10-Deacetylbaccatin III (10-DAB)
A paclitaxel intermediate isolated from the Yew Tree (Taxus sp.)
10-deacetylbaccatin III (10-DAB) is the fifth intermediate in the biosynthetic pathway of paclitaxel in Taxus species (Walker, 2000).
Initial silica chromatography separates oils and polar components from hyperforin and adhyperforin. Then C18 chromatography is used to separate hyperforin and adhyperforin. Hyperforin is in greater quantity, and in the reversed phase system, hyperforin leads the adhyperforin. This means that the initial fractions will be hyperforin devoid of adhyperforin, and the later fractions will be adhyperforin contaminated with low levels of hyperforin. Both hyperforin and adhyperforin readily form the dicyclohexylamine salt.
Biological Activity:10-deacetylbaccatin III is an intermediate in the biosynthetic pathway of the taxane, paclitaxel. Taxanes disrupt mitosis by preventing microtubule destabilization and spindle fiber formation in animal cells (Molè-Bajer, 1983). As a consequence of this mechanism, yew trees are slow growing organisms. Without mitosis, cells, especially cells with a high replication rate such as tumor cells, cannot divide. Taxanes are currently being investigated as possible treatment for certain cancers, and paclitaxel, is currently approved by the FDA for treatment of AIDS-related Karposi sarcoma, breast cancer, non-small cell lung cancer, and ovarian cancer (National Cancer Institute, 2012).
References:Holton R. (1991) Method for preparation of taxol using an oxazinone. US Patent 5,015,744.
Walker K and Croteau R. (2000) Taxol biosynthesis: molecular cloning of a benzoyl-CoA:taxane 2alpha-O-benzoyltransferase cDNA from taxus and functional expression in Escherichia coli. Proceedings of the National Academy of Sciences of the United States of America. 97(25), 13591-13596.
Elmer W, Mattina M and MacEachern G. (1994) Sensitivity of plant pathogenic fungi to taxane extracts from ornamental yews. Phytopathology. 84(10), 1179-1185.
Molè-Bajer J and Bajer A. (1983) Action of Taxol on Mitosis: Modification of Microtubule Arrangements and Function of the Mitotic Spindle in Haemanthus Endosperm. Journal of Cell Biology. 96, 527-540.
National Cancer Institute. (2012) Cancer Drug Information: Paclitaxel. www.cancer.gov.