Knowles, Nobel prize

Monsanto s commercial route to the Parkinson s drug, L-DOPA (3,4-dihydroxyphenylalanine), utilizes an Erlenmeyer azlactone prepared from vanillin. The pioneering research in catalytic asymmetric hydrogenation by William Knowles as exemplified by his reduction of 24 to 25 in 95% ee with the DiPAMP diphosphine ligand was recognized with a Nobel Prize in Chemistry in 2001. ... 

William S. Knowles (1917-) was born in Taunton, Massachusetts, and received his Ph.D. from Columbia University in 1942. Following his graduate studies, he began work at the Monsanto Company in St. Louis, Missouri, where he remained until his retirement in 1986. He received the 2001 Nobel Prize in chemistry for his work on enantiosefective synthesis, one of the few non-academic scientists to be thus honored. 

William Knowles at the Monsanto Company discovered some years ago that u-amino acids can be prepared enantioselectively by hydrogenation of a Z enam-ido acid with a chiral hydrogenation catalyst. (S)-Phenylalanine, for instance, is prepared in 98.7% purity contaminated by only 1.3% of the (H) enantiomer when a chiral rhodium catalyst is used. For this discovery, Knowles shared the 2001 Nobel Prize in chemistry. 

A different approach to making chiral drugs is asymmetric synthesis. An optically inactive precursor is converted to the drug by a reaction that uses a special catalyst, usually an enzyme (Chapter 11). If all goes well, the product is a single enantiomer with the desired physiological effect In 2001, William S. Knowles, Ryogi Noyori, and K. Barry Sharpless won the Nobel Prize in chemistry for work in this area. 

The standard work of Evans [2] as well as a survey of the papers produced in the Journal of Labeled Compounds and Radiopharmaceuticals over the last 20 years shows that the main tritiation routes are as given in Tab. 13.1. One can immediately see that unlike most 14C-labeling routes they consist of one step and frequently involve a catalyst, which can be either homogeneous or heterogeneous. One should therefore be able to exploit the tremendous developments that have been made in catalysis in recent years to benefit tritiation procedures. Chirally catalyzed hydrogenation reactions (Knowles and Noyori were recently awarded the Nobel prize for chemistry for their work in this area, sharing it with Sharpless for his work on the equivalent oxidation reactions) immediately come to mind. Already optically active compounds such as tritiated 1-alanine, 1-tyrosine, 1-dopa, etc. have been prepared in this way. 

For a related complex, see W. V. Konze, B. L. Scott, and G. J. Kubas, J. Am. Chem. Soc. 124 (2002), 12 550 Bill Knowles shared the 2001 Nobel Prize (with Barry Sharpless and Ryoji Noyori) for his development of catalytic asymmetric hydrogenation. 

The asymmetric hydrogenation of cinnamic acid derivatives has been developed by Knowles at Monsanto [4], The synthesis of L-dopa (Figure 4.3), a drug for the treatment of Parkinson s disease, has been developed and is applied on an industrial scale. Knowles received the Nobel Prize for Chemistry in 2001 together with Noyori (see below, BINAP ) and Sharpless (asymmetric epoxidation). 

I. Noyori, R. Ohta, M. Hsiao, Y. Kitamura, Ma. Ohta, T. Takaya, H. J. Am. Chem. Soc. 1986, 108, 7117. Ryoji Noyori (Japan, 1938—) and Herbert William S. Knowles (USA, 1917—) shared half of the Nobel Prize in Chemistry in 2001 for their work on chirally catalyzed hydrogenation reactions. K. Barry Sharpless (USA, 1941—) shared the other half for his work on chirally catalyzed oxidation reactions. 

One of the success stories of transition metal catalysis is the rhodium-complex-catalyzed hydrogenation reaction. Asymmetric hydrogenation with a rhodium catalyst has been commercialized for the production of L-Dopa, and in 2001 the inventor, Knowles, together with Noyori and Sharpless, was awarded the Nobel Prize in chemistry. After the initial invention, (enantioselective) hydrogenation has been subject to intensive investigations (27). In general, hydrogenation reactions proceed... 

L-Dopa was produced industrially by Hoffrnann-LaRoche, using a modification of the Erlenmeyer synthesis for amino acids. In the 1960s, research at Monsanto focused on increasing the L-Dopa form rather than producing the racemic mixture. A team led by William S. Knowles (1917—) was successful in producing a rhodium-diphosphine catalyst called DiPamp that resulted in a 97.5% yield of L-Dopa when used in the Hoffrnann-LaRoche process. Knowles s work produced the first industrial asymmetric synthesis of a compound. Knowles was awarded the 2001 Nobel Prize in chemistry for his work. Work in the last decade has led to green chemistry synthesis processes of L-Dopa using benzene and catechol. 

In 2001, Knowles and Noyori s pioneering achievements in this field were honored with the award of the Nobel Prize in Chemistry. 

The 2001 Nobel Prize in chemistry was shared by W. S. Knowles, who developed these chiral hydrogenations at Monsanto R. Noyori, who also worked in the area of chiral hydrogenations and K. B. Sharpless, who developed methods for chiral epoxi-dation reactions. 

In the light of the above set of examples, it is obvious why it is so important to produce chirally pure substances [68], Three scientists from among those who worked out reliable and efficient techniques for this purpose were awarded the Nobel Prize for Chemistry in 2001, K. Barry Sharpless, William S. Knowles, and Ryoji Noyori. The Swedish academician who introduced the three scientists at the award ceremony stressed that they have developed chiral catalysts in order to produce only one of the [chiral] forms [69], Chiral production and separation continue to be among the most practical problems in the application of chemical advances [70],... 

In the intervening four years since the appearance of Volume 22, there has both joy and sadness on the advisory board. In a wonderful recognition of the importance of stereochemistry in synthesis and catalysis, the Nobel Foundation Awarded the 2001 Nobel Prize in Chemistry to two of our board members, Ryoji Noyori and K. Barry Sharpless (along with William S. Knowles). Congratulations ... 

Another example of how catalysis plays a key role in enabling our lives is in the synthesis of pharmaceuticals. Knowles s development, at Monsanto in the early 1970s, of the enantioselective hydrogenation of the enamide precursor to L-DOPA (used to treat Parkinson s disease), using a Rh-chiral phosphine catalyst (Section 3.5), led to a share in the Nobel prize. His colaureates, Noyori and Sharpless, have done much to inspire new methods in chiral synthesis based on metal catalysis. Indeed, the dramatic rise in the demand for chiral pharmaceutical products also fuelled an intense interest in alternative methodologies, which led to a new one-pot, enzymatic route to L-DOPA, using a tyrosine phenol lyase, that has been commercialized by Ajinomoto. 

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