Taxus synthesis

Since the discovery of the high anticancer activity of taxol, much attention has been drawn to its asymmetric synthesis. The total synthesis stood for more than 20 years as a challenge for organic chemists. The compound taxoids are diterpenoids isolated from Taxus species and have a highly oxidized tricyclic carbon framework consisting of a central eight-membered and two peripheral six-membered rings (see Fig. 7-2).21... 

A fine example of such a semi-synthesis is the preparation of the anti-cancer drug paclitaxel (Taxol ), a relatively scarce compound from Taxus brevifolia. Here, the natural and better accessible 10-deacetylbaccatin III, isolated from the leaves of Taxus baccata, provides the complicated ring system of paclitaxel, including all substituents with the right stereostructure (Scheme 5.1). In just four reaction steps [5] paclitaxel is obtained from 10-deacetylbaccatin III. 

Paclitaxel (21) was originally obtained from the bark of the Pacific yew, Taxus brevifolia Nutt. However, as the tree takes 200 years to mature, stripping the bark to produce this compound for the market was not sustainable. A better source of naturally occurring paclitaxel has not been found in other species and the total synthesis, on the other hand,... 

Keywords Biological Activity Biosynthesis Lignans Synthesis Taxaceae Taxus... 

A stereocontrolled synthesis of the biologically active neolignan (+)-dehydrodiconiferyl alcohol, which was isolated from several Taxus species, was achieved via Evans asymmetric aldol condensation [58] using ferulic acid amide derived from D-phenylalanine. The reaction steps are shown in Fig. 9. This stereocontrolled reaction is also useful for preparing the enantiomer of (+)-dehydroconiferyl alcohol using chiral auxiliary oxazolidinone prepared from L-phenylalanine. This reaction also enables the syntheses of other natural products that possess the same phenylcoumaran framework. 

It has been estimated that six 6-inch-diameter trees would have to be sacrificed for enough Taxol to treat one woman suffering from ovarian cancer. Considering that the number of potential patients in the late 1980s numbered approximately 12,000, an eventual limitation of Taxol was possible. Fortunately, the problem was solved in the early 1990s by the partial synthesis of Taxol from a precursor produced in needles and twigs from the more renewable Taxus baccata. 

Elicitation is effective in enhancing metabolite synthesis in some cases, such as in production of paclitaxel by Taxus cell suspension cultures [2] and tropane alkaloid production by suspension cultures of Datura stramonium [3]. Increasing the activity of metabolic pathways by elicitation, in conjunction with end-product removal and accumulation in an extractive phase, has proven to be a very successful strategy for increasing metabolite productivity [4]. For example, two-phase operation with elicitation-enhanced alkaloid production in cell suspension cultures of Escherichia californica [5,6]. 

The synthetic principle of olefinating an a,co-bisfunctional synthon A, representing the later molecular centre of the carotenoid, with two reaction partners B, the future molecular ends, can easily be described by the equation A + 2B -> B—A—B. This method was used by Mayer et al.265> in the synthesis of rhodoxanthin 550, a ketonic carotenoid, which was isolated for the first time from the red berrys of the yew-tree Taxus baccata. The authors describe the conversion of two equivalents of the stable phosphorane 548 with one equivalent of the C12-dialdehyde 549 265) (Scheme 93). The analogous reaction of crocetindial 552 with substituted benzylidenephospho-ranes such as 551 gives carotenoids such as isorenieratene 553266,267) and related compounds 266> (Scheme 93). Condensation of the phosphoranes 554 and 555 with the Cjo-dialdehyde 539 yields carotenoids of the dihydro type 556 268) and such like 557 269), respectively (Scheme 93). 

Pandey, R. C. Yankov, L. K. Poulev, A. Nair, R. Caccamese, S. Synthesis and separation of potential anticancer active dihalocephalomannine diastereomers from extracts of Taxus yunnanensis. J. Nat. Prod., 1998, 61 57-63. 

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