Celastroloids

Gunatilaka, A. A. L. Triterpenoid quinonemethide and related compound (celastroloids). In Progress in the Chemistry of Organic Natural Products Hertz, W. Kirby, G. W. Moore, R. E. Steglich, W. Tamm, C., Eds. Springer-Verlag New York, 1996 Vol. 67, 1-123. 

The first structure of a celastroloid described with this type of modification was the 7-oxoquinonemethide dispermoquinone (72), isolated from M. dispermus [80], Fig. (37). 

Bearing a 7-oxoquinonemethide structure, but with a skeleton related to tingenone insted of pristimerin, as exhibited by dispermoquinone, a new celastroloid (73) of this uncommon type was isolated from the roots of M. amazonica by Chavez et al. [81]. The structure was elucidated by spectroscopic evidences, exhibiting a molecular formula C28H32O5, and characteristic features of 7-oxo-quinonemethides in the H NMR spectrum as the signals of H-l and H-6 as non-interchangeable with D2O... 

A number of celastroloids with extended conjugation has been described [35]. But compounds lacking an insaturation on ring B had not been reported. A compound of this type (74) was also isolated from the roots of M. amazonica by Ch vez et al. [81] as an amorphous white solid, unlike the yellow to red colors exhibited by the rest of the quinonemethide triterpenoids. 

The first natural celastroloid-related structure described bearing a phenolic system in ring A was zeylasterone (75), isolated from Kokoona zeylanica [82]. That compound was characterized as a 6-oxo-diphenol derivative of pristimerin (53). 

The chemical study M. amazonica roots [81] conducted to the identification of seven new phenolic triterpenes, besides the two new celastroloids discussed above. The structure of compound (83), isolated as yellow crystals, was determined by spectroscopy. HREIMS indicated a molecular formula C28H34O6, and it showed IR absorption bands for carbonyl (1685, 1720 cm 1) and hydroxyl (3550 cm 1). 13C-NMR experiments indicated a phenolic triterpene related to 6-oxo-tingenol [85]. 

S. krausii is used in Mozambican traditional medicine against bilharziasis and dysentery. However, Celastraceae plants were also reported to possess antimalarial activity [35]. Figueiredo et al. isolated three nor-triterpene quinone methides [77], compounds (60), (61) and (62). The in vitro activity (expressed as IC50 values) of the isolated quinone methides in comparison to the reference compound (chloroquine) is shown in Table 6. The isolated compounds, together with the known celastroloids celastrol (52), pristimerin (53) and isoiguesterol (101), Fig. 

In the course of these research programmes, many characteristic bioactive compounds have been reported. Polyester sesquiterpenes and pyridine-sesquiterpene alkaloids with insect antifeedant or insecticidal properties have been isolated from some species and recently sesquiterpene pyridine alkaloids with immunosuppressive or antitumoral activities have also been described. Diterpene triepoxides with potent antileukemic and immunosupressive activities and triterpenoid quinonemethides, named as celastroloids , with antibiotic and cytostatic activities, have been isolated from species of the Celastraceae family. 

The triterpenoid quinonemethides constitute a group of unsaturated and oxygenated D A-friedo- or-oleananes, and in nature these pigments are found restricted to the Celastraceae. They are considered to be indicators of the family and Bruning and Wagner [6] coined the general name celastroloids for this class of compounds. 

The pioneering work of Bhatnagar and Divekar encouraged subsequent workers to search for bioactive compounds in the Celastraceae species and since the discovery of celastrol (172) and pristimerin (173), a variety of celastroloids have been encountered in plants of this family. 

Celastroloids may be classified in several different ways depending on their structural features and a classification based on the nature of the main chromophore could be considered. According to its conjugation there are four different structiu es of norquinonemethide triterpenoids those with... 

The most common and basic class of celastroloids are those with a quinonemethide chromophore extended over the A and B rings of the triterpenoid skeleton. In all of them, the C-29 methyl group has undergone partial oxidation to -CH2OH (eg. excelsine, 178) [242] or complete oxidation to -CO2H (e.g. celastrol, 172) sometimes followed by methylation to produce -C02Me (e.g. pristimerin, 173). Several examples... 

The second major group of celastroloids are constituted by those compounds with a chromophore extended to the ring D of the triterpenoid... 

Phenolic and 6-oxophenolic triterpenoids have also been reported. Zeylasterone (182) was the first celastroloid in this class to be described... 

A review which contains comprehensive discussions on distribution, structure elucidation, chemistry, biological activity and biosynthetic aspects of celastroloids, covering the literature up to 1994, have been published by Gunatilaka [251]. For this reason, the present review only emphasises the results on the biological active celastroloids reported during the period 1994 to 1997. 

A. AX. Gunatilaka Triterpenoid Quinonemethides and Eelated Compounds (Celastroloids)... 

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