Successful Total Synthesis of a Naturally Occurring Immunosuppressive Substance

We have succeeded in the total synthesis of palau’amine, an immunosuppressive substance that was isolated from the extract of a sponge that grows in Micronesia.・Although many chemists had found it difficult to construct the complicated structure, we succeeded in the first chemical synthesis in Japan (the second in the world).

This result would lead to new development of immunosuppressants that are indispensable for the survival of patients who have received organ transplants.
Overview
Palau’amine is a natural organic compound that was isolated from the extract of a sponge that grows near the shores of the western Caroline Islands in Micronesia. This compound has attracted the world’s interest because it exhibits strong immunosuppressive activity that is comparable to that of the immunosuppressant cyclosporine that is widely used to prevent rejection in organ transplant patients. The chemical synthesis of palau’amine and its analogs is necessary for elucidating the mechanisms of immunosuppressive activity, and it has importance for society with regard to the development of new pharmaceutical products.Because of its tremendously complex molecular structure consisting of one carbocycle and five nitrogen-containing rings, palau’amine has been considered one of the most difficult organic compounds to synthesize. Professor Keiji Tanino of Hokkaido University, in joint research with Professor Kosuke Namba of Tokushima University, succeeded for the first time in Japan (second in the world) in the chemical synthesis of palau’amine, and verified that the synthetic product shows strong immunosuppressive activity.

This research was published in the electronic edition of Nature Communications, a British science magazine, on November 4.
Background
Recently, many organic compounds that are candidates for new pharmaceutical products have been discovered from various marine organisms. For example, eribulin, which was recently approved as an anti-cancer agent for breast cancer, is a pharmaceutical product that was developed from the chemical structure of the organic compound called halichondrin B, which was isolated from the extract of Halichondria okadai, a type of sponge. In this way, sponges have attracted attention as the rich repository of candidate compounds for pharmaceutical products, and exploratory research has been performed throughout the world. In 1993, the natural organic compound palau’amine was isolated from the extract of the sponge Stylotella agminata, which grows near the shore of the western Caroline Islands of Micronesia in the western Pacific Ocean. Palau’amine shows extremely strong immunosuppressive activity, and it has been identified that the strength of its activity is comparable to that of the immunosuppressant cyclosporine that is widely used to prevent rejection in organ transplant patients. For this reason, many synthetic organic chemists have attempted the chemical synthesis of palau’amine. However, since it has a tremendously complex molecular structure, consisting of six rings involving one carbocycle and five nitrogen-containing rings, it had been considered to be one of the most difficult organic compounds to synthesize until the first synthesis by a US group in 2010.

Source: University of Hokkaido