Enantioselective Total Synthesis of Taxol

Morihira, Koichiro; Hara, Ryujiro; Kawahara, Shun‐ichi; Nishimori, Toshiyuki; Nakamura, Nobuhito; Kusama, Hiroyuki; Kuwajima, Isao

doi:10.1021/ja9824932

Cited by 180 publications

(61 citation statements)

References 16 publications

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“…These ''second generation'' taxoid drugs, like Taxol itself, still depend on the isolation of natural products from the yew tree. Several elegant total synthetic routes to Taxol and related taxoids have been developed (15)(16)(17)(18)(19)(20); however, low yields and high costs preclude them from commercial production (21) and, for the foreseeable future, sourcing must continue to rely on Taxus species or, potentially, cell cultures derived therefrom (6). Improved biological production methods depend on an understanding of the biosynthetic pathways leading to Taxol and related taxoids and definition of the responsible enzymes and genes.…”

mentioning

confidence: 99%

Taxol biosynthesis: Taxane 13α-hydroxylase is a cytochrome P450-dependent monooxygenase

Jennewein

Rithner

Williams

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

201

126

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A central feature in the biosynthesis of Taxol is oxygenation at multiple positions of the taxane core structure, reactions that are considered to be mediated by cytochrome P450-dependent monooxygenases. A PCR-based differential display-cloning approach, using Taxus (yew) cells induced for Taxol production, yielded a family of related cytochrome P450 genes, one of which was assigned as a taxane 10␤-hydroxylase by functional expression in yeast. The acquired clones that did not function in yeast were heterologously expressed by using the Spodoptera fugiperdabaculovirus-based system and were screened for catalytic capability by using taxa-4(20),11(12)-dien-5␣-ol and its acetate ester as test substrates. This approach allowed identification of one of the cytochrome P450 clones (which bore 63% deduced sequence identity to the aforementioned taxane 10␤-hydroxylase) as a taxane 13␣-hydroxylase by chromatographic and spectrometric characterization of the corresponding recombinant enzyme product. The demonstration of a second relevant hydroxylase from the induced family of cytochrome P450 genes validates this strategy for elucidating the oxygenation steps of taxane diterpenoid (taxoid) metabolism. Additionally, substrate specificity studies with the available cytochrome P450 hydroxylases now indicate that there is likely more than one biosynthetic route to Taxol in yew species.paclitaxel ͉ taxa-4(20),11(12)-dien-5␣,13␣-diol ͉ Taxus cuspidata ͉ yew

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mentioning

confidence: 99%

Taxol biosynthesis: Taxane 13α-hydroxylase is a cytochrome P450-dependent monooxygenase

Jennewein

Rithner

Williams

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

201

126

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“…To date, seven methods was used in description the total synthesis of taxol [94][95][96][97][98][99][100][101][102][103]. Nicolaou and his co-workers were reported total synthesis of taxol and in 1994 [104][105][106][107].…”

Section: Oxetane As Building Blocks For Synthesis Of Taxolmentioning

confidence: 99%

Oxetanes as versatile building blocks in the total synthesis of natural products: An overview

Mahal

2015

Eur. J. Chem.

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“…The problem was solved by the development of semisynthetic approaches to paclitaxel from (2R,3S)-phenylisoserine and a naturally occurring compound, 10-deacetylbaccatin III (DAB; Figure 6.17) isolated from a renewable source: leaves of the common yew (Taxus baccata) [223]. Several total syntheses of paclitaxel have been reported [224][225][226][227][228][229][230][231][232]. Despite the fact they are state-of-the-art organic chemistry, they are highly laborious, time-consuming and cost-ineffective, and hence completely unattractive as a competitive source of this antitumor agent.…”

Section: Paclitaxel and Its Derivativesmentioning

confidence: 99%