Taxus brevifolia diterpenes

One of the simplest and most significant of the diterpenes is phytol, a reduced form of geranylgeraniol, which constitutes the lipophilic side-chain of the chlorophylls. Phytol also forms a part of vitamin E (tocopherols) and K molecules. Vitamin A is also a 20-carbon-containing compound, and can be regarded as a diterpene. However, vitamin A is formed from a cleavage of a tetraterpene. Among the medicinally important diterpenes, paclitaxel, isolated from Taxus brevifolia (family Taxaceae), is one of the most successful anticancer drugs of modern time. 

Taxol (1), Fig (6), is another important diterpene with anticancer properties. It was isolated in 1971 from Taxus brevifolia Nutt. (Taxaceae), which is a slow growing shrub/tree, found in the forests of N.W Canada and USA. Taxol is one of over one hundred taxanes, which have been... 

To date over 30 plant terpenoid synthases have been cloned as cDNAs, and many of these were found to encode enzymes of secondary metabolism (43). Isolation and analysis of six genomic clones encoding monoterpene ((—)-pinene and (—)-limonene), sesquiterpene ((E)-a-bisabolene and S-selinene) and diterpene (abietadiene) synthases from Abies grandis, and a diterpene (taxadiene) synthase from Taxus brevifolia have been reported (44). Overexpression of a cotton farnesyl diphosphate synthase (EPPS) in transgenic Artemesia annua has resulted in 3- to 4-fold increase in the yield of the sesquiterpenoid anti-malarial drug, artemisinin, in hairy roots (45). 

Taxol (paclitaxel) (Bl), a taxane diterpene isolated from the bark of the Pacific yew tree Taxus brevifolia Nutt. (Taxaceae family). 

The diterpene taxol is used as a potent chemotherapeutic agent in cancer treatment. The hmited supply of the drug from the natural source, the bark of the Pacific Yew (Taxus brevifolia), was overcome by a semisynthetic approach. Taxol is presently manufactured by coupling the advanced naturally occurring taxoid 10-deacetylbaccatin 111, isolated from needles of the more abundant Tdxus baccata, to a synthetic side-chain precursor. 

Epothilones A and B are promising anticancer agents that bind to microtubules in the cell in the same way that paclitaxel (Taxol) does and are more potent.410 Paclitaxel was obtained first from the bark of the Pacific yew (Taxus brevifolia).4n Widespread extraction of the compound from this source could have wiped out the species. Fortunately, it can now be extracted from the needles of more common yews or produced in tissue culture. (See Sec II.C on tissue culture.) Forskolin is a diterpene, from the roots of Coleus forskohlii, that lowers blood pressure.412 Him-bacine, from an Australian pine tree, offers a potential treatment for Alzheimer s disease.413 Combretastatin, from the bark of the African bush willow, Combretum caffrum, cuts the flow of blood to tumors, causing 95% of the cancer cells to die in 24 h, but does not harm healthy blood vessels.414... 

Oxetanes rarely occur in nature. The diterpene alcohol taxol (paclitaxel ) was isolated in 1971 from the bark of the pacific yew tree (Taxus brevifolia) native to the northwest USA, and its structure elucidated. The compound, which is now marketed, contains an oxetane ring and displays a strong antitumour and antileukaemia activity. Its total synthesis has been achieved [5]. 

Taxanes are diterpene compounds containing a taxane skeleton. Paclitaxel, the first compound identified with a taxane ring, was isolated from the bark of the pacific yew, Taxus brevifolia in 1971. Subsequently, paclitaxel and tax-oid derivatives have been reported from the foliage and bark of several other species of Taxus, like T. wallichinan, T. baccata, T. canadensis, T. cuspidata, and T. Yunnanensis In addition to the plant resources, some endophytic fungi, such as Tubercularia sp., Sporormia minima and Seimatoantlerium tepui-ense, have also been reported to produce paclitaxel and other taxoids. " Paclitaxel is effective for the treatment of leukemia and cancers. It has been reported that paclitaxel is capable of curing approximately 30%, 50%, and 20% of ovarian, breast, and lung cancer patients, respectively. ... 

Taxol is a complex diterpene from the yew tree, especially the Pacific yew—Taxus brevifolia (Taxaceae). Taxol and its derivatives are used as prescription drugs for cervical and breast tumours (Lenaz and De Furia 1993). It has an antimitotic effect, associated with an interaction of taxol with the tubulin-microtubule system (Hamburger and Hostettmann 1991). 

The abietadiene synthase from fir was purified and internal amino-acid sequence information was employed to isolate the corresponding clone from a wound-induced stem cDNA library [147]. The cDNA encodes an 868 residue protein (99,536 Da) bearing a plastidial transit peptide and exhibiting the greatest sequence similarity to the only other known gymnosperm diterpene cyclase, taxadiene synthase from Taxus brevifolia [130]. Preliminary studies have identified a highly active truncation starting at V85 which approximates the preprotein-mature protein junction. 

Paclitaxel, a natural diterpene alkaloid, was originally isolated from the bark of the Taxus brevifolia tree in the western region of the United States. It has high lipophilidty, low water solubility high protein binding rate and mainly disturbs the structure of the inner part of the cell membrane [134]. 

A diterpene alkaloid, initially isolated from the bark of the pacific yew Taxus brevifolia, has 11 chiral centers so the number of possible diastereoisomers exceeds 2000. An important chemotherapeutic agent. Lack of adequate supply from natural sources and chirality of the molecule were the reasons for the development of a semi-synthetic conversion from baccat-ins, which are relatively abundant in other yew species whereas full synthesis is multistep and costly [55,56],... 

Paclitaxel (Taxol) 57, a natural terpenoid product derived from the bark of the Pacific yew Taxus brevifolia [83-85], and its hemisynthetic analog docetaxel (Taxotere) 58, are two recently discovered promising antitumor agents. At this moment, very few data have been published about the microbial metabolism of taxoid compounds only site-specific hydrolyses of acyl side chains at C-13 or C-10 by extracellular and intracellular esterases of Nocardioides albus SC 13911 and N. lutea SC 13912, respectively, have been reported [86]. On the other hand, Hu et al. [87-89] recently described some fungal biotransformations of related more abundant natural taxane diterpenes extracted from Chinese yews or their cell cultures, in order to obtain new active substances or precursors for hemisyn-thesis of paclitaxel analogs. 

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