Macroline alkaloids

In another study of the leaves of the same plant, several new monomeric alkaloids were obtained (in addition to bisindoles, vide infra) including the macroline alkaloid, 19,20-dehydro-... 

Ein anderes Beispiel ergab sich im Zusammenhang mit der Strukturauf-klarung des dimeren Alkaloides Villalstonin 19, 31). N(b)-Trideutero-methyl-macrolin-chlorid (17) wurde auBerhalb des Massenspektrometers... 

A partial synthesis101 of alstonerine (178) from macroline (179) (shown in Scheme 17) is of considerable interest, in view of the strategic position occupied by macroline as a possible precursor of both the monomeric Alstonia alkaloids (e.g. alstonerine) and the dimeric alkaloids (e.g. villalstonine and macralstonine). 

The absolute configuration of (-t-)-macroline, obtained by degradation of the dimeric alkaloid villalstonine, follows70" from its transformation into a mixture of the tetracyclic base (138) and its C-20 epimer. Base (138) was also obtained by degradation of ajmaline (139), as outlined in Scheme 21 the C-20 epimer of (138) was similarly obtained from isoajmaline, which is epimeric with ajmaline at both C-20 and C-21. 

Pandicine (312), an air-sensitive, amorphous alkaloid from the leaves of Pandacastrum saccharatum Pichon, has a novel structure composed of macroline and highly oxygenated tabersonine units.135 Its structure was elucidated mainly by comparison of its H and 13C n.m.r. spectra with those of the macroline unit in villalstonine and the oxygenated tabersonine unit in cryophylline. There is at present no definitive proof for the relative stereochemistry of the two components of the pandicine molecule that depicted in (312) is simply based on the stereochemistry deduced for related monomers, namely talcarpine and hazuntinine. Presumably the ease of oxidation of pandicine is due to the facile formation of the quinonoid species (313). 

The amino acid derived carboxy group can be utilized as a functionality for further synthetic manipulations, e.g. for cyclization reactions to 1,3-bridged P-carbolines, using the Dieckmann reaction, a promising stereocontrolled approach to macroline-related alkaloids (Scheme 14). > ... 

Liu, X., Cook, J. M. General Approach for the Synthesis of Sarpagine/Macroline Indole Alkaloids. Enantiospecific Total Synthesis of the Indole Alkaloid Trinervine. Org. Lett. 2001, 3,4023-4026. 

Of a total of 31 alkaloids isolated from the leaves and stem-bark of Alstonia angustifolia, 11 were new and of these, eight were dimeric alkaloids, all of which possessed the macroline unit (83]. The predominant alkaloid present was the known dimeric alkaloid villalstonine (289). 

The stem-bark extract of the Malayan Alstonia macrophylla provided in addition to seven known alkaloids, three new indole alkaloids, lO-methoxyaflinisine (334), 10-methoxy-cathafoline (335) and alstonerinal (336) [226]. The latter is a type A macroline and coeluted with the known type B macroline, alstonerine (337) during chromatography, and proved resistant to further resolution by chromatography or fractional crystallization. Eventually a pure sample was obtained by reduction of a mixture of 336 and 337 to yield the isomeric alcohols 338 and 339, followed by oxidation of338 to yield alstonerinal (336). 

Certain Alstonia species of the family Apocynaceae contain bisindole alkaloids of interesting construction. These are (+)-villalstonine from Alstonia macro-phylla Wall., A. muelleriana, A. somersetensis F.M. Bailey and A. villosa Blume, (+ )-macralstonine from A. macrophylla Wall., and macralstonidine from A. macrophylla Wall, and A. somersetensis F.M. Bailey. A common unit of all three dimers is the monomeric indolic base macroline. 

As well as macralstonine71" and others, a new alkaloid,716 alstonisidine, has been isolated from Alstonia muelleriana. The structure (80) suggested for this dimer rests on spectral measurements, principally the presence of several ions in its mass spectrum which have the same mass numbers as characteristic fragment ions of authentic macroline and ajmaline alkaloids, the formation of a mono-0-acetate, of a triol with lithium aluminium hydride (fission of N—C—O), and the detection of formaldehyde after acid treatment. Formaldehyde was also detected after a model acid treatment of quebrachidine (81) and it is suggested that this rather surprising result can be explained, for both the dimer, believed to contain a quebrachidine unit, and for quebrachidine itself as shown [arrows in (81) and (82)]. 

Alstonisidine (alkaloid A) [C42H48N4O4 mp 325° [a] — 234° (EtOH)] was first isolated by Elderfield and Gilman from the aerial bark of Alstonia muelleriana 48) but its structure (56) has only recently been elucidated 39). The indoline portion of this structure resembles macroline (57) and may well be derived from it or from a common precursor the second unit is related to quebrachidine (58) and the linkage between the two components is of a novel kind. 

Villalstonine (109) has been partially synthesized (Scheme 32) from its two halves , pleiocarpamine (110) and macroline, in an analogous synthesis, a process which in this case reverses a degradation of the alkaloid. It is interesting to note that the partial synthesis may well procieed via 11), in which electrophilic attack has occurred at the -position of the pleiocarpamine indole nucleus. As in the example discussed earlier (see p. 211) this / -substitution is secured by a subsequent intramolecular nucleophilic addition to the a-carbon, C-2. 

Advances in the chemistry of macroline, sarpagine, and ajmaline-related indole alkaloids 06T8655. 

Tan SJ, Lim KH, Subramanian G, Kam TS. Macroline-sarpagine and macroline-pleiocarpamine bisindole alkaloids from Alstonia angustifoUa. Phytochemistry 2013 85 194-202. 

Synthesis of Sarpagine/Macroline-Related Indole Alkaloids... 

Indole alkaloids of the sarpagme/ajmaline/macroline type comprise one of the most important groups of structurally related natural products. Many compounds of this class of alkaloids have been isolated mainly from the genera Alstonia and Rauwolfia of the family Apocynaceae. ° Much of the early isolation and stmctural work was performed on the Alstonia alkaloids in the laboratories of Elderfield and Schmid and was followed by the biomimetic interconversions of LeQuesne et al. " ... 

---