Molecular and Chemical Life Science :
Chemical Biology


Biostructural Chemistry

Biostructural Chemistry

Marine natural products have great potential for use as pharmaceutical agents, agrochemicals, and chemical probes for biological studies. Our research projects have focused on the total synthesis of complex marine natural products with potent biological activity. We are pursuing research projects in chemical biology, including the design and synthesis of artificial analogues of natural products to improve their biological activity, and to provide understanding of the mechