Preface to the series

There is increasing interest in industry, academia and the health sciences in medicinal and aromatic plants. In passing from plant production to the eventual product used by the public, many sciences are involved. This series brings together information which is currently scattered through an ever increasing number of journals. Each volume gives an in-depth look at one plant genus, about which an area specialist has assembled information ranging from the production of the plant to market trends...

Hydroxyl Group Or Acetate At C5

Although brevifoliol was previously assigned as a normal structure, it was reassigned as a member of this class by Appendino et al. (1993c,d). A brevifoliol type taxoid (13b) was isolated from T brevifolia (Chen et al, 1994). Two taxoids with a basic skeleton (13c, 13i) were isolated from T chinensis (Fuji et al, 1992). The structures of taxchinins D and G have been determined as 13g and 13l by Tanaka et al. (1994). Large-scale processing of the chloroform extract of the bark of T brevifolia by...

An alternate stereochemical nomenclature for taxane skeleton

Since Wall, Wani, and McPhail first disclosed the structure of taxol in 1971 (Wani et al., 1971), numerous reports about taxoids have appeared in the literature. The geminal dimethyl groups at C-15 were first numbered as C-19 and C-20 as seen in structure 1a (Figure 1.4). Later, the numbering was changed to C-16 and C-17, which is the currently accepted numbering shown in the IUPAC recommendation for the unbridged taxane skeleton (1b) (IUPAC, 1999). Other structures have been seen and discussed...

An Opened Oxetane Ring

Two 11(15 1) abeotaxoids (14e and 15b) were isolated from T. yunnanensis by Zhou et al. (1995). A taxoid (10-4c) and two abeotaxoids (15c and 15e) were isolated from the twigs of T. mairei (Yang et al, 1999). Yunantaxusin A (15f), an 11(15 1)abeo taxane-type diterpene with an opened oxetane ring, has been isolated from the leaves and stems of T. yunnanensis (Zhang et al, 1994) (Figure 3.47). From T. chinensis var. mairei 16a was isolated by Shi et al. (1999). Taxuchinin A (16b) was isolated...

B

Nuclear Magnetic Resonance spectroscopy 1H-NMR spectroscopy Nuclear Magnetic Resonance spectroscopy (NMR) is an important method for elucidating the structures of various compounds via instrumental analysis. Studies of the 'H-NMR spectra of taxoids were well reviewed by Miller (1980) and Kingston et al. (1993). As taxol has been the most representative taxoid, it must be discussed as a primary example. Detailed studies at 500 MHz have provided the most complete analysis of the spectrum...

Benzoyl transferase from Taxus

Recently, Walker and Croteau isolated a cDNA clone encoding a taxane 2a-O-benzoyltransferase from Taxus cuspidata (Walker and Croteau, 2000). The proposed outline of the taxol biosynthetic pathway about the cyclization of GGPP to taxadiene by taxadiene synthase and the hydroxyla-tion to taxadien-5a-ol by taxadiene 5 a-hydroxylase is shown in Figure 2.9 (a) the acetylation of taxadiene-5a-ol by taxa-4(20),11(12)-dien-5a-ol O-acetyltransferase (TAT) (b) the conversion of a 2-debenzoyl taxoid-type...

C11 Hydroxylated Or C10 Ketonized Group

Taxezopidine K (1-1'b) was isolated from the seeds of the Japanese yew T cuspidata (Shigemori et al, 1999). Taxuspine P (1-1'a) (Kobayashi et al, 1996) and Taxuspine D (1-1'c) (Kobayashi et al, 1995a) were isolated from stems of the Japanese yew T. cuspidata (Figure 3.5). 2a-Benzoyloxy-9a,10 -diacetoxy-1 2a-Benzoyloxy-10 ,13a-diacetoxy-1 R4 R5 R6 Plant source References H H H T. chinensis Jia et al. (1991) Ac Ac H T. chinensis Jia et al. (1991) H Ac Ac T. chinensis Jia et al. (1991) H H 7...

