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From Bark to Drugs: How Robert Holden Solved the Mystery of Texor Synthesis?
Recently, as the demand for anti-cancer drugs increases, Paclitaxel, a key ingredient with scarce sources, has received widespread attention. This compound, which comes from the Pacific yew (Taxus brevifolia), not only has important medical value in treating cancer, but its scarcity makes its cost high. In order to meet the market demand, chemists have carried out long and arduous research on total synthesis. Professor Robert Holden is one of the leaders. In 1994, he successfully carried out the total synthesis of texol.
Holden's project began in 1982. His success was not only a breakthrough in scientific research, but also brought revolutionary changes to the pharmaceutical industry.
The chemical structure of Texol consists of a four-ring core - baccatin III (baccatin III) and an amide side chain. These core rings are called A, B, C and D rings respectively. Holden's overall synthesis method is mainly based on the process of Ojima lactone, and is based on bacaldine, and finally adds side chains. This strategy has become a model for many peer researchers to learn from.
As early as 1963, bark extracts from the Pacific yew tree were discovered to have anti-tumor activity, as a result of a U.S. government plant screening program. After years of research, scientists determined the main components of the substance in 1969 and completed structural analysis in 1971. As the scientific community's interest in texol increased, more and more research groups participated in this competition. By 1992, about 30 research groups had participated in it, and finally 11 research groups reported their total synthesis. progress.
This synthesis competition not only stimulated the enthusiasm of the scientific community, but also promoted the rapid development of related technologies.
The commercialization of the results of Holden's team was partly due to the purchase of relevant patents by Bristol-Myers Squibb in 1990. This transaction brought Holden and Florida State University More than $200 million in proceeds. These funds not only support the subsequent development of Holden's research, but also promote the progress of the entire pharmaceutical industry. It is worth mentioning that the earliest semi-synthetic technology of texol was developed by Jean-Noël Denis in 1988, using 10-desacetylbaccatin III as the starting material , to obtain the scale of synthesis.
The synthesis of Texol is full of challenges. Holden's entire synthesis project took more than ten years from start to finish, which was undoubtedly a difficult adventure in the chemical world at that time. With the deepening of research, the synthesis route of texol is also constantly innovating. Many researchers use different precursor molecules and synthesis strategies to try to decipher this complex synthesis mechanism. Various synthesis methods, such as linear synthesis and convergent synthesis, have been proposed one after another, making the synthesis steps of texol increasingly perfect.
This history is not only about the process of chemical synthesis, but also a journey of exploring the unknown of science.
In recent years, researchers have also conducted in-depth studies on the biosynthesis of texol and found that it involves a complex synthesis pathway of approximately 20 enzymatic steps. These studies reveal how nature finely controls stereochemistry and make synthetic synthesis difficult. Nonetheless, according to reports in 2011, E. coli using genetic engineering technology has realized the possibility of producing texel precursors at the kilogram level, opening up new avenues for future synthesis.
In commercial semi-synthesis, many companies such as Natural Pharmaceuticals have also started work, mainly based on transformation of derivatives extracted from original plants to obtain compounds with greater potential. Such research will not only broaden the market for related anti-cancer drugs, but may also promote the discovery and application of new drugs.
With the advancement of technology, the synthesis method of texol will continue to evolve, and the future possibilities are exciting.
In this struggle for chemical synthesis, from Holden's success to future continued research, we can see the power of science and mankind's desire to constantly explore the unknown. In the face of cancer, a challenge to human health, the efforts of the chemical community are not only to produce drugs, but also to bring the understanding and expectations of life into practice. Against this background, we can’t help but wonder: What changes will future anti-cancer drugs bring?
