Taxinine

Kurono, Masayasu; Nakadaira, Yasuhiro; Onuma, S.; Sasaki, Ko; Nakanishi, Koji

doi:10.1016/s0040-4039(01)90987-6

Cited by 32 publications

(7 citation statements)

References 14 publications

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“…3). This confirms previous structural information of the taxane core where the C-5 and C-12, despite being at opposite ends of the molecule, are neighbors because of the U-shape of the molecule (30).…”

Section: Discussionsupporting

confidence: 90%

CYP725A4 from Yew Catalyzes Complex Structural Rearrangement of Taxa-4(5),11(12)-diene into the Cyclic Ether 5(12)-Oxa-3(11)-cyclotaxane

Rontein

Onillon

Herbette

et al. 2008

Journal of Biological Chemistry

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Taxa-4(5),11(12)-diene is the first committed precursor of functionalized taxanes such as paclitaxel, a successful anticancer drug. Biosynthesis of taxanes in yew involves several oxidations, a number of which have been shown to be catalyzed by cytochrome P-450 oxygenases. Hydroxylation of the C-5␣ of taxa-4(5),11(12)-diene is believed to be the first of these oxidations, and a gene encoding a taxa-4(5),11(12)-diene 5␣-hydroxylase (CYP725A4) was recently described (Jennewein, S., Long, R. M., Williams, R. M., and Croteau, R. (2004) Chem. Biol. 11, 379 -387). In an attempt to produce the early components of the paclitaxel pathway by a metabolic engineering approach, cDNAs encoding taxa-4(5),11(12)-diene synthase and CYP725A4 were introduced in Nicotiana sylvestris for specific expression in trichome cells. Their co-expression did not lead to the production of the expected 5␣-hydroxytaxa-4(20),11(12)-diene. Instead, taxa-4(5),11(12)-diene was quantitatively converted to a novel taxane that was purified and characterized. Its structure was determined by NMR analysis and found to be that of 5(12)-oxa-3(11)-cyclotaxane (OCT) in which the eight-carbon B-ring from taxa-4(5),11(12)-diene is divided into two fused five-carbon rings. In addition, OCT contains an ether bridge linking C-5 and C-12 from opposite sides of the molecule. OCT was also the sole major product obtained after incubation of taxa-4(5),11(12)-diene with NADPH and microsomes prepared from recombinant yeast expressing CYP725A4. The rearrangement of the taxa-4(5),11(12)-diene ring system is thus mediated by CYP725A4 only and does not rely on additional enzymes or factors present in the plant. The complex structure of OCT led us to propose a reaction mechanism involving a sequence of events so far unknown in P-450 catalysis.

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Section: Discussionsupporting

confidence: 90%

CYP725A4 from Yew Catalyzes Complex Structural Rearrangement of Taxa-4(5),11(12)-diene into the Cyclic Ether 5(12)-Oxa-3(11)-cyclotaxane

Rontein

Onillon

Herbette

et al. 2008

Journal of Biological Chemistry

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“…Table 2 lists the mass-to-charge ratio and relative intensities of the T-series ions observed in the EI, CI, and FAB mass spectra. Structural assignments and proposed mechanisms of ion formation are based on low-and high-resolution mass measurements (El, Tables 2 and 3) and product ion CID studies in EI ( Figure 3) and CI (NH 3 ) (Figure 4 Assignment of the m/= 480 peak in the EI spectrum as resulting from the sequence [T-H-AcOH-CO]+' is supported by accurate mass analysis (Table 3) Opening of the taxane ring skeleton of 1 by EI, as reported for taxinol2 [14], was not observed. Fragmentation of 2 is thought to involve scission of the bonds joining the two six-membered rings of the skeleton (C-l/C-2, C-10/C-ll and C-2/C-3, C-9/C-IO), resulting in formation of ions at m rz 135, 137, and 107.…”

mentioning

confidence: 74%

The mass spectrometry of taxol

McClure

Schram

Reimer

1992

J. Am. Soc. Mass Spectrom.

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The antitumor agent taxol has been examined by electron ionization, chemical ionization, and fast atom bombardment mass spectrometry. Three ion series are observed: (1) the M-series, characteristic of the intact molecule; (2) the T-series, with fragments derived from the taxane ring; and (3) the S-series representing the C-13 side chain. Neutral losses dominate each series of ions and serve to verify the presence and number of functionalities in each portion of the molecule. Fragmentation pathways and mechanisms of ion formation are proposed on the basis of product ion analysis and accurate mass measurements.

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“…The diterpene taxinine, 50 , the basic pharmacophore for the antitumor agent taxol, represents another useful application of the CD exciton chirality method. However, the similarity in λ max of the dibenzoates of the 9,10 hydroxyls (230 nm) with the twisted enone of taxinine (274 nm) gave an interaction that led to ambiguous results 82 . Because of this problem, the two hydroxyls were derivatized with red‐shifted chromophores, for example, the julolidine‐based chromophore, 51 , shown below 83 .…”

Section: Resultsmentioning

confidence: 99%

The enduring legacy of Koji Nakanishi's research on bioorganic chemistry and natural products. Part 1: Isolation, structure determination and mode of action

2020

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In this brief review on Koji Nakanishi's remarkable career in natural products chemistry, we have highlighted a number of his accomplishments that illustrate the broad diversity of his interests. These include the isolation, structure determination, and biological mechanism of action of many natural products including the triterpenoid pristimerin; the diterpenoid ginkgolides; insect and crustacean molting hormones; phytoalexins; the toxic red tide principle brevetoxin; the vanadium tunicate pigments; philanthotoxin from killer wasps; antisickling agents; mitomycin DNA adducts; insect antifeedants; a mitotic hormone, the small molecule fish attractants from the sea anemone; new isolation and purification technologies; molecular chemistry of vision; age‐related macular degeneration; and the development of the exciton circular dichroism (CD) chirality method for microscale determination of absolute configuration of natural products and chirality of other chiral molecules and supramolecular assembly.

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Taxinine

Cited by 32 publications

References 14 publications

CYP725A4 from Yew Catalyzes Complex Structural Rearrangement of Taxa-4(5),11(12)-diene into the Cyclic Ether 5(12)-Oxa-3(11)-cyclotaxane

CYP725A4 from Yew Catalyzes Complex Structural Rearrangement of Taxa-4(5),11(12)-diene into the Cyclic Ether 5(12)-Oxa-3(11)-cyclotaxane

The mass spectrometry of taxol

The enduring legacy of Koji Nakanishi's research on bioorganic chemistry and natural products. Part 1: Isolation, structure determination and mode of action

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