Daffodils lycorine

Lycorine (69) was recognized as a potent emetic and a moderately toxic base from the time of its initial isolation from Narcissus pseudonarcissus E. (in about 1877) (48). Since that time its isolation from many other AmaryUidaceae, for example, Lpcom radiate Herb., has served to estabUsh it as the most cosmopohtan alkaloid of the family. TypicaUy, as much as 1% of the dry weight of daffodil bulbs may consist of lycorine (69), which has been reported to... 

In Clivia miniata, O-methylnorbelladine (343) carrying 3H labels ortho to the phenolic hydroxy group of the tyramine-derived part and reference labels elsewhere is incorporated into lycorine and clivonine with the loss of both the 3H atoms. To explain this result, which contrasts with the previous one in daffodils (95), feeding experiments with [2/3-3H 5-14C]norpluviine (10) and [2a-3H 5-14C]caranine (2) were devised. The first precursor was isolated from daffodil in separate... 

In daffodil plants, galanthamine (147) is biosynthesized from the aminophenols 397, 398, and 399 but not from 343 which is, however, in the same plants a good precursor of haemanthamine (318) and lycorine (1) (Vol. XI, p. 397). These experimental results were interpreted as proving the existence of a definite order of methylation of norbelladine (399) during the biosynthesis of 147. Thus, methylation takes place in the first instance at nitrogen to give 398, later converted into 397. 

The first, oriAo-labeled precursor O-methylnorbelladine, was incorporated in Twink and Deanna Durbin daffodils into lycorine (ca. 50% 3H retention), haemanthamine (ca. 100% 3H retention), and narciclasine (ca. 75% 3H retention). The 75% 3H retention observed... 

The lycorine alkaloids come from plants such as daffodils. Among the simplest are the lyco-ranes 71-73 differing only in stereochemistry. They contain a saturated six-membered carbocyclic ring and that might make you think immediately of the Diels-Alder reaction. 

Conflict exists in deciding on the stereochemical course of the hydroxylation at C-2 of, e.g., norpluviine (100), which leads to lycorine (104). One set of results indicates that hydroxylation occurs with normal retention of configuration82 whereas the other set, obtained in a different plant, indicates that the reaction occurs with unusual inversion of configuration.83 The conversion of [2/8-3H, 9-OMe - 14C]pluviine [as (101)] into galanthine (103), in King Alfred daffodils, with retention of 79% of the tritium label confirms that the hydroxylation of C-2 may occur with inversion of configuration.80... 

The phenanthridine alkaloid lycorine (narcissine, galanthidine) (MD—Phe G5N C6) has a widespread occurrence and inhibits protein synthesis. Like lycorine, the structurally similar alkaloids dihydrolycorinine, haemanthamine, narciclasine, pretazettine and pseudolycorine also inhibit protein synthesis at the level of peptide bond formation. Galanthamine (lycorimine) (Phe C6N C40 C6 ), from daffodil bulbs but also of widespread occurrence, is both a nACh-R allosteric modulator and an inhibitor of AChE. Galanthamine is clinically employed in the treatment of Alzheimer s disease (dementia linked to deficiency in acetylcholine-mediated signalling in the central nervous system). 

Although norbelladine was shown not to be a precursor of galanthamine (101) in King Alfred daffodils, an incorporation of this compound with labels as shown (103), comparable to that for lycorine (104), has been obtained for galanthamine in Leucojum aestivum As expected, the lycorine showed loss of half its tritium. On the other hand, no loss of tritium was apparent in the galanthamine. The latter result suggested that in the biosynthesis of galanthamine conversion of (105) to narwedine (100) was either not reversible or, if so, enzy-mically controlled. 

The epoxide (86) has been tentatively invoked to explain the unusual hydroxy-lation with inversion of configuration at C-2 of norpluviine (84) which leads to lycorine (85) in daffodils. (In Clivia miniata on the other hand hydroxylation occurs with normal retention of configuration ). It was considered that an analogous epoxide (87) could give narcissidine (88) in the manner shown by loss... 

The conversion of the o-methoxyphenol to the methylenedioxy group may occur late in the biosynthetic pathway. Tritiated norpluviine is converted to tritiated lycorine by the Deanna Durbin daffodil. This transformation not only demonstrates the conversion of an o-methoxyphenol to the methylenedioxy group but also indicates that the C-2 hydroxyl group of lycorine is derived by allylic oxidation of either norpluviine or caranine. This late-stage hydroxylation was suspected when it was found that hydroxynorbelladine (CCXXVIII R,Ri,R2,Rs = H OH instead of H ortho to RgO) was incorporated into lycorine with extremely low efficiency. 

Synthesis of alkaloids of the first structural type [such as lycorine (8), norpluviine (9), lycorenine (10), and homolycorine (11)] in various daffodil varieties may occur as indicated (Fig. 33.4). Radioactively labeled norbellidine (5) is incorporated into norpluviine (9). 

In daffodil plants, galanthamine is biosynthesized from compounds 19-21, but not from norbelladine (5) [which is a good precursor of haemanthamine (14) and lycorine (8) in the same plants] (Fig. 33.6). These experiments suggest a definite order of methylation of norbelladine (5) during the biosynthesis of galathamine. In feeding experiments with the plant Leucojum aestivum, [2,4- H2 C-0-methyl]0-methylnorbelladine (13) is a precursor of galanthamine (18) that retains the same ratio as in the precursor. There... 

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