He may be a modest chemist who stays away from the spotlight, but Prof. Marek Cyprian Chmielewski, aged 65, has played a key role in the development of many scientific disciplines that have made our
civilization.

Chmielewski's main field is organic chemistry, or, more precisely, organic synthesis, whose development is prerequisite to progress in many areas of science.

Chmielewski took an interest in chemistry when he was a student at the Bolesław Limanowski High School in Warsaw-thanks to his chemistry teacher Marian Salwin. He developed his interests while studying at the Chemistry Department of the Warsaw University of Technology. After graduation, he stayed on at the university to work as an assistant lecturer at the Faculty of Organic Chemistry. In 1969, Chmielewski moved to the Institute of Organic Chemistry of the Polish Academy of Sciences (PAN), commencing doctoral studies, which he successfully completed by defending his dissertation in November 1971 under the supervision of Prof. Aleksander Zamojski.

While at PAN, Chmielewski was a member of a team that developed a general method for monosaccharide synthesis using simple organic compounds. Complete sugar synthesis cannot replace the production of glucose from starch. Its value lies in developing new methods and new strategies of organic synthesis that later find their application in the pharmaceutical industry. Prof. Zamojski's complete sugar synthesis method was seen as one of the greatest achievements of Polish organic chemistry of the 1970s.

Chmielewski subsequently took part in an internship program in the United States, at the Department of Biochemistry of Purdue University, under the guidance of Prof. Roy Whistler. There, he worked on thiosugars in which the ring oxygen atom was replaced with a sulfur atom-in the case of glucose or fructose, for example. It was expected that such sugars would act as inhibitors in many processes taking place in living organisms. Structurally similar to natural products, they could block active enzyme centers, thus demonstrating antiviral, antidiabetic and antineoplastic properties. This only proved true in the case of the sulfur analogue for glucose, which inhibits glucose metabolism, but which has, as yet, not found any practical application.

After returning to Poland, Chmielewski continued his work on the full synthesis of carbohydrates. The subject of his independent research was the synthesis of deoxy and aminodeoxy sugars that are the ingredients of many modern antibiotics. "It is very satisfying to know that various laboratories took an interest in some of the ideas that I explored in my postdoctoral dissertation; these ideas have found application in the synthesis of the sugar components of anthracycline antibiotics," he says.

After submitting his postdoctoral dissertation, Chmielewski again left for the United States to work at the University of Southern Illinois in Carbondale. He was a member of Prof. James BeMiller's team for 15 months and worked on the synthesis of glycosyltransferase inhibitors.

In 1983, Chmielewski became preoccupied with the synthesis of natural compounds using inexpensive and easily accessible simple sugars such as glucose, galactose and arabinose. This field soon became popular because sugars are renewable resources, meaning that each year nature produces millions of tons of glucose, fructose and other carbohydrates that can be used as raw materials in the pharmaceutical and cosmetic industries. They can also be used for crop protection and in the manufacture of ethyl alcohol.

Chmielewski chose penicillin and cephalosporin oxygen analogues as his objects for synthesis, replacing the sulfur atom of the antibiotic with an oxygen atom. Such oxygen analogues are usually more active than natural compounds, but they are less stable. For this reason only a few have found application in medical therapy so far. Antibiotics from this group are especially popular in the Far East. In Poland, clavulanic acid is a component of a frequently used penicillin-amoxicillin. "Our objective was never the search for new medications," Chmielewski says. "What my team and I were interested in was a synthesis strategy for such compounds, or actually their basic skeleton-that is the coupling of the four-member beta-lactamase ring with five- or even six-member ones. We have demonstrated that the cycloaddition reaction of chlorosulfonyl isocyanate and sugar vinyl ethers leads to attracting input materials for the synthesis of oxygen analogue beta-lactam antibiotics. Obviously, the compounds we developed were tested for antibacterial activity and also as beta-lactamase inhibitors, the enzymes that break down the antibiotic. This was done at the National Institute of Hygiene (PZH). With only one exception, we failed to find the high activity we were interested in."

In the early 1990s, Chmielewski and his team focused on iminosugars as well as aminodeoxysugars. Iminosugars are sugars whose ring oxygen atom is replaced by a nitrogen atom. They demonstrate strong and specific activity as glycoside inhibitors. Glycosides are the enzymes responsible for breaking down saccharide and natural glycoside chains. They have many interesting therapeutic properties, which explains why glycoside inhibitors and glycosyltransferases are currently an important subject of research.

Recent years have seen Chmielewski working on completely new types of sugars as well as glycoside hydroperoxide and peroxide. He has also been preoccupied with the application of these compounds in a process called enantioselective olefin epoxidation. The creation of epoxides is one of the most significant methods for introducing important functional groups into organic compounds. Chmielewski is a pioneer in this field.

Chmielewski has discussed the results of his team's work during lectures at many major scientific events as well as at almost 100 scientific centers in Europe, North America and Asia. He was a visiting professor at the Whistler Center for Carbohydrate Research of Purdue University in 1988 and 1990, as well as at the University of Seville in 1992, and the University of Orléans in 2004.

In spite of the absorbing nature of his research, Chmielewski also finds time for administrative work. Starting with 1987 he was the deputy director of the Institute of Organic Chemistry of the Polish Academy of Sciences, becoming its director in 2004. In 1994-2006, he concurrently worked as deputy chairman of the Polish Academy of Sciences' Division for Mathematical, Physical, and Chemical Sciences, known as Division III.

He became a professor in 1991, and was selected a corresponding member of the Polish Academy of Sciences in 2002.

Under Chmielewski's management, the PAN Institute of Organic Chemistry, in three consecutive league tables, was ranked second, then third, and most recently first among chemical research centers nationwide. "Our institute's doctoral studies center is our pride and joy," Chmielewski says. "We have produced almost 300 doctors. We differ from other similar centers in our consistently implemented educational program. The institute is involved in wide-ranging collaboration with the pharmaceutical industry, both domestic and foreign."

Asked about his greatest scientific achievements, Chmielewski says he has supervised 15 doctorates to date-in between his own scientific projects and publications.

Danuta Górecka