The Taxane Diterpenes

The Taxane Diterpenes.— The taxane skeleton represents an alternative mode of cyclisation of the macrocyclic diterpene hydrocarbon. Seven new taxane derivatives have been isolatedfrom Taxus baccata and characterised on the basis of spectroscopic and other data. Their structures are summarised in the following formulae (136a—g). In addition, the structure of baccatin-III (137), one of a group of complex esters isolated from the same source, has been com-pleted. The application of the olefin Octant rule to the taxane A double bond leads to the absolute configuration of these diterpenes. 

147 a ) p Della Casa de Marcano and T. G. Halsall, Chem. Comm., 1969, 1282 D. P. Della Casa de Marcano, T. G. Halsall, and G. M. Hornby, Chem. Comm., 1970, 216. D. P. Della Casa de Marcano, T. G. Halsall, A. I. Scott, and A. D. Wrixon, Chem. Comm., 1970, 582. 

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A related Diels-Alder reaction offers one approach to the taxane diterpenes. Thus in the presence of (CH,)2A1C1 (3 equiv.) the model compound 3 cyclizes mainly to 4. Even... 

The nickel-catalyzed intramolecular [4 -I- 4] cycloaddition strategy has been successfully applied to the construction of both the ab and bc ring systems of the taxane diterpenes. These studies additionally served to establish the viability of this chemistry for the construction of angularly alkyl-substituted bicy-clo[6.4.0]dodecanes. In an example typical of this class of transformatiais (Scheme 16), cyclooctadiene (125) was produced with greater than 97% diastereoselectivity and in 92% chemical yield when tetraene... 

Harriman GCB, Jalluri RK, Grunewald GL, Vander Velde DG, Georg GI (1995) The Chemistry of the Taxane Diterpene Stereoselective Synthesis of 10-Deacetoxy-... 

Magnus and coworker have presented a new strategy for the preparadon of taxane diterpenes by using nitro-aldol reacdon and denitradon as key steps fsee Scheme 11 ... 

Entries 10 to 14 show reactions involving acetals. Interestingly, Entry 10 shows much-reduced stereoselectivity compared to the corresponding reaction of the aldehyde (The BF3-catalyzed reaction of the aldehyde is reported to be 24 1 in favor of the anti product ref. 80, p. 91). There are no stereochemical issues in Entries 11 or 12. Entry 13, involving two cyclic reactants, gave a 2 1 mixture of stereoisomers. Entry Mis a step in a synthesis directed toward the taxane group of diterpenes. Four stereoisomeric products were produced, including the Z E isomers at the new enone double bond. 

This reaction can be used in synthesis of medium-sized rings by cleavage of specific bonds. An example of this reaction pattern can be seen in a fragmentation used to construct the ring structure found in the taxane group of diterpenes. 

Cycloadditions of bisdienes. This reaction, catalyzed efficiently by Ni(COD)2-P(C6Hs)3 (usually 1 2), provides a useful route to the eight-membered ring system found in taxane diterpenes. 

The metabolism of taxol by Eucalyptus perriniana cell suspension cultures has been recently reported to induce hydrolyses of ester bonds at C-13, C-10 and C-2 [222]. At this moment only 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 Nocar-dioides albus SC13,911 and N. luteus SC13,912, respectively, have been reported [223]. On the other hand, Hu et al. [224-226] have recently described some fungal biotransformations of related natural taxane diterpenes extracted from Chinese yews or their cell cultures, in order to obtain new active substances or precursors for hemisynthesis. The taxadiene 145, a 14 -acetylated derivative... 

Overall, however, the immensity of temperate land corresponds to a most various secondary metabolic production, different from that of tropical land. The most renowned alkaloids belong to the morphine class (Chart 6.2.A1), and, in combination with isoprenoids, to the ergot and triterpene classes (Chart 6.2. A2). Prominent in the peptides are the cyclosporins (the first of which was isolated from a fiingus collected in Norway), streptogramins, and P-lactams (Chart 6.2.P). The isoprenoids are represented by pyrethrin monoterpenes, cedrane sesquiterpenes, ginkgolide and taxane diterpenes, ophiobolane sesterterpenes, and arborane and amyrin-like triterpenes (Chart 6.2.1). In the polyketides, epothilones, recently discovered from Myxobacteria, and the long known rapamycin, are two prominent classes of macrolides (Chart 6.2.FA/PO/C). 

The taxanes are a group of polycyclic diterpenes produced by various species of trees (such as yew) and are most commonly known as the potent anticancer drug paclitaxel (Taxol). The extraction process is costly. 

It is generally agreed that mevalonate is the precursor to sterols in higher plants as well as in animals and is also the precursor to plant carotenoids. However, it is poorly incorporated into monoterpenes and into some diterpenes such as those of the taxane group.26 27 The alternative glyceraldehyde 3-... 

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

The macrocylic diterpene alcohol, verticillol (3) was isolated from the wood of Sciadopitys verticillata Sieb. Et zucc. (Taxodiaceae) [13]. The structure of verticillol (3) was elucidated from NMR-LIS studies on it as well as its correlation to the diepoxide (14) whose structure was established by direct single crystal X-ray analysis. The absolute configuration of verticillol (3) was determined by CD data of the verticillol norketodiepoxide (15). The carbocyclic framework of verticillol (3) is somewhat akin to at of cleomeolide (1). However, the presence of the substituents(3-OH and C-8—>C-4 lactone) in appropriate positions in (1) facilitates its conversion to compounds analogous to taxane diterpenes. 

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