworkers described the in vitro mouse hepatic microsomal metabolism of the alkaloid senecionine (159) (Scheme 34). Several pyrrolizidine alkaloid metabolites were isolated from mouse liver microsomal incubation mixtures and identified (222, 223). Preparative-scale incubations with mouse liver microsomes enabled the isolation of metabolites for mass spectral and H-NMR analysis. Senecic acid (161) was identified by GC-MS comparison with authentic 161. A new metabolite, 19-hydroxysenecionine (160), gave a molecular ion consistent with the addition of one oxygen atom to the senecionine structure. The position to which the new oxygen atom had been added was made evident by the H-NMR spectrum. The three-proton doublet for the methyl group at position 19 of senecionine was absent in the NMR spectrum of the metabolite and was replaced by two signals (one proton each) at 3.99 and 3.61 ppm for a new carbinol methylene functional group. All other H-NMR spectral data were consistent for the structure of 160 as the new metabolite (222). 

Sodium hypochlorite reacts with (1) to give the 1-chloro derivative, which gives rise to a variety of products, including the bicyclic amine, pyrrolizidine, when treated with silver salts (72CJCH67). Quaternary salts derived from (3) react with sodium methoxide to give mostly the acyclic Hofmann elimination product (83%) minor amounts of (3) (14%) are also formed, together with a trace (2%) of the product of 5N2 attack on the a-methylene carbon (80JOC3952). 

Trapping of the a-cation by active methylene compounds or enol ethers has been applied to the synthesis of some alkaloids having the skeletons of pyrrolizidine, indo-lizidine, and quinolizidine 21 -23. ... 

Heliotrine (161) Small Gram-ve coccus 7 a-Hydroxy-1 -methylene-8a-pyrrolizidine (173) (-) 165... 

Europine (165) Peptococcus heliotrinreducans (7a-Hydroxy-l-methylene-8a-pyrrolizidine) (173) (-) 166... 

CsHisN l-Methylene-Sa-pyrrolizidine Occurs free as the base bp 120°/170 mm -43.1 d... 

In last year s Report, reference was made to the discovery of three examples of a new type of pyrrolizidine alkaloid containing the dihydropyrrolizinone ring system. Two closely related acyl-pyrroles have now been detected in aerial parts of Kleinia kleinioides (Sch. Bip.) M. R. F. Taylor by Bohlmann and Knoll. Spectral data on the first pyrrole showed it to be an isomer of senaetnine (29), with different stereochemistry at C-7, C-12, or C-13. Lack of material prevented clarification of the stereochemistry of isosenaetnine (29). The second new compound differed from isosenaetnine in replacement of one methyl group by methylene, and it is therefore formulated as dehydroisosenaetnine (30). The stereochemistry is again uncertain. 

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