C13 Ketonized Group

One more type of this group is ketonized at C-13 as shown in Figure 3.6. Taxinine A (1-2a) and taxinine H (1-2b) were isolated from T. cuspidata and T. chinensis (Chiang et al, 1967). Taxuspine F (1-2c) and G (1-2d) were isolated from the Japanese yew T. cuspidata (Kobayashi et al, 1995b). Taxezopine C (1-2f) and D (1-2g) were isolated from the Japanese yew (Wang et al., 1998). Deacetyltaxinine A(1-2d) was isolated from the needles and stems of the Chinese yew T. cuspidata with two other...

Capillary Ion Electrophoresis And Capillary Electrochromatography

Capillary electrophoresis (CE) is a rapid separation technique that operates on the basis of the different migration of charged and uncharged species in an electric field. CE can also be combined with other processes to provide high separation efficiency and selectivity with low solvent consumption and operation costs. Capillary ion electrophoresis (CIE) combines CE with an osmotic flow modifier and indirect UV detection and capillary electrochromatography (CEC) combines CE with HPLC. Nair et...

Ch3

Chinennsis var. mairei (cell cult.) T. yunnanensis 7. chinennsis var. mairei (cell cult.) 7. chinennsis var. mairei (cell cult.) T. brevifolia Zhang et al. (1994a) Ma et al. (1994b) 4g OAc OAc butyryloxy-4(20),11-taxadiene OCOCHCH2CH3 7. chinennsis var. mairei Ma et al. (1994b)

Characteristics of Taxus species

The classification of Taxus tree species by Kr ssmann (1983) is shown in Table 6.1. Taxol is contained in Taxus species other than Taxus brevifolia Nutt (Pacific yew), such as Taxus cuspidata Sieb. et Zucc. (Ohira et al, 1996) and Taxus cuspidata var. nana Rehd (Tachibana et al, 1995), which also grow in Japan. Taxus cuspidata, or Japanese yew, is an evergreen arbor and grows in temperate and subarctic forests in Hokkaido, Honshu, Shikoku, and Kyushu, and in polar forests in Sakhalin and the...

Cinnamoyl Or Aminoacyl Group At C5

Taxuspine A (13-3f) was isolated from the stems of Japanese yew T. cuspidata (Kobayashi et al, 1994). The structures of taxchinin E (13-3g), H (13-3d), I (14-1h), J (14-2b), K (14m), taxchin A (1-4c) and taxchin B (1-6a), isolated from T. chinensis, have been elucidated by means of NMR spectroscopy. The first five possess a rearranged taxoid skeleton, and the rest have an ordinary taxane framework (Tanaka et al., 1994). Taxuspine M (13-3a) was isolated from the stems of the Japanese yew T....

Conclusion

Improving the production of taxol or taxoid for drug semi-synthesis (Nicolau et al., 1994) should be achieved by a thorough understanding of the complex biosynthesis pathway and its rate limiting steps. A systematic approach should reveal the sequence of oxygenation and acyla-tion steps, the timing of the C-9 hydroxy dehydrogenation and the unique oxetane ring formation, and the coordination of these processes with the assembly of the N-benzoyl phenylisoserine side-chain (Fleming et al, 1994...

Drying temperature C

Figure 6.13 Effect of drying temperature on the extract yield from the needles and bark of T. cuspidata. Notes * Average percentages of 5 samples based on the oven-dried material. ** Control, fresh frozen samples. Figure 6.13 Effect of drying temperature on the extract yield from the needles and bark of T. cuspidata. Notes * Average percentages of 5 samples based on the oven-dried material. ** Control, fresh frozen samples.

Earlier studies of taxol biosynthesis

The structure of taxol is quite complex and bears an unusual diterpene carbon skeleton, eight oxy-functional groups, and an assortment of appended acyl side-chains, for a total of 11 chiral centers (Wani et al., 1971) (Figures 2.2(a,b)). As proposed first by Harrison et al. (1966), a proposal for taxol biosynthesis posited the initial formation of an olefinic taxane skeleton, followed by a series of oxygenation steps and, ultimately, acylation reactions (Zamir et al., 1992 Eisenreich et al.,...

Extraction separation and purification procedures

Extraction, separation, and purification procedures for taxoids have been discussed in numerous reports, including comprehensive excellent reviews by Snader (1995) and Theodoridis and Verpoorte (1996). Examples of these procedures will be given briefly below. For more details in this research area, refer to the reviews indicated above and literature cited therein. * Taxol is a registered trademark of Bristol-Myers Squibb Company and the generic name of the drug is paclitaxel. However, in this...

