14β-Hydroxy-10-deacetylbaccatin III, a new taxane from Himalayan yew (Taxus wallichiana Zucc.)

Appendino, Giovanni; Gariboldi, Pierluigi; Gabetta, Bruno; Pace, Roberto; Bombardelli, Ezio; Viterbo, D.

doi:10.1039/p19920002925

Cited by 62 publications

(44 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, approval of Taxol for the treatment of additional types of cancer, as well as the use of the drug much earlier in the course of intervention, is very likely to increase the demand for Taxol and its precursors for semisynthesis. Additionally, extensive studies on the naturally occurring taxoids, now numbering over 350 (10), have led to the discovery of novel structures and to the preparation of new chemical derivatives with improved biological activity (11)(12)(13)(14). These ''second generation'' taxoid drugs, like Taxol itself, still depend on the isolation of natural products from the yew tree.…”

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

View full text Add to dashboard Cite

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

show abstract

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

View full text Add to dashboard Cite

show abstract

“…The slight differences in the conformations of the benzoyl group at C2 and the acetyl group at C4 were also observed in the crystal structures of other taxanes (Appendino et al, 1992;Gunawardana et al, 1992). However, the side chain at C13 possesses a different conformation from that of taxotere.…”

Section: Commentmentioning

confidence: 70%

2'-Carbamate Taxol

Gao¹,

Golik²

1995

Acta Crystallogr C

View full text Add to dashboard Cite

“…Ring A, 'double-bridged' to the central ring, exhibits the 1,3-diplanar boat conformation with Cll only 0.36 (1) and C15 0.98 (1)A fully above the mean plane of the atoms C13, C12, C14 and C1 [maximum deviation: 0.01 (1)A]. These conformations are more or less identical for all the baccatin derivatives resolved by Xray analysis: baccatin V (Castellano & Hodder, 1973), O-cinnamoyltaxicin-I triacetate (Begley, Frecknall & Pattenden, 1984), 14/3-hydroxy-10-deacetylbaccatin III (Appendino et al, 1992), N-tert-butoxycarbonyl-lOdeacetyl-N-debenzoyltaxol (Gurritte-Voegelein et al, 1990), 9-dihydro-13-acetyl-baccatin III (Gunawardana et al, 1992).…”

Section: Commentmentioning

confidence: 84%