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The synthesis and chemistry of the novel reagents and stereochemically defined taxane A-ring building blocks 7e–9e are described, providing the basis for the solution to problems previously encountered in the development of syntheses of taxol and its analogs based on pinene.
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Taxol is a recent and striking example of the continuing impact of natural products chemistry on science and human health and a reminder of the significant return that is realized through investment in basic research. First isolated in the sixties from the bark of the Pacific Yew by chemists Wall, Wani, and their colleagues working in collaboration with the National Cancer Institute (1), taxol was found to possess a novel polycyclic structure (1) punctuated by a central eight-membered ring. Interest in the chemotherapeutic potential of this compound was stimulated by early cytotoxicity studies and greatly amplified by the subsequent proposal by Horwitz and coworkers that taxol operates through a new molecular mode of action involving the facilitated assembly and stabilization of microtubules (2). Clinical trials of taxol in the eighties proved to be sufficiently promising to warrant its subsequent approval for use in the treatment of ovarian cancer and, more