Dimeric triterpenes

Itokawa et al. [71] have recently isolated and characterized four new dimeric triterpenes from M. illicifolia (Paraguay), three of which have two units of pristimerin while the fourth (cangorosin B) has one pristimerin and one tingenone unit (Fig. 11). 

ANTIMRICROB1AL AND CYTOSTATIC ACTIVITY OF TRITERPENES AND DIMER TRITERPENICS... 

Compound (96) showed to be a dimeric triterpene based on its spectral data and showed a molecular formula of C61H84O9, based again on its... 

Compound (96) was considered a dimeric triterpene with the formula C61H84O9, based again on its HRFAB-MS and 13C-NMR data. 

A good example of the simplicity and power of the chemistry to rapidly construct complex systems is provided by the Kolbe dimerization of (55) as the key step of a total synthesis of the triterpene (+)-Q -onocerin (57 Scheme 14) [33], Thus, oxidation of (+)-hydroxy keto acid (55) in methanol containing a trace of sodium methoxide and at a temperature of 50 C, followed by acylation and chromatography, provided (+)-diacetoxydione (56) in a 40% yield. 

An optically active dicarboxylic acid lignan (caffeic acid dimer), named epiphyllic acid was isolated from liverwort as well as its derivatives, which do not belong to any typical lignan-producing subgroups. They also occur in some vascular plants, even as a triterpene ester of epiphyllic acid in Rhoipte-lea chiliantha [37]. The conversion of caffeic acid to epiphyllic acid was demonstrated by Tazaki et al. [38]. However, little is known about the biosynthesis of this type of lignan in vascular plants yet. 

Itokawa H, Shirota O, Morita H, Takeya K, Tomioka N, litaka 106. Y. Triterpene dimers from Maytenus ilicifolia. Tetrahedron Lett. 1990 31 6881-6882. 

Shirota 0,Sekita S, Satake M, Morita H, Takeya K, Itokawa H. Nine regioisomeric and stereoisomeric triterpene dimers from Maytenus chuchuhuasca. Chem. Pharm. Bull. 2004 52 739-746. Shirota O, Sekita S, Satake M, Morita H, Takeya K, Itokawa H. Two new sesquiterpene pyridine alkaloids from Maytenus chuchuhuasca. Heterocycle 2004 63 1891-1896. 

Triterpene dimers have recently been reported and are generally characterized by die presence of modified triterpene quinone monomer units. To date, ten dimers based on tingenone and/or pristimerin units have been described, most of them from the Maytenus genus [67]. 

Triterpene dimers with modified quinone or phenol skeletons also exhibit antimicrobial activity [68] and have also been synthesized [68,70]. 

Table XXVI shows the MIC (minimum inhibitory concentration) of the different products tested on Gram positive and Gram negative bacteria the former proving to be more susceptible to the activity of the compounds except for product 125 which had no effect whatoever on either. Bacillus species proved more sensitive than Staphylococcus aureus and this seems to be a general trait of quinone triterpenes such as netzahualcoyone, tingenol and pristimerin which are all more active on B. subtil is than S. aureus. The most active compound was 122, its MIC on B. subtilis (1-2 pg/ml) being particulary interesting. The dimers were less active than the monomers.

Dimers are a class of compounds isolated from only seven species of Celastraceae family [8,88]. These triterpene dimers were found to be composed of one quinoid type and one aromatic type of triterpene derived from pristimerin, tingenone and / or their congeners joined together by two ether linkages formed between the two A rings or between the A and B rings. From the methylene chloride soluble portion of a methanolic extract of Maytenus chuchuhuasca, four dimeric compounds were isolated by Shirota et al. [88]. 

Compound (94) showed a molecular formula of CeoHgoOs, based on HRFAB-MS analysis and its l3C-NMR spectrum. According to the data obtained from its H and 13C-NMR spectra suggested that (94) was a triterpene dimer composed of two pristimerin-type triterpenes with one subunit in the quinoid form and the other in the aromatic form. Confirmation of the structure was made by analysis of the 2D NMR spectroscopic data. The absolute configuration was determined from its CD spectrum. According to the above data, the authors concluded that (94) was a regioisomer of scutionin aA [89], and it was called scutionin aB, Fig. (50). 

Triterpene dimers and trimers discussed in the present review probed to be inactive as cytotoxic [91,8]. According to Gonzalez et al., this fact is due that the size of this type of compound plays an important role in their activity and that they could be stored in the plant as polymers, which could release biologicaly active units, like the quinone methides. 

The isolation of 52, from M. ilicifolia, whose 24-positional carbon is oxidized to formyl moiety, is worthwhile from the viewpoint of biogenesis, because it suggests a biogenetic route caused by the oxidative elimination of the 24-Me from friedelin to pristimerin-type triterpenes, and furthermore to triterpene dimers. Also cytotoxic activities of isolated compounds against V-79, KB and P388 cells were examined. The results are summarized in Table V. Pristimerin (57) exhibited the strongest activity. 

H. Itokawa, O. Shirota, H. Morita, K. Takeya, N. Tomioka and A. Itai, "New Triterpene Dimers from Maytenus ilicifolia . Tetrahedron Lett., 1990,31, 6881-6882. 

---