Twenty-five years ago, I received the Sumiki-Umezawa Memorial Award. As an award winner’s paper, I wrote a review article entitled “Bioprobes for Investigating Mammalian Cell Cycle Control” which was published in The Journal of Antibiotics in 1998. This time, I write a Japanese review article reporting the recent achievements of the Osada group and our collaborators.

We established the Natural Products Depository (NPDepo) in RIKEN and collected many natural compounds. In order to utilize these valuable compounds effectively, we developed a new screening method, the chemical array method. The idea of the chemical array is based on the concept of the DNA microarray, namely the chemical array keeps small molecular compounds instead of DNA on a glass slide. We found that the chemical array is useful in detecting the interaction of proteins with small molecules.

In this review article, the development of the chemical array method and screening results are described.

New molecules, new methods, and new concepts, these were my longstanding goals. For me who has been criticized or advised that the scope of research is too broad, by having the axis of biologically active small molecules produced by microorganisms, I was able to find a focused research area. This paper will focus on my researches after receiving the Sumiki-Umezawa Memorial Award, and I describe my own way of thinking about biologically active small molecules.

Iminosugars, carbohydrate analogues that have a nitrogen atom in place of the carbohydrate ring oxygen atom, have attracted increasing interest as new glycomimetics. Gem-diamine 1-N-iminosugars, proposed by us as a new class of iminosugars, have a nitrogen atom in place of the anomeric carbon. Various kinds of 1-N-iminosugars have been synthesized from glyconolactones as a chiral source by the versatile synthetic strategy in a stereospecific fashion and/or by the convergent strategy from siastatin B, a secondary metabolite of Streptomyces. The protonated form of the 1-N-iminosugar mimics the charge at the anomeric position in the transition state of enzymatic glycosidic hydrolysis, resulting in the strong and specific inhibition for glycosidases and glycosyltransferases. They have recently been recognized as a new source of therapeutic drug candidate in a wide range of diseases associated with the carbohydrate metabolism of glycoconjugates such as tumor metastasis, influenza virus infection, inflammatory disease and so forth. This review describes our research progress in synthesis, biological and pharmacological activity, and the therapeutic potentials of gem-diamine 1-N-iminosugar (gem-diamine 1-azasugar).