Nbu

T. chinensis var. mairei Shi et al. (1999g) T. chinensis var. mairei Shi et al. (1999g) Zhang et al. (1994a) Zhang et al. (1994b) Figure 3.48 Taxoids with an C-4(20) epoxide. Structures of 2(3 - 20)-abeotaxoids with a C-4(20) double bond Two taxoids (17a and 17c) were isolated from T. x media by Rao et al. (1996). Two rearranged taxoids, taxin B (17d), and 2-deacetyltaxin B (17b), were isolated from T. yunnanensis (Yue et al, 1995c). Three taxoids were isolated from the bark of the Chinese yew,...

Nxo

Figure 3.23 Cinnamoyl or aminoacyl group at C-5. 2003 Taylor & Francis A hydroxyl group or acetyl group at C-5 Two taxoids were isolated from the needles of T chinensis and their structures were established as 2a, 5a, 9a-trihydroxy-10p, 13a-diacetoxy-4p, 20-epoxy-taxa-11-ene (9c) and 2a, 5a, 9a (1m) (Zhang, Z.P. et al., 1995). An epoxide (9-1a) was isolated from T. wallichiana (De Marcano and Halsall, 1970). Spectroscopic reexamination of brevifoliol indicated its structure must be revised...

Info

Numbers in parenthesis after compounds names are the numbers used in Chapter 3-Measured in CDO3, 8 values with TMS as internal standard-Multiplicity s singlet, d doublet, t triplet, q quartet. Numbers in parenthesis after compounds names are the numbers used in Chapter 3-Measured in CDO3, 8 values with TMS as internal standard-Multiplicity s singlet, d doublet, t triplet, q quartet.

Introduction

The natural product diterpenoid taxol is regarded as one of the most useful anticancer drugs of plant origin available today (Suffness, 1995). Taxol is effective in the treatment of ovarian and breast cancer, and shows promise for various other cancers, such as head and neck, lung, gastrointestinal, and bladder (Holmes et al., 1995 Suffness, 1995). The fundamental anticancer mechanism of taxol is quite novel and unique. In contrast to Vinca alkaloids, colchicine, and other antitumor agents that...

Kind of solvent

Figure 6.17 Decrease of taxol with time in various solvents. Figure 6.17 Decrease of taxol with time in various solvents. * Percentages of 3 samples based on oven-dried material. MeOH, methanol EtOAc, ethylacetate EtOH, ethanol MeCN, acetonitril M D, MeOH dichloromethane (1 1, v v) D, dichloromethane. Figure 6.18 Schematic diagram of Supercritical Fluid Extraction (SFE). Figure 6.18 Schematic diagram of Supercritical Fluid Extraction (SFE). We used a supercritical fluid extractor (Thermo...

N

This group of taxoids is worthy of notice, because it includes taxol and its potential semisynthetic precursors baccatin III and 10-deacetylbaccatin III. Simple taxoids of this group are illustrated in Figures 3.25 3.35. All members isolated to date are highly oxygenated, with oxygen substituents at C-2, C-4, C-7, C-9, C-10, and C-13. Even the C-1 position, which is normally not oxygenated in the other series of compounds, is usually oxygenated in this series. Taxoids with both an oxetane ring...

O

13a-triacetoxy-2(3 20)abeotaxa-2a-ol-4(20),11-dien-9-one (17-1c), 5a-cinnamoyloxy-10 ,13a-diacetoxy-2 (3 20) (17-1d), (3 20) abeotaxa-4(20),11-dien-9-one (17-1e), 7-O-acetyltaxine A (17-2c), 2a, 7 , 10 , 20) abeotaxa-4(20),11-dien-9-one (17-2d), 5-O-acetyl- taxinine M (7i), 5a-hydroxy-2a,7 ,10 , 13a-tetraacetoxy-2(3 20)abeotaxa-4(20),11-dien-9-one (17d), and 2-deacetyltaxine B (17b), on the basis of 1D and 2D NMR spectroscopic analysis. Compound 1, as a new one isolated from T. chinensis var....

