Loline structure

The simple necine bases loline (18), norloline (19), and lolinine (20) have been identified previously from Lolium cuneatum Nevski.7 Further investigations on the seeds of this plant by Russian workers have established the presence of four new alkaloids. N-Formylnorloline (21),8 JV-methyl-loline (22), JV-acetylnorloline (23), and AT-formyl-loline (24)9 have been identified. In addition, a novel dimeric pyrrolizidine alkaloid, lolidine, containing chlorine, was isolated in trace amounts (7 mg from 10 kg of seeds). The structure (25) has been suggested for lolidine on the basis of spectral data.10... 

The structure (25) has been deduced for both loline, an alkaloid of Lolium cuneatum Nevski, ° and festucine, a constituent of Festuca arundinacea Schreb. The identity of loline and festucine has now been confirmed by direct comparison. 

A number of closely related naturally occurring pyrrolizidine cyclic ethers have been identified.74 Four of these, loline (=festucine75) (119), norloline (120), lolinine (121), and decorticasine (122), have had their structures and relative configurations established by chemical methods. In addition, the relative stereochemistry of loline has been defined by an X-ray crystal structure determination of its dihydrochloride.76 The absolute configurations for all these alkaloid bases have now been established by the X-ray technique of anomalous dispersion using the same dihydrochloride of loline (119).7 7... 

The structures for loline (CLXXXVIa), lolinine (CLXXXVIb), and norloline (CLXXXVIc) follow from reaetions which are shown in Chart... 

Loline ( = festucine 34), norloline (35), lolinine (36), and decorticasine (37) form a quartet of closely related alkaloids whose structures and relative configurations have been established by interconversions, particularly with loline, for which the relative configuration expressed in (34) has been established by A"-ray crystal structure determination of its dihydrochloride. The absolute configurations for these bases implied in the structures [(34)—(37)] have now been established by the X-ray technique of anomalous dispersion, using the dihydrochloride of loline. 

A toxic variety (Gl-43) of this grass yielded perloline and festucine C8H14ON2, dihydrochloride (mp 242° [a] f +4.6°) which is isomeric with loline. Its chemical reactions are reminiscent of those of the latter and its structure (XXXVII) is consistent with all spectral data and not inconsistent with its chemical reactions, none of which, however, appear to be critical ones (92). 

A later publication (151) reported further experimental work, all of which could be interpreted on the basis of structure LVIII for norloline. Loline would then be the A-methyl derivative and lolinine the iV-acetyl derivative of the latter. These structures, however, failed to account for the apparent stability of the system > C(OR)NH2 and a reexamination of the problem prompted a revision to structures based upon LIX for norloline (152). 

Early work on Lolium alkaloids (10, 11), on Adenocarpus alkaloids (23-26), and on Festuca alkaloids (18, 21) relied heavily on chemical reactions and interconversions. By 1960, Yunusov and Akramov (14) had reported deme-thylation of loline (3) to norloline (4), methylation of loline to N-methylloline (8), acetylation to JV-acetylloline (6), and conversion to a hydroxychloro derivative. Yates and Tookey (18) prepared the same compound (cleavage of the C(2)-C(7) ether linkage using HCl) but the complete structure of this hydroxychloro derivative (17) was only recently elucidated (22). Preparation of 17 was achieved from 3 by the action of concentrated HCl in a sealed tube for several hours at 160°. In mild base 17 is relatively unstable and reverts to... 

Figure 4.5. Loline Derivatives Structure-Activity Relationship Between Straight N-acyl Chain Length and Seedling Length Inhibition.

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