13C-NMR Spectral Data of Alkaloids Isolated from Psychotria Species (Rubiaceae)

The genus Psychotria (Rubiaceae) comprises more than 2000 species, mainly found in tropical and subtropical forests. Several studies have been conducted concerning their chemical compositions, showing that this genus is a potential source of alkaloids. At least 70 indole alkaloids have been identified from this genus so far. This review aimed to compile 13C-NMR data of alkaloids isolated from the genus Psychotria as well as describe the main spectral features of different skeletons.


Introduction
In phytochemistry and related areas, structural elucidation techniques play a key role because precise knowledge of the chemistry of plants requires unequivocal structural characterization of its metabolites to obtain information related to the taxonomy of plant groups. Moreover, correct identification of biologically active compounds is important, both to understand their possible mechanisms of action and propose chemical modifications aimed at enhancing their activity.
The characterization of natural products requires, apart from patience and dedication, knowledge about spectroscopic techniques (interpretation of these data) and the biosynthesis of different types of metabolites. Comparison with literature data is another important auxiliary tool that aids the structural characterization of a given compound. In this context, finding a material that provides as much information as possible about the spectral data of metabolites isolated from a genus (such as Psychotria) may enable saving time.
The genus Psychotria (Rubiaceae) comprises more than 2000 species, which occur mostly in tropical and subtropical regions [1], with many of these species being employed in folk medicine to treat several diseases [2,3]. The biological potential of the chemical constituents of the species of this genus has possibly motivated several studies regarding the chemical composition of such species. Most of these have focused on investigating alkaloid fractions obtained by acid-base extraction, probably owing to the biological importance of this type of metabolite. Such efforts have led to the isolation 5.4 (CH-10) ppm), showing that the downfield displacements of the CH-12 and CH-10 signals may be used to suggest that N-1 is attached to C-22. There are some examples of alkaloids isolated from this genus, whose biosynthesis involves hydrolysis of a glycoside moiety such as (E/Z)-vallesiachotamines, 23 and 24, isolated from P. bahiensis [17], and10-hydroxy-iso-deppeaninol (27) and N-oxide-10-hydroxyantirhine (29) isolated from P. prunifolia [20]. These types of skeletons may be suggested by analysis of the region of the 13 C spectrum that is typical of sugars, revealing the absence of the typical signal of the anomeric carbon around δ C 100.0, apart from additional signals of the oxy-carbons characteristic of this unit. Kerber et al. reported the isolation of a new MIA from P. brachyceras leaves [21], named brachycerine (33), which showed a new alkaloid skeleton. Its biosynthesis involved the coupling of tryptamine to a 1-epi-loganin derivative. Psychollatine (34), a new MIA from P. umbellate [22], presented a terpenoid derivative from geniposide. Both alkaloids as well as compounds 21, 22, and 35 revealed an important characteristic in their 13 C spectra: the absence of typical signals of a terminal vinyl group (~δ C 119 ppm). In contrast, bahienosides A (38) and B (37), isolated from P. bahiensis [17], showed duplicate terminal vinyl group signals relative to two secologanin moieties. Figure 2 shows typical carbon assignments, which may indicate some different structural possibilities in comparison with those values observed for strictosidine (1).

Compounds
Species References 13
Since some compounds with more than two units present a chimonanthine portion in their structures, the monitoring of C-3a and C-7 (main binding sites) and their neighborhood may be a good alternative, in order to determine the positions of the other monomeric units. Hodgkinsine (52) occurs frequently in the genus [41][42][43][44][45][46] and presents a third unit with a C-3"a-C-7' linkage. In this case, besides replacement of a methine aromatic carbon by a quaternary carbon (C-7'), observing the up field displacements of C-6' and C-4' (∆δ around 3.0 ppm) is possible probably because of the presence of a group that increases the electron densities of these positions (comparison with compound 40). Takayama et al. (2004), however, reported the isolation of psychopentamine (60) from P. rostrata 2 , which showed a new type of linkage between C-3"'a and C-5" [2].
The chemical study of P. calocarpa leaves [43] led to the isolation of a new alkaloid named psychotriasine (45), which presents a tryptamine unit linked to a pyrroloindole unit by an N-C3'a linkage. This type of junction was also observed for psychohenin (46) and compound 48 isolated from P. henryi [47,48] and may be indicated by the presence of a quaternary carbon (C-3'a) that resonates at δ C 79.4, 77.8, and 76.7 ppm, in the three compounds, respectively. In contrast, psychotrimine (53), isolated from P. rostrate [2] shows, besides the N-C-3'a bond, an N-C-7' linkage indicated by the signal of a quaternary aromatic carbon C-7' at δ C 121.5 ppm.
Alkaloids with more complex structures, containing from four to seven units, such as quadrigemines A-C (55-57), psychotridine (61), oleoidine (64), and caledonine (65), have also been isolated from this genus; however, the structural elucidation of these compounds becomes more difficult as the number of units increases. Probably owing to this, some studies did not provide detailed attributions of their carbon signals. In such cases, mass spectrometry plays an important role in establishing the number of units present in their structures as well as the pattern of the junctions.                    3 OD, II CDCl 3 e III benzene-d 6 , ns not specified; letters indicate signals that may be interchanged, nd = not detected; * indicates cases for which there was no complete detailed attribution of carbon signals.

Conclusions
In this work, we attempted to compile 13 C-NMR data of alkaloids isolated from the Psychotria genus and provide information that may be useful in order to distinguish different types of skeletons. For monoterpene indole alkaloids (MIAs), mainly found in tropical species, a good strategy for their structural elucidation is to compare their spectral data with those observed for strictosidine (1). The monitoring of differences in specific parts of the spectrum, such as the signals of C-22, CH-17, CH-12, CH 2 -5, and CH-1 , may suggest alternative structural possibilities. Note that all comparisons performed in this work are restricted where possible to compounds whose 13 C-NMR experiments were run in the same solvent.
The main pyrrolidinoindoline alkaloids found in this genus are chimonanthine derivatives, with units linked mostly by C3a-C3'a or C-3a-C7a bonds. Some examples have shown different patterns of linkages between N (from tryptamine terminal units) and C-3a. For compounds with more than three units, such as quadrigemines A-C and psychotridine and its isomer, obtaining detailed assignments of these carbons is not possible owing to structural complexity.The occurrence of benzoquinolizidine alkaloids in Psychotria species is less common, comprising some compounds isolated from Psychotria klugii.