Sideritis diterpenoids

Pang L, de las Heras B, Hoult JR. A novel diterpenoid labdane from Sideritis javalam-brensis inhibits eicosanoid generation from stimulated macrophages but enhances arachidonate release. Biochem Pharmacol 1996 51 863-868. 

A series e t-kaurane diterpenoids isolated from Sideritis species were tested against A2780 ovarian cancer cell lines, and 7-e/>/candicandiol (Fig. 6.6) showed the highest cytotoxic potential with ICj , = 9.0 pg/mL, and sidol followed it (ICj , = 15.6 pg/mL). 

Sideritis (Labiatae) have been a rich source of novel bi- and tetra-cyclic diterpenoids. Andalusol (10), which has been isolated from S. arborescens, was assigned the ent-labdane configuration. Its structure was deduced by a combination of spectroscopic measurements and an X-ray analysis of the degradation product (11). 

The beyerene diterpenoids isolated from Sideritis pusilla possess a C-l 4a-hydroxy-group. The 7,18-diacetate of pusillatriol (78) was prepared75 by rearrangement of the 15,16-epoxide of 7,18-diacetoxysideridiol, thus interrelating the two... 

The chemistry of atractyloside has been reviewed. A further relative (87) of cafestol has been isolated from green coffee beans. Sideritis (Labiatae) species have continued to attract attention as a source of diterpenoids. The comparative phytochemistry of Canary Island species has been reviewed. A number of 15-hydroxykaurenes (88)—(90) have been isolated from S. crispata, S. ilicifolia, and S. tragoriganum together with the atisine (91) and beyerene (92) derivatives, ent-18-Acetoxy-3/8,7a,15/S-trihydroxykaur-16-ene has also been obtained from S. scardica. 

Four new diterpenoid oxides have been obtained from Sideritis gomerae. They are gomeraldehyde (cnt-8,13-epoxylabdan-15-al) and gomeric acid (cnt-8,13-epoxylabdan-15-oic acid) and their 13-epimers. ent-Labda-13-en-8/8,15-diol was also isolated. 3/3-Hydroxymanoyl oxide and the 18-benzoyloxy-derivative have been obtained" from Palafoxia rosea. 

The examination of Sideritis species (Compositae) has continued to provide further diterpenoids. S. reverchonii contains the tricyclic lagascol and lagascatriol, the beyerenes tobarrol, benuol, jativatriol, 12-acetyljativatriol, and conchitriol, and the atisenes serradiol and sideritol. The X-ray analysis of isosideritol (ent-atis-13-en-7a,16o >17-triol), which was a minor diterpenoid from S. angustifolia, has been described. ... 

The genus comprises at least from 100 to 150 species [1], occurring in temperate and tropical regions of the Northern Hemisphere. The countries around the Mediterranean Sea, and especially Spain, Canary Islands and Middle East, are particularly rich. The taxonomic classification of the genus is rather complex. The chemical investigations on Sideritis were concerned with flavonoids, essential oils, and especially diterpenoids. Diterpenoids occur in almost all the species and show a remarkable variability of carbon skeleta... 

Another Spanish species, S. mugronensis, yielded boijatriol (117), a diterpenoid with manoyloxide structure and normal configuration [39]. This was the first case of a normal configuration in the diterpenoids of Sideritis. The structure was amended some years later [40], changing the position of the secondary hydroxy group from 6a to 70. 

As far as we know about synthetic studies, no total synthesis of the natural diterpenoids from Sideritis was reported, whereas many hemisyntheses and correlations are known. 

Some microbiological reactions were attempted either on natural kaurane diterpenoids isolated from Sideritis or on their hemisynthetic derivatives, by incubating them with Gibberella fujikuroi. The purpose was the transformation of the products into gibberelline derivatives. However, epicandicandiol (7) yielded no gibbane compounds, only oxidation of the 19-Me occurred, with the formation of the CH2OH and COOH derivatives (A) and (B) [112]. 

This biochemical profile distinguishes these diterpenoids from the antiinflammatory polyphenolics, such as flavonoids occurring in the genus Sideritis, and suggests that medicinal decoctions of these plants are likely to owe any anti-inflammatory activity to more than one bioactive ingredient. 

In a recent paper [106], the antibacterial activity was investigated on 27 known diterpenoids isolated from five species of Sideritis growing in Turkey. A certain activity, expressed as MIC (minimum inhibitory concentration), was observed for epicandicandiol (7) against E. coli and for sideroxol (54) against B. subtilis. 

Sideritis (Labiatae) species have continued to attract attention as a source of diterpenoids. n/-lljS,18-Dihydroxykaur-15-ene (49) was obtained from 5. chamaedryfolia and the known diterpenoids foliol (enr-3/8,7a,18-trihydroxy-kaur-16-ene) and its 3- and 18-monoacetates (sidol and linearol) were detected in S. arborescens ° and along with their A -isomers and 18-hydroxykaur-16-ene (candol B) in S. flavovirens. A similar group of hydroxykaurenes was found in S.funkiana whilst enr-18-acetoxy-3jS,6a,7a-trihydroxykaur-15-ene (funkiol) and the isomeric 3-acetate (sidofunkiol) were amongst the minor constituents. The selective allylic oxidation of the kaur-16-enes at C-15 by hydrogen peroxide and selenium dioxide is facilitated by the presence of a 7-hydroxy-group. 

Many diterpenes are shown to act as primary antioxidants. Inside the body, some diterpenoids act as primary or synergistic antioxidants [146]. Carotenoids are well known as antioxidant agents and act along two different main pathways physical and chemical radical quenching [147, 148]. Ertas et al. evaluated the antioxidant activity of petroleum ether, methanolic and acetone extracts, and some isolated ent-kaurane diterpenoids from the aerial parts of Sideritis arguta by p-carotene... 

Ertas A, Ozturk M, Boga M, Topcu G (2009) Antioxidant and anticholinesterase activity evaluation of ent-kaurane diterpenoids from Sideritis arguta. J Nat Prod 72 500-502... 

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