Holton, Robert

The first synthesis of Taxol was completed by Robert Holton and co-workers and is outlined in Scheme 13.53. One of the key steps occurs early in the synthesis in sequence A and effects fragmentation of 4 to 5. The intermediate epoxide 4 was prepared from a sesquiterpene alcohol called patchino. 35 The epoxide was then converted to 5 by a BF3-mediated rearrangement. 

Much of the basis of the BMS CRADA proposal was built on the ability of BMS to tap into the tremendous synthetic knowledge contained in Robert Holton s research group at Florida State University (FSU). This research group had been actively studying the chemistry of Taxol and had made significant strides toward a total synthesis and a viable semi-synthetic pathway from 10-DAB. A licensing agreement between BMS and FSU was created, and in 1992 the first commercially viable semi-synthetic route from 10-DAB to Taxol was discovered [13]. 

At the time of the patent suit, it appears that BMS used a semisynthetic process that was licensed from Robert Holton s group at Florida State University. Holton s group not only discovered a highly efficient semisynthesis of paclitaxel from 10-DAB, but also were one of the first two groups (KC Nicolau s group was the other) to complete the total synthesis of paclitaxel, which means they assembled the molecule from commonly available precursors—essentially from scratch. The total synthesis, however, is not and probably never will be a commercially viable way to make this very complex organic molecule. 

William Menke. Geophysical Data Analysis Discrete Inverse Theory. 1989 S. George Philander. El Nino, La niha, and the Southern Oscillation. 1990 Robert A. Brown. Fluid Mechanics of the Atmosphere. 1991 James R. Holton. An Introduction to Dynamic Meterology, Second Edition. 1992... 

A key role played by chemists is learning how to mimic effectively nature s bountiful manufacturing processes. Once in a while, such a strategy—when it pans out—can tell a story of research-to-riches. Robert Holton, an... 

The supply problem was partially solved through improvements in the extraction process from Pacific yew, but a more radical solution was achieved by French groups under the leadership of Pierre Potier in Paris and Andrew Greene in Grenoble. They discovered that the needles of the European yew, Taxus baccata, contained a structural relative of taxol called 10-deacetylbaccatin III to the extent of around 1 g per 3 kg of needles. This natural product could be converted to taxol in four chemical steps in a process discovered by Robert Holton in the USA. Since the European yew grows relatively rapidly, the needles could be harvested and the supply of taxol was thus assured. 

Robert Holton at Florida State University was able to react the baccatin III derivative in a similar way with an enantiomericaUy pure /1-lactam. The overall yield across the comparable stages was around 12 % better. [325]... 

It turned out that yew trees not only of the Pacific coast but of other species contain a compound called 10-deacetylbaccatin III (see Fig. 7.6) this is a precursor of taxol. You see in Fig. 7.6 that taxol consists of two portions A and B, and that this precursor provides the portion A. Now, to make another compound starting with a simpler compound is called Chemical Synthesis, and this is what chemists excel at. Some people even say that this, chemical synthesis, is the only thing that is a proper chemistry. In this case, you have to add portion B on to the existing portion A. Robert A. Holton of Horida State University succeeded in synthesizing taxol from 10-deacetylbaccatin III. 

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