The Creation of Medicine as Hydrolytic Enzyme Inhibitors

§Background and Purpose§

The industrial technologies of saccharide, that are the basic constituent of organism as nucleic acid and protein, are developing now. Enzyme relevant to carbohydrate has relation with many important phenomenon of virus infection, of recognition among cells , of metastasis of cancer and so on ,and there is no doubt that the Inhibitors against these phenomenon have been expected to go out into the world. Those industrial technologies are the strong candidate of post-genome- industries and they are leading to the elucidation and the control of varied bioactivities, and we expect that those results of industrial technologies contribute to the many areas with a central focus on medical. According to this thought, we have focused on the Inhibitors as the breakthrough of them. Through the molecular design and fine chemical synthesis, we aim to get much potentiality of the Inhibitors to be clear and we aim to develop basic technologies that will be applied future. We have made research and development jointed with the Professor Masanori Yamaura, department of Life Environment of the Faculty of Science and Technology in the Iwaki Meisei University. And this research & development is the result of the business formatting intellectual cluster by Fukushima prefecture from 2002 to 2004.

§Organic chemical approach relating the search of the New Inhibitor§

We focused on 2 or 2,5 – substituted-3-4 – dihydroxypyrrolidine as hydrolytic enzyme inhibitors against carbohydrate, and we,
1. synthesize all stereoisomer as basic structure,
2. experiment systematically using all the stereoisomer.
3. synthesize the various types of all stereoisomer based on the results of the experiments of the Inhibitors.
4. search New Inhibitors with developing the results of these experiments
We planned to make research and development as follows.

§synthesis of chemical substances having basic structure§

2-substituted-3-4-trans- dihydroxypyrrolidines are planned to be synthesized from tartaric acid through optical active cyclic nitrone (Figure 3) , and 2 – substituted-3-4 -cis- dihydroxypyrrolidines are planned to be synthesized from sugar. After that, we established the synthetic method of creating 8 kinds of all stereoisomer of 2-aminomethyl-3,4-dihydroxypyrrolidine (Figure 4), and of creating 4kinds of 2-carboxamido-3-4-trans- dihydroxypyrrolidine (Figure 5).

§The systematic experiments of inhibitors§

Using all stereoisomers of 2-aminomethyl-3-4- dihydroxypyrrolidine and 2-carboxamido-3-4-dihydroxypyrrolidine synthesized by us as started above, we got the systematic experiments of inhibitors against the various types of glucosidases, and researched correlations between comprehensive structure and optical activity. We consider that we try to contact to the various business area, targeting the possibility of medicine