Taxol analogues

One method of synthesis of taxol analogues starts with a-pinene (8), the readily available and inexpensive monoterpene derived from the processing of turpentine from the pine tree (200). The a-pinene is oxidized to verbenone, which is then alkylated and converted to taxol analogues in a multistep process. 

Another monoterpene used as a starting material for taxol analogues is camphor (43), which is readily available naturally or can be produced synthetically (201,202). Total synthesis of taxol analogues may be the answer toward finding new compounds for the treatment of many types of cancer. 

Partial hydrolysis of an oxazoline to produce the hydroxy amide was used extensively in the synthesis of Taxol analogues (Table 8.24 Scheme It is noteworthy that a solution of the amino... 

The paclitaxel (Taxol) analogue 33 in which the D-ring is modified by sulfur has been oxidized with MCPBA to the S, -dioxide 34 in 61% yield (Equation 8) <1999JOC2694>. 

Kant, J. O Keffe, W. S. Chen, S.-H. Farina, V. Fairchild, C. Johnston, K. Kadow, J. R Long, B. H. Vyas, D. A chemoselective approach to functionalize the C-10 position of 10-deacetylbaccatin III. Synthesis and biological properties of novel C-10 taxol analogues. Tetrehedron Lett., 1994, 35 5543-5546. 

Swindell, C. S. Krauss, N. Horwitz, S. B. Ringel, I. Biologically active taxol analogues with deleted A-ring side chain substitutents and variable C-2 configurations. J. Med. Chem., 1991, 34 1176-1184. 

Chen, S.-H. Kadow, J. F Farina, V. First synthesis of novel paclitaxel (Taxol) analogues modified at the C4-position. J. Org. Chem., 1994, 59 6156-6158. 

Distefano, M. Scamhia, G. Ferhni, C. GaUo, D. De, Vincenzo, R. Filippini, P Riva, A. Bombardelli, E. Mancuso, S. Antitumor activity of paclitaxel (Taxol) analogues on MDR-posititive human cancer cells. Anticancer Drug Des., 1998, 13 489 99. 

Liu C, Strobl JS, Bane S, Schilling JK, McCracken M, Chat-terjee SK, Rahim-Bata R, Kingston DGI. Design, synthesis, and bioactivities of steroid-Unked taxol analogues as potential targeted drugs for prostate and breast cancer. J. Nat. Prod. 2004 67 152-159. 

Theurillat-Moritz, V, Vogel, P, Synthesis of enantiomerically pure 7-oxabicyclo[2.2.1]hept-2-enes precursors in the preparation of taxol analogues. Tetrahedron Asymmetry, 1, 3163-3168, 1996. 

Gueritte-Voegelein, R, Guenard, D., Lavefle, P., Le Goff, M. T, Mangatal, L., Potier, P. Relationships between the structure of taxol analogues and their antimitotic activity. J. Med. Chem. 1991, 34, 992-998. 

Many taxol analogues have been developed and are in various stages of clinical trials, but none has yet been approved for clinical use. Four compounds are however in advanced Phase III clinical trials. TXD258 (27) is a... 

Our search for taxol analogues began with the isolation and identification of taxol and known taxanes. In this way, we could test the efficacy of our analytical selection process and verify the identity of putative taxanes by data comparison to known compounds. Our most effective selection tools are taxol and taxane specific CIEIA, photodiode array detection HPLC, which provides a full ultraviolet spectrum for any point on the chromatographic trace, and mass spectrometry. The general protocol for the isolation and identification of fungal taxol and taxanes is outlined below [1]. 

Kant J, O Keeffe WS, Chen S-H, Farina V, Fairchild C, Johnston K, Kadow JF, Long BH, Vyas D (1994) A Chemoselective Approach to Functionalize the C-10 Position of 10-Deacetylbaccatin III. Synthesis and Biological Properties of Novel C-10 Taxol Analogues. Tetrahedron Lett 35 5543... 

Georg GI, Ali SM, Boge TC, Datta A, Falborg L, Himes RH (1994) Selective C-2 and C-4 Deacylation and Acylation of Taxol The First Synthesis of a C-4 Substituted Taxol Analogue. Tetrahedron Lett 35 8931... 

Synthesis of C-2 Taxol Analogues. Angew Chem Int Ed Engl 33 1581... 

Gueritte-Voegelein F, Guenard D, Lavelle F, Le Goff M-T, Mangatal L, Potier P (1991) Relationships between the Stmcture of Taxol Analogues and Their Antimitotic Activity. J Med Chem 34 992... 

Swindell CS, Krauss NE, Horwitz SB, Ringel I (1991) Biologically Active Taxol Analogues with Deleted A-Ring Side Chain Substituents and Variable C-2 Configurations. J Med Chem 34 1176... 

Georg GI, Boge TC, Cheruvallath ZS, Harriman GCB, Hepperle M, Park H, Himes RH (1994) Topliss Approach to the Synthesis of Biologically Active Substituted N-Benzoyl Taxol Analogues. Bioorg Med Chem Lett 4 1825... 

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