Or3

Plant source T. chinensis T. canadensis References Tanaka et al. (1994) Zamir et al. (1999) Figure 3.8 Oxetane or epoxide ring opened group. cinnamoyl group at C-5. Moreover, the taxoid (1-6a) also has a cinnamoyl group at C-5 and a double bond at C-4(5) (Figures 3.7 and 3.8). Taxoids with an amino acyl group at C-5 AMINOACYL GROUP Taxane-type alkaloids (2a-f, 3a-c) possessing a similar side-chain at position 5 were identified from Austrotaxus by Ettouati et al. in 1988 89. Eighteen taxane-type...

Oxetane Or Epoxide Ring Opened Group

One (1-3a) of the six taxane diterpenoids is a new taxoid isolated from T chinensis var. mairei, and is a rare example of a taxoid with a 4,11 double bond in this class (Shi et al, 1999). Taxezopidine B (1-3b) was isolated from T cuspidata by Wang et al. (1998). Two taxoids (1-4a, 1-4b) were isolated from T mairei (Liang and Kingston, 1993). Taxchin A (1-4c) was isolated from T chinensis by Tanaka et al. (1994). Taxumairol A (1-4d) was isolated from T mairei (Shen et al, 1996). Two novel...

P450

Recombinant enzyme thereby confirmed the conversion of GGPP to taxadiene. The DNA sequence has an open reading frame of 2586 nucleotides, and the deduced polypeptide consists of 862 amino acid residues corresponding to a molecular weight of about 98,000. It contains a long plastidial targeting signal sequence at the N-terminal. Sequence comparison with other terpenoid synthases of higher plant origin showed a significant homology, especially with abi-etadiene synthase of gymnosperm origin,...

Physical methods for identification of the structures of taxoids

Although NMR spectroscopy is generally considered the most useful method for the structural elucidation of taxoids, other instrumental spectroscopic techniques add unique and confirmatory data. The UV spectra of taxoids containing only a ring A enone system display an anomalously long wavelength absorption band. Kingston et al. (1993) summarized about these spectroscopy. The overall ring strain of the taxane skeleton is, however, the major factor and this factor is apparent in the spectrum of...

R

Plant source T. cuspidata T. chinensis T. x media T. cuspidata T. x media T. cuspidata (Japan) T. cuspidata T. cuspidata (Japan) T. cuspidata (Japan) T. cuspidata (Japan) Chiang et al. (1967) Chiang et al. (l975) Rao et al. (1996) Chiang et al. (1967) Rao et al. (1996) Tong et al. (1995) Kobayashi et al. (1995b) Morita et al. (1998a) Barboni et al. (1995b) Barboni et al. (1995b) 11-dien-13-one 11-dien-13-one T. chinensis var. mairei Shi et al. (1999d) T. yunnanensis Shi et al. (1999d)

References

Alden, C.L., Fosnaugh, C.J., Smith, J.B., and Mohan, R. (1977) Japanese yew poisoning of large domestic animals in the midwest. J. Am. Vet. Med. Assn., 170, 314. Auriola, S.O.K., Lepisto, A.-M., Naaranlajoki, S.P. (1992) Determination of taxol by high-performance liquid chromatography-thermospray mass spectrometry. J. Chromatogr., 594, 153. Baloglu, E. and Kingston, D.G.I. (1999) The taxane diterpenoids. J. Nat. Prod., 62, 1448-1472. Blechert, S. and Guenard, D. (1990) Taxus Alkaloids in The...

Subsequent oxygenation steps

Subsequent reactions in the taxol biosynthesis pathway include additional hydroxylations, acylations on the hydroxy groups, oxidation of hydroxyl into carbonyl, and the generation of the oxetane ring system. Numerous naturally occurring taxoids exhibit a broad range of oxygenation and acylation patterns, which provide no rigid guidance in predicting the order of functional-ization beyond taxa-4(20).11(12)-dien-5a-yl acetate. Proposed sequence for the hydroxylation of taxa-4(5), 11(12)-diene to...

Taxus

Taylor & Francis Croup LONDON AND NEW YORK First published 2003 by Taylor & Francis Simultaneously published in the USA and Canada 29 West 35th Street, New York, NY 10001 Taylor and Francis is an imprint oof the Taylor & Francis Group This edition published in the Taylor & Francis e-Library, 2003. All rights reserved. No part of this book may be reprinted or reproduced or utilised in any form or by any electronic, mechanical, or other means, now known or hereafter invented,...

