5- hygroline

In the few years since the chapter on the pyrrolidine alkaloids was written they have not been the subject of much additional work. The recent investigations to be described relate to hygrine, hygroline, cuscohygrine, stachydrine, betonicine, and turicine. The structure of carpaine has also been fully elucidated, and this alkaloid has been shown to be a piperidine and not a pyrrolidine alkaloid and hence will be described under the heading The P3addine Alkaloids.  

Hygroline has been synthesized by the catalytic reduction of Z-hygrine. 

The reduction product consists of a mixtiu of i-hygroline and -pseudo-hygroline which are separated by the fractional crystallization of their piorates. The base liberated from the more soluble picrate is converted to the benzoyl derivative and further purified by repeated crystallization of its chlorplatinate. Synthetic l-hygrohne melts at 34 and has 

Recently, cuscohygrine has been detected in the fresh roots of Atropa belladonna L., and also by paper chromatography in Datura stramonium L. (4). The alkaloid (XXV) had been synthesized by 

Spath and Tuppy (5), but the synthesis involved the dry distillation of a salt of (.V-methyl-a-pyrryl)-acetic add. The same synthesis was also reported by Rapoport and Jorgensen (6). A more convincing synthesis has since been described (2). It consists of the partial reduction of. V-methyl-a-pyrrolidone with LiAlH4 followed by the condensation of the resulting amino-aldehyde with acetonedicarboxylic acid. There is formed a mixture of hygrine and cuscohygrine. 

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Two reviews on pyrrolidine alkaloids have appeared in volumes I (7) and VI (2) of this series. At that time, the only alkaloids mentioned were hygrine (1), hygroline (2), cuscohygrine (3), stachydrine (4), and betonicine (5). Carpaine,... 

Hygrine (1) and hygroline (2) were known compounds when the first reviews on pyrrolidine alkaloids in this series were written. Since 1950, the configurations of 1 and 2 have been determined and new sources of the alkaloids have been found. 

New sources of hygrine are the roots of Nicandra physaloides (L.) Gaertn. (Solanaceae) (9, JO), Dendrobium chrysanthum Wall. (Orchidaceae) (11), and Cochlearia arctica Slecht (Cruciferae) (12). Hygroline was also isolated from this latter source as well as from Carallia brachiata (Lour.) Merr. (Rhi-zophoraceae), a plant from eastern Asia, New Guinea, and Queensland (13), and... 

Gynotroches axillaris Bl. (Rhizophoraceae—Queensland) (14). Reference 11 contains the first reported H NMR and mass spectra of hygroline. 

Electrochemistry offers a new and promising alternative for the generation of masked iminium ions. This approach is illustrated by the elegant syntheses of hygrine and hygroline (Scheme 22) (168). 

Scheme 22. Electrochemical syntheses of hygrine and hygroline. (a) HOCH2CH2OH, H (b) LiAIR, (c) H 96% overall.

O eOCHj Li [A1H4]/Ethcr Ruckil. 10 min 2-( 2-Hydroxy-propyl)-/-methyI-pyrrolidin [4 Diastereoisomere Hygrolin (2 Isomcre) + Pseudo-hygrolin (2 Isomcre)] 81 6... 

The 7r-facial selectivity of cycloadditions between (Z)-13 and the five-mem-bered cyclic nitrone 194 was slightly lower (de 64%). The pyrrolidine natural compound (-)-hygroline was obtained from the major adduct, exo(t)-202 [159b]. Both exo and rr-facial selectivities decreased in reactions with vinyl sulfoxides of (E)-configuration. The stereochemical results obtained from (Z)-13 were explained by assuming the exo approach of the dipole to the less hindered face of the dipolarophile 13 which adopts conformation A depicted in Scheme 96, with the lone electron pair at sulfur in an s-cis arrangement. This explana-... 

Trace quantities of (+ )-hygroline were obtained from the bark 100). 

This oxidation of hygroline to optically inactive hygrine characterizes the former as l-methyl-2-(/3-hydroxypropyl)-pyrrolidine (the alcohol of dZ-hygrine). 

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