Lythraceae

Lasubines I and II are alkaloids containing a 4-arylquinolizidine substructure that have been isolated from plants of the Lythraceae family and have attracted the attention of synthetic chemists for some time. While numerous racemic syntheses of these and related compounds have been reported, only a few enantioselective syntheses are known. Some examples of these syntheses are given below, and the strategies involved in these examples are summarized in Scheme 92. Three of these syntheses involve the creation of the quinolizidine system by formation of one bond at the a- or 7-positions, while the fourth approach is based on a ring transformation associated with a photochemical Beckmann rearrangement. 

Little of the chemistry of the Lythraceae was known prior to the 1960s beyond reports of the qualitative presence of alkaloids in a few genera. With the recognition of the novel alkaloid structures in Decodnn and Heimia, an examination of material from other genera gleaned from herbarium specimens was undertaken. The published results are included in those reported here. 

A tropical Old World family, its habitats are the mangrove and rain forest areas. It is related to the Lythraceae. Alkaloids have been recorded for Sonneraliu but they have not yet been characterized. 

Lythraceae Alkaloids.—Results showing that lysine (15) is a precursor for decodine (22) and decinine (23) in Decodon verticillatus, which were published in preliminary form (cf. Vol. 1, p. 6), are now available in a full paper.8 Label from either C-2 or C-6 of the amino-acid was found to be spread equally over C-5 and C-9 of the alkaloids, indicating that ring A derived from this amino-acid and that incorporation was via a symmetrical intermediate. Cadaverine (16),... 

A key stage in the biosynthesis of piperidine alkaloids is reached with the formation of A -piperideine. For the elaboration of diverse alkaloids, this intermediate undergoes condensation with a variety of nucleophiles, commonly a /3-keto-acid. (A similar situation is found for pyrrolidine alkaloid biosynthesis see, e.g., Scheme l).1,2 Existing evidence on Lythraceae alkaloid biosynthesis, taken up again below, indicated that condensation occurred in this case between A piperideine (17) and acetoacetic acid to give pelletierine (26), further elaboration yielding alkaloids like (22). In the event, however, labelled pelletierine was found not to be a precursor for (22) or (23).8 Negative evidence is always difficult to interpret, but is here made persuasive by the fact that other precursors that were fed concurrently were incorporated. Conclusive support for these results depended on others outlined below. 

The nature of the nucleophile which condenses with A piperideine (17) needs to be reconsidered. Very plausibly, this could be (18), which is formed as shown in Scheme 3 from phenylalanine (20) via cinnamic acid (19) and malonyl-CoA. A further unit of this type is found in alkaloids such as lythrumine (24). An outline biosynthetic route to Lythraceae alkaloids is given in Scheme 3.9... 

The plants of Lythraceae family are moderately well distributed in different regions of the world, from the tropics to the temperate zones, and are especially abundant in Latin America. The family consists of 22 genera composed of about 500 species, including several economically important... 

The first isolation of the Lythraceae alkaloids from Decodon verticillatus (L) Ell was reported by Ferris in 1962 (2). Those were lactonic biphenyl alkaloids (type A) decinine, decodine, verticillatine, decamine, vertine, lactonic ether alcaloids, decaline, and vertaline. 

In 1967, Fujita et al. (5,6) isolated three piperidine metacyclophane alkaloids (type B) from Lythrum anceps Makino. The third structural variant of the Lythraceae alkaloids, quinolizidine metacyclophane (type C), was... 

Brief references to the Lythraceae alkaloids have been made in Volumes X, XII, and XIV of this treatise. A short review on the alkaloids from Lythrum anceps was published in Japanese (14). A review on the Lythraceae alkaloids has appeared recently, covering mainly structure elucidation (15). 

The numbering system used for lactonic Lythraceae alkaloids is that introduced by Spenser (10) and originally employed by Schopf et at. (11). The system closely corresponds to the that introduced by Fujita et al. (12, 13) for metacyclophane alkaloids (B and C). The new system is attractive since the carbon atoms that correspond in biogenetic origin to the three types (A, B, C) maintain corresponding numbers. 

The methoxyl groups of nesodine absorb in the NMR at 3 3.98 and 3.69 ppm. The former signal may be assigned to 22-OMe and the latter to 21-OMe. The data do not eliminate an alternative structure (16) (structure 1 with R1 = H, R2 = OH, R3 = Me) for nesodine. Ferris et al. preferred 5 to 16 on the basis of the fact that no naturally occurring Lythraceae alkaloid has a 21-OMe. It would, however, be necessary to confirm this structure by internal ether formation. 

The Lythraceae alkaloids have four centers of chirality—three chiral carbon atoms at the quinolizidine ring C-l, C-3, and C-5, and the dissy-metric biphenyl or biphenyl ether link. The chirality of the biphenyl system in all alkaloids of the group is the same. The chirality of the biphenyl ether link is also the same for all alkaloids in this class (22, 23, 32). 

Lagerine was isolated by Ferris et al. from Lagerstroemia indica (17), and methyllagerine was isolated by Hanaoka et al. (42) from L. indica grown in Japan. The structure of lagerine is unique since it was not possible to convert this base to any known Lythraceae alkaloid. The basic skeletons of O-methyllagerine and vertaline are the same since the mass spectra of the two alkaloids are almost identical. The alkaloids differ in the substitution pattern on the biphenyl ether chromophore, a fact which is reflected in the UV spectra. 

Five new alkaloids have been isolated from the Lythraceae plant Lythrum Lanceolatum by Wright et al. (9). The structure and absolute configuration of two of these bases, lythrumine (123) and monoacetyllythrumine (124), were established on the basis of the X-ray analysis on lythrumine hydrobromide. On acetylation both the alkaloids yielded the same diacetate (125). 

Lythraceae plant family and suggests that the metacyclophane and lactonic alkaloids have a common biosynthesis. 

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