The moisture content of the needles was 5089 at 24h 2399 at 48h and 1059 at 192h Because we had pulverized the

Figure 6.12 Taxol content in the needles and bark of T. cuspidata. Note * Percentages based on oven-dried material. Bars show means SD. Figure 6.12 Taxol content in the needles and bark of T. cuspidata. Note * Percentages based on oven-dried material. Bars show means SD. not contaminated by fungi during one year of storage. It has been reported that fungi grow on the leaves of Crotow sublyratus unless their water content is reduced below 10 (Ichikawa, 1996). Accordingly, reduction of water...

The third step in taxol biosynthesis acetylation of taxadienol and oxetane ring formation

Most naturally occurring taxoids are acetylated, or otherwise acylated, at C-5 (Kingston et al., 1993 Baloglu and Kingston, 1999). This suggests that the Acylation of taxa-4(20),11(12)-dien-5a-ol could be the third step in taxol biosynthesis. Additionally, the 4(20)-ene-5a-acetate functional group should play a crucial role in the elaboration of the oxetane ring by a mechanism involving epoxidation of the 4(20)-double bond, followed by intramolecular acetoxy migration associated with epoxide...

Yoshinari Kikuchi And Mitsuyoshi Yatagai

7 Analytical aspects of taxoids MUTSUO KOZUKA, SUSAN MORRIS-NATSCHKE, AND KUO-HSIUNG LEE 8 Chemistry of taxol and related taxoids HUI-KANG WANG, HIRONORI OHTSU, AND HIDEJI ITOKAWA ZHIYAN XIAO, HIDEJI ITOKAWA, AND KUO-HSIUNG LEE 10 Structure activity relationships of taxoids XIHONG WANG, HIDEJI ITOKAWA, AND KUO-HSIUNG LEE 11 Preclinical and clinical studies of the taxanes

The authors would like to thank Dr K Hayashi for his valuable suggestions References

Altstadt, T.J., Gao, Q., Wittman, M.D., Kadow, J.F., and Vyas, D.M. (1998) Crystallographic determination of the stereochemistry of C-6,7 epoxy paclitaxel, Tetrahed., Lett., 39 (28), 4965 4966. Appendino, G., Gariboldi, P., Gabetta, B., Pace, R., Bombardelli, E., and Viterbo, D. (1992a) 14-Hydroxy-10-deacetylbaccatin III, a new taxane from Himalayan yew (Taxus wallichiana Zucc.). J. Chem. Soc. Perkin Trans. I, 2925 2929. Appendino, G., Lusso, P., Gariboldi, P., Bombardelli, E., and Gabetta, B....

Miscellaneous Ether Linkage Group

The needles of T. wallichiana gave the novel oxetane-type diterpenoids (10-6b and 14-4a) (Appendino et al., 1993e). Two taxoid diterpenoids, taxayunnanine E (14-5a) and Figure 3.46 Taxoids with miscellaneous ether linkage group. Figure 3.46 Taxoids with miscellaneous ether linkage group. taxayunnansin A (14i) were isolated from T. yunnanensis (Zhang et al., 1995). Wallifoliol (14-6a) was isolated with known taxoids (taxol, cephalomannine, 10-deacetylbaccatin III, brevifoliol,...

Approaches to Taxus plant tissue culture

In the 1950s, La Rue (1953) and Tulecke (1959) initiated approaches to Taxus plant cell and tissue culture. At present, the production capability of taxol and related taxanes using cell and tissue culture has been established and the conditions suitable for fast-growing cultures to produce high levels of taxol have been studied in commercial production. Callus and cell suspension cultures have been established from T. brevifolia (Christen et al, 1989, 1991 Wickremesinhe, 1992 Wickremesinhe and...

Extraction

Taxoids were extracted from the specimen (whole seedlings) with five volumes of n-hexane for 24 h. The solvent was removed and the insoluble residue was then extracted with ten volumes of methanol for 48 h. The solution was condensed at 50 C, and 76.45 g of the methanol extract was obtained. The methanol extract was further separated with three volumes of ethyl acetate and three volumes of distilled water. The ethyl acetate soluble fraction was condensed at 50 C, and 26.20 g of ethyl acetate...

