A proof of no anomerization in gas phase.

1. Kanie, O. et al. Proc. Jpn Acad. Ser. B, 2009, 85, 204-215.
   

    Carbohydrates isomerizes in water. This is called anomerization. The ring of an hemiacetal opens to form an aldehyde in the presence of water and closes again forming a cyclic hemiacetal again. During the process, configuration of hydroxyl group at the anomeric position epimerize. This phenomenon was discovered by Dubrunfaut in 1846 about 50 year before Fisher received the Nobel prize.

    In the 19th century, sugar was one of the major merchandise that of course lead to profit. How SWEET! The sugar chemistry was active in connection to the economical situation. The polarimeter was used for the quality control purpose leading to the discovery of mutarotation caused by the anomerization process.

    We are investigating the detail chemical events taking place during the collision-induced dissociation (CID) reactions inside the mass spectrometer. We took a sodiated hemiacetal species and analyzed the behavior of the ion by the energy-resolved mass spectrometry in the stage-discriminated manner. We found that the sodiated hemiacetals do not anomerize in gas phase. This is fundamentally important as the basis of methods based on CID, because the type of ion species retain the anomeric configuration originated in their precursors thus one can get information about the configuration of a particular glycosidic linkage of oligosaccharide.

   Based on this finding, we showed that 1) mutarotation process can be monitored by mass spectrometry and 2) possibility in investigating a mechanism of glycosidase reactions (stereo-inversion vs. retention).

1. Daikoku, S. et al. Carbohydr. Res. 2009, 344, 384-394.
   

We developed a novel method named as Stage-Discriminated Correlation) to reveal whether an totally unknown oligosaccharide (not limited to though) sample is “pure” or not. The basis of this is the individual chemical entities carry a characteristic activation energies, which can be observed by the energy-resolved mass spectrometry technique.

Stereospecific synthesis of hemiacetals in gas phase

Stereospecific generation of individual anomers of hemiacetals in gas phase: A first acomplishment

　Aminobutyl alpha- and beta-glycosides of lactose were individually subjected to collision-induced dissociation conditions to produce hemiacetal and pyrollidine. The generated hemiacetal was found to have the stereochemistry retained.

1. Suzuki, K. et al. Anal. Chem., 2007, 79, 9022-9029.
   

2. Shioiri, Y. et al. J. Mass Spectrom., 2008, 43, 1132-1139.
   

Blockbuster Paper

Papers with sum of number of citations during continuing five years exceeding 50 is called blockbuster paper.

1. Carbohydrate Research, 1993, 243, 139-164.
   

2. 　　8 times (1999-2006)
   

3. Journal of the American Chemical Society, 1994, 116, 12073-12074.
   

4. 　　10 times (2000-2009)
   

5. Angewandte Chemie International Edition, 1996, 35, 2510-2512.
   

6. 　　4 times (2002-2005)
   

7. Angewandte Chemie International Edition, 1998, 37, 1524-1528.
   

8. 　　3 times (2005-2007)
   

These papers have very long life that pleases me, but it takes at least six years to be evaluated. This is critical in the current evaluation system. People will be fired before it is acknowledged by others. We might try strategically publish short-live high impact papers as well. Well, what a hell. I matters but I do not care.

Chemoinformatics:

a missing view point

Structural information contained in a combinatorial library:

Combinatorial chemistry has been a focus area in connection with drug discovery in pharmaceutical companies. The definition of the term is the method of creating a series of compounds using multiple components, of which numbers greater than two, in a way of combination. A set of compounds created in this manner is called a combinatorial library. The term combinatorial chemistry is often used together with a following high-throughput screening, thus it is thought to speed-up a process of finding seed compounds through generation of diverse compounds and the screening.

Despite the advantage of the method, it is ignored that the structural information contained in the generated diverse compounds. Such information will be extremely useful in structural analysis, structure-activity relationship, etc. These are buried and the compounds found out to be non-active is dumped. In this manner, structurer-activity relationship is discussed only for the hit compounds where the definition of hit is generally biased. Chemoinformatics thus has a fundamental problem.

One may say “Well, what is wrong? This is the definition.” This is true, but it is also true that a value of structural information in the diversity is missed. We can find such value in synthesized compounds. The problem probably associates with the situation that the current science is so dependent on commercialism and so we do not get enough time for the research. Commercialism may be tolerated but the issue is the time. Is our efforts for tomorrow, day after tomorrow, or ... It seems we are allowed to do things for tomorrow only. This is the problem.