Introduction of Research by Division of Organic and Biocatalytic Chemistry, Faculty of Pharmacy, Keio University
Professor Takeshi Sugai


The Division of Organic and Biocatalytic Chemistry in the Faculty of Pharmacy at Keio University, aims to create drugs that will save and improve our life. Through developing our students' knowledge and skill in organic synthesis and biotechnology, our group nurtures competent persons who will globally contribute in various fields.

"Although people in the past did not understand why, food would spoil, or ferment, or bread would rise. These were all the result of living creatures too small for the naked eye, better known as microorganisms. Microorganisms can cause disease, but they can also be useful in making bread, or alcohol, or in other beneficial applications.This falls into an area known as applied microbiology. A microorganism can potentially encounter a completely unknown organic compound of foreign origin and change that compound into something useful. This is the focus of our research."

At the Division of Organic and Biocatalytic Chemistry, students first study the properties of organic compounds that are commonly used as drugs, and then they learn the techniques to synthesize them. Let us suppose we have discovered a drug candidate. Of course that drug will need to be analyzed, but this must be followed by research to adjust the pharmacokinetics, pharmacodynamics, and metabolism to make it into a practical drug. This is the process known as innovative drug development. During this process, various analogs of the lead compounds should be synthesized. At this stage, knowledge and prowess in organic chemistry synthesis are required. As an example, let us show the synthesis of madindoline A.

"Madindolines were discovered by Professor Omura in Kitasato University. They found promising drug candidates for the treatment of osteoporosis. Although these compounds were initially isolated from actinomycete, it later mutated and stopped producing madindolines. This means that we have to supply madindolines by chemical synthesis. Many researchers have undertaken the syntheses of madindolines and our group has accomplished a unique synthesis with a combination of microbiology with organic synthesis. This is the structure of madindoline A. At the lower left is a pentagon and in the upper right you can see a benzene ring, and two other pentagons. If the upper part of the structure is removed, we get this compound on the right which is known to be a key intermediate. This was synthesized using chemical and microbiological methods. We first focused on the construction of the asymmetric center (or chiral center) which has methyl group and the side chain.
Please look at the following scheme. We began with a compound that has this pentagon and a side chain. This compound is easily obtained. When a cultured cells called Torulaspora delbrueckii, a kind of yeast, was applied to this compound, a very interesting reaction occurred. This compound contains three carbonyl groups, but only the one was reduced, and as shown on the right, the product was the cyclic compound. The 99%ee shows that this is an almost completely pure stereoisomer. To go from this compound to the next step, we discovered a reaction via a new radical intermediate. In this reaction, one part of the starting material as a protective group was easily converted into the desired vinyl group. "

Until the 20th century, chemistry was primarily based on petrochemistry. People have generated energy from petroleum-based compounds and used the energy to transform various compounds. But with this method, everything will eventually be depleted. On the other hand, our laboratory utilizes enzymes as catalysts, which are made from proteins. Although proteins themselves cannot be recycled, just one microorganism can easily be proliferated into an infinite number even when fed with the waste products, and produces enzyme proteins.

"In this way, microbiological catalysts are reusable and will undoubtedly become an important source of energy and resources as biocatalysts. However, they should not be used solely in fermentation. Our goal is to exploit them effectively in the design of organic synthesis."

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