Sesquiterpene lactones structural types

In 1959-61, a Czech group [8,9] reported the isolation of a new sesquiterpene lactone from Chrysanthemum (Tanacetum) parthenium as part of a study of the sesquiterpene lactones of the Compositae family. They named it parthenolide. The initial structure for parthenolide was later revised [10,11] and the accepted structure for parthenolide today is represented by structure (1). Parthenolide is a germacranolide-type sesquiterpene lactone. The crystal structure for parthenolide has also been reported [12]. Extractions of C. (T.) parthenium grown in Mexico, known locally as santamaria, did not yield parthenolide [13], but a closely related compound was isolated and named santamarine (3). This suggests that regional variations in the chemical constituents may occur. 

A (4) and B (5) structures originally presented [15] were wrong and that these compounds do not occur in feverfew. Canin (19) is an example of a guainolide-type sesquiterpene lactone. 

Figure 1. Structural types of sesquiterpene lactones in Helianthus ...

Finally it should not remain unmentioned, that several STLs of other structural types have been found which contain a cyclic peroxide structure. The STL database (see Structural diversity of sesquiterpene lactones ) contains 88 entries with peroxide moieties of which 24 contain this structure as part of a ring system. Of these, 21 are not derived from seco-cadinane but belong to the guaianolide and xanthanolide series. It remains to be shown whether these compounds possess anti-protozoal activity in a similar way as the artemisininoids. 

Our own work on structure-activity relationships of convulsant sesquiterpene lactones was initiated after isolation of a variety of seco-prczizaanc type compounds from Illicium floridanum and I. parviflorum, both endemic to the southern United States [157, 179-181]. A study on the in-vivo toxicity of several of these compounds [182] showed that anisatin, major constituent in leaves and fruits of I. floridanum (as in those of other previously studied toxic Illicium (=star anise) species, review see [3]), was apparently the only derivative in the tested series which was toxic to mammals, although further compounds, such as pseudoanisatin (PSA, structure 4 in Fig. (27)) were accumulated in the plant in similarly high amounts [179, 180]. In the light of reports that indicated an identical mechanism of action and -possibly- the existence of a common binding site for anisatin and picrotoxinin [156-161] the question arose which structural features in these compounds were similar enough to warrant an identical mode of molecular recognition at the channel protein. 

Spanish researchers [24] have undertaken the synthesis of 11 -angeloxy-a-santonin (104) in an attempt to clarify the stereostructures of decipienin A and other sesquiterpene lactones isolated from Umbelliferae species, i.e. structures of type 91(a) (5j8//, 6aH, laH, 10a, llj8-methyleudesman-6,12-olide) versus structures of type 91(b) 5aH, 6fiH, laH, 10j8, 1 la-methyleudesman-6,12-olide). Structures of type 91(b) were, as a result of this synthesis, shown not to be present in such compounds. 

Sesquiterpenes are aliphatic or cyclic, isoprenoid Cl5 -compounds encompassing an almost bewildering array of structural types (cf. Figs. 106-108). They may be saturated or contain isolated double bonds. Often hydroxy, oxo, aldehyde, carboxylic acid, and lactone groups are present. Most compounds are volatile and lipophilic. Nitrogen-containing sesquiterpenes (sesquiterpenoid alkaloids) occur in some families of higher plants. 

The opening of the spiro (3-lactone of the anisatin-type sesquiterpene leads to the minwanensin-type. The structure of minwanensin (34) from the pericarps of I. minwanense was elucidated [9] and later revised by X-ray crystallographic analysis of its p-bromobenzoyl derivative [23], as shown in Fig. (6). This type of compounds, such as 3-acetoxy-14- -butyryloxy-10-deoxyfloridanolide (35), 14-acetoxy-3-oxofloridanolide (36), 13-acetoxy-14-(n-... 

A number of new majucin-type sesquiterpenes having a y-lactone ring as shown in Fig. (7) were found in the pericarps of I. majus, belonging to one of the Chinese Illicium plants. Majucin (43) was the first to assign structure by extensive spectroscopic analysis and... 

The maytolins are an interesting instance of new sesquiterpenes from the Celastraceae characterized by the presence of a tetrahydro-oxepine nucleus. It would seem that these new types of skeleton are only biosynthesized by species of the Mortonia genus, which consists of just four species, endemic to Mexico and the southern United States. The structures proposed for mortonins A and B, Fig. (4), are the first recorded examples of a natural product in which ring B of the eudesmane skeleton undergoes oxidative cleavage to the the y-lactone [126]. 

Apart from the diversity presented by their core structures, sesquiterpenes are commonly decorated with lactone moieties and hydroxyls throughout the basic core. Thus, usually isolated biologically active natural sesquiterpenes are highly oxidized, referred in the literature as sesquiterpe-noids. The a,p-unsaturated lactone functionality is a common feature of many cytotoxic sesquiterpenoids accounting as a powerful alkylating side through a Michael-type addition to suitable biomolecules as the cysteine residues on proteins and enzymes. Thus, several biological active sesquiterpenoids have been isolated and used in traditional and modem... 

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