Secoiridoids structures

Gentiopicroside is also contained in the herbal medicine Gentiana (Ryutan), which is the extract of the root of Gentiana lutea and has gastroprotective effects.117 It has a secoiridoid structure, which is a common constituent in members of the family Gentianaceae. 

Secoiridoids are complex phenols produced from the secondary metabolism of terpenes as precursors of several indole alkaloids (Soler-Rivas and others 2000). They are characterized by the presence of elenolic acid, in its glucosidic or aglyconic form, in their molecular structure. Oleuropein, the best-known secoiridoid, is a heterosidic ester of elenolic acid and 3,4- dihydroxyphenylethanol containing a molecule of glucose, the hydrolysis of which yields elenolic acid and hydroxytyrosol (Soler-Rivas and others 2000). 

A revised structure for the secoiridoid xylomollin (176) has been proposed on the basis of lH coupling constant data and the revised trans-fused arrangement was confirmed by crystallographic analysis (78JA7079). Both rings are in a chair conformation and the bridgehead hydrogen atoms are disposed trans to each other. 

Figure 8. Chemical structures of secoiridoid derivatives and phenolic alcohols in virgin oiive oiis.

The stereochemistry of alcoholysis of the structurally related swertiamarine, lamiide, and ipolamiide is shown, (124) to (125). In the secoiridoid series,... 

Iridoids are derivatives of monoterpenes and occur usually, but not invariably, as glycosides.100,101 Structurally, they are cyclopentano [r] pyran monoterpenoids and they provide a biogenetical and chemotaxonomical link between terpenes and alkaloids. The cleavage of the cyclopentane ring of iridoids produces secoiridoids.10... 

Several new secoiridoid glucosides711-714 and a bis-diglucoside composed of linked iridoid and seco-iridoid units715 have been isolated and characterized. Of numerous other reports on these compounds, a selection is noteworthy in recording new compounds,716-734 ascertaining or correcting structures of known com-... 

Before 1960, one of main components of olive, the oleuropein, was studied in Roma. Panizzi s research group established the structure of this monoterpene glucoside, die leader of the group, that only several years later was identified as secoiridoids. Panizzi s group has isolated two other compounds the oleuropeic acid that is a monocyclic monoterpene, and its saccharose derivative. 

In the olive, there are two main compounds, besides that reported in the literature. The first one is oleuropein, the first secoiridoid isolated in 1960 by Panizzi in Roma, as mentioned above. The second one is the comoside that is a hemiquinone glucoside, structurally and biogenetically related to hydroxy-tyrosol that is the principal free phenol in the olive. It should be remembered that, depending on the olive cultivar, the oleuropein can be prevalent against the comoside, or it could be the contrary, until reaching the equality. 

Oleuropein 1 is the first secoiridoid whose structure was recognised in 1958-65[1-3], but only several years later it was classified as secoiridoid, when this class of monoterpenoids was constituted. 

Iridoids are monoterpene compounds characterized by a cyclopenta [c] pyranoid skeleton, also known as the iridane skeleton (cis-2-oxabicyclo-[4, 3, 0]-nonane). These are also found to occur in a variety of animal species. In a broad sense, it is acceptable to include in this group the secoiridoids, which arise from the latter by cleavage of the 7, 8 bond of the cyclopentane ring. This group (of about 500 known structures) chiefly comprises iridoid glycosides (>300), secoiridoid glycosides (>100), and non glycosidic compounds (>100). 

ABSTRACTS The iridoid and secoiridoid derivatives of Oleaceae have been grouped regarding structural similarities. The biosynthetic routes leading to these compounds and their most relevant biological activities, described up to now, have also been reviewed. 

Among the most frequent compounds isolated from species of this family are iridoids and secoiridoids. The term iridoid is used to design a wide group of monoterpenes, in most cases, as glycoside derivatives, whose structure may be considered as deriving from iridane (cis-2-oxabicycle-[4.3.0]-nonane (1). The secoiridoid-type of compounds derive from iridoids by elimination of the link 7-8, to give rise to tine basic structure (2). 

In this work, we want to keep the structures of the iridoids and secoiridoids which are present in Oleaceae, their biosynthesis and the biological activities, so far described, up to date. 

The tables 1 - 7 contain the structures of the iridoids and secoiridoids from Oleaceae. The reference and the natural origin correspond to the first cite in which the compound has been named. In any case, secoiridoids such as oleuropein (81), ligustroside (82) and many others can be obtained from several species. 

Iridoids and secoiridoids, as it happens in other groups of natural products, may show an ample variety of structures. It is well known that the biochemistry, the physiology, and the morphology of a plant is subdued to evolutional pressure. During millions of years of evolution, countless number of products have been synthesized by different species, and we can wonder what may be the sense for the plant to contain such as enormous amounts of variants in a sort of metabolic orgy that seems to be senseless. We must not forget that the variability is the bases for natural selection. 

The iridoids are a group of monoterpenoids with the methylcyclopentane skeleton, based on the structure of iridane. In the widest sense, iridoids also can include secoiridoids, where the cyclopentane ring is opened between the positions C-7 and C-8. Fig. (1). 

Many reviews have dealt with the distribution, structure, properties and biosynthesis of iridoids and secoiridoids [131-137] without distinguish between the biosynthetic pathway route. In our case, some of the most studied activities, as anti-inflammatory, antitumoral-chemopreventive, and protective by iridoids biosynthesized by route IIa, have been discussed. 

In order to explain and confirm the biological activities claimed by the traditional medicine, and to search for new biologically active compounds we studied the antimicrobial, antioxidative, immunomodulatory, antiinflammatory, skin-regenerating and antiviral properties of Fraxinus ornus bark extract and its components. In a parallel detailed phytochemical investigation of the extract we isolated and determined the structures of many hydroxycoumarins, secoiridoid glucosides, caffeoyl esters of phenylethanoid glycosides, lignans and other phenolic compounds. 

Our paper on isolation and structure elucidation of omoside was already in press, when the publications of Tanahashi et al. [18] and Shen et al. [19] appeared in Phytochemistry. Tanahashi and co-authors were the first to report the isolation and structure determination of a novel secoiridoid glucoside from F. insularis, named insularoside, and to assign structure 15 to this compound. Later, Shen et al. described the occurrence of insularoside in Fraxinus uhdei under the name uhdoside [19,20]. 

Therefore, almost simultaneously and independently the secoiridoid glucoside 15 has been isolated from three different Frctxinus species under three different names. Our approach in its structure elucidation provided some additional data and more chemical evidence about this unusual secoiridoid. 

This gave us a reason to study and compare [35] the antimicrobial properties of a series of Fraxinus ornus bark constituents - the hydroxycoumarins 1-4, 6-7, 11-12, and acetates 2a and 4a the secoiridoids 14, 14a, 15, 15a, and the tyrosol derivatives 29 and 30 applying the method described by Bankova et al. [36]. In this case the antibacterial properties of the studied compounds were also dependable on their structure and substitution (Table 8). 

Following the LC/MS screening results, a targeted isolation of 10-13 was undertaken and full structure determination of 10 showed it to consist of two secoiridoid units linked together with a monoterpene unit through two ester groups (Fig. 7) [25], Compounds 11 and 12 have proved to be of the same type but with two supplementary monoterpene units [26]. All these compounds are a new natural products. 

---