Ho L H

Figure 1.1 Secure assignments of the ester positions. a day) and the project would never have been pursued. Or if fractionation had been pursued, the cytotoxicity-guided fractionation could have led to the toxic taxines rather than taxol. The related baccatin III was isolated by Chan et al., in 1966, but its structure was not elucidated at that time. A tentative structure, based on chemical and spectrospecific evidence, was published by De Marcano in 1970. Taylor isolated a substance that he...

Simulated Movingbed Chromatography

Simulated moving-bed (SMB) chromatography has been widely used for various industrial applications, for example, sugar and hydrocarbon purification. All industrial-scale SMBs are low-pressure systems and use large adsorbent particles (600-1000 m in diameter). These low-pressure SMBs have proven to be economical for commodity chemicals. SMB chromatography has the same advantages as recycle chromatography, namely, high product purity, high yield, and low desorbent requirements. Wu D.J. et al....

Drying time h

Figure 6.10 Change on extract yield in the needles and bark from T. cuspidata during drying time. * Average percentages of 5 samples based on oven-dried material. ** Control, fresh samples. * Average percentages of 5 samples based on oven-dried material. ** Control, fresh samples. Figure 6.11 Taxol content in the needles and bark from T. cuspidata during drying time. Figure 6.11 Taxol content in the needles and bark from T. cuspidata during drying time. * Percentages based on oven-dried...

Koh

Figure 3-17 C-13 Ketonized group with cinnamoyl group at C-5. Baxter et al. (1962) Dukes et al. (1967) Kurono et al. (1963) Chiang (1975) Chiang et al. (1967) Woods et al. (1968) Liu et al. (1984) Woods et al. (1968) Yeh et al. (1988) Chiang et al. (1967) Baxter et al. (1962) Appendino et al. (1992) Appendino et al. (1992b) Appendino et al. (1992b) Wang et al. (1998) Shrestha et al. (1997) Appendino et al. (1994) Tong et al. (1994) Kosugi et al. (2000) Figure 3-17 C-13 Ketonized group with...

R4o

C 9-Deacetyltaxayuntin E, taxuspinanane F 7,9,10-Trideacetyl-abeo-baccatin VI Taxayunntin E taxayuntin A 4-Deacetyl-11(15 1)-abeo-baccatin VI 4a7 -Diacetoxy-2 a, 9a-dibenzoyloxy- VI (taxachinin I) VI 2a,7 -Dibenzoxy-5 ,20-epoxy-1 Chen and Kingston (1991) Morita et ai. (1998) Appendino et ai. (1994) Yue et ai. (1995a) Chen et ai. (1993) Barboni et ai. (1994a) Guo et ai. (1995a) Chattopadhyay et ai. (1998) Barboni et ai. (1994) Tanaka et ai. (1994) Figure 3.44 Simple taxoids with an oxetane...

Jun Sep Dec 10DAB

Figure 6.3 Seasonal variation of taxoids in the needles of T. cuspidata. Note * Percentages based on oven-dried material. Bars show mean SD. 10-DAB 10-deacetylbaccatin III. The seasonal changes were especially notable for taxol and 10-deacetylbaccatin III content in current leaves, suggesting that these compounds are biosynthesized and accumulated as the trees grow. Correspondingly, we also observed that baccatin III in current needles decreases from June to September. As baccatin III was...

Purification

The extract was then separated using column chromatography (column 4 cm diameter and 50 cm long, packing 300 g of wakogel c-300). The extract was eluted with successive mixtures of hexane and ethyl acetate, 2 1 (v v), 1 1, and 2 3. The residue was eluted with ethyl acetate and then with methanol. Each fraction was examined for taxol using TLC, and the ethyl acetate fraction contained taxol. After evaporation, the residue (2.58g) was dissolved in acetonitrile (2 ml per 100 mg of extract), and...

From both the needle and bark specimens taxol was most efficiently extracted when the specimens were air dried in the

Figure 6.15 Taxol content in the needles and bark from T. cuspidata dried in sun and shade. * Percentages based on oven-dried material. Bars show means SD. ** Control, fresh frozen samples. Figure 6.15 Taxol content in the needles and bark from T. cuspidata dried in sun and shade. * Percentages based on oven-dried material. Bars show means SD. ** Control, fresh frozen samples. the roots of Astragalus mongholicus caused less reduction in component contents than forced drying with hot air (80 C)...

Conclusion and prospective

Generally, because many plant products are accumulated in small amounts in the intact plants and cultured tissues, these products cannot be mass produced efficiently by plantation or tissue culture methods. In order to increase the productivity of taxol and related taxoids by tissue cultures, various strategies, including optimization of culture conditions, selection of high-producing cell lines, the use of elicitors, the addition of precursors, and other approaches have been examined by many...

Structures of novel taxoids Introduction

In the review of Blechert and Guenard (1990), taxoids were classified according to their structure. In 1993, Kingston et al. (1993) edited a review entitled The Taxane Diterpenoids in Progress in the Chemistry of Organic Natural Products. Moreover, the chemistry of taxoids was reviewed in the book Taxol, Science and Applications edited by Suffness in 1995. However, after that many related taxoids have been isolated from natural sources. The first taxoids were isolated because of interest in the...

List of contributors

School of Pharmacy University of Portsmouth Hampshire, UK Department of Pharmacognosy School of Pharmacy University of Dublin Trinity College, Dublin 2, Ireland Department of Pharmacognosy School of Pharmacy University of Dublin Trinity College Dublin 2, Ireland Natural Products Laboratory School of Pharmacy University of North Carolina at Chapel Hill Chapel Hill, NC 27599-7360, USA Gifu Academy of Forest Science and Culture Natural Products Laboratory School of Pharmacy University of North...

Second step of taxol biosynthesis taxadienol formation

No oxygenated taxoids bearing a 4(5)-double bond have been isolated from the plants, whereas taxoids with a 4(20)-ene-5-oxy functional group are common (Kingston et al., 1993). These facts suggest that hydroxylation of taxa-4(5),11(12)-diene at C-5 is associated with migration of the double bond. This step may be next in the taxol biosynthetic sequence (Croteau et al., 1995) (see Figure 2.2). Microsomal preparations from Taxus stem and cultured cells were shown to catalyze the NADPH dependent...

Methods for obtaining materials containing taxoids Quantitative analysis of taxoids in each part of T cuspidata

To establish a method of producing taxol using yew forests, the amounts of taxol, baccatin III, and 10-deacetylbaccatin III in living tissues must be fully understood. We quantitatively analyzed taxol, baccatin III, and 10-deacetylbaccatin III in each tissue of Japanese yew trees (16 years old) growing in an artificial forest in Engaru-cho, Monbetsu-gun, Hokkaido. In addition, we examined the seasonal change in the content of these compounds in the yew tree needles (current and previous years...

Ho

Baccatin III (8) R1 p-OH, R2 Ac 10-Deacetyl-Baccatin III (9) R1 p-OH, R2 H Taxol (1) was first isolated from T. brevifolia (Pacific yew) by the following procedures (Wani et al., 1971). An alcohol extract of the stem bark was concentrated and partitioned between water and chloroform. The residue from the chloroform extract was subjected to bioassay-guided fractionation using three successive chromatographic procedures on Florisil, Sephadex LH-20, and silica gel. The isolated active principle...

The first step of taxol biosynthesis cyclization of GGPP with taxadiene synthase

The first committed step in the biosynthesis of taxol and related taxoids is the cyclization of the universal diterpenoid precursor GGPP to taxadiene (taxa-4(5),11(12)-diene) (Figure 2.1) (Koepp et al., 1995), but not to an exocyclic isomer, taxa-4(20),11(12)-diene, as was proposed earlier based on the abundant occurrence of taxane metabolites with an exo-double bond structure (Gueritte-Voegelein et al, 1987 Floss et al, 1995). In vivo experiments with T. brevifolia stem sections, using labeled...

Phenylalanine amino mutase Walker and Floss 1998

Taxol possess a characteristic benzoylphenylisoserine acyl group. Phenylalanine amino mutase, which is responsible for the formation of p-phenylalanine, was investigated and identified for the first time in cell-free extracts of T. brevifolia. This enzyme has been shown to be a key intermediate in the biosynthesis of taxoid's phenylisoserine side-chain. p-Phenylalanine produced by the cell-free extract was found to have the same configuration as that present in the taxol side-chain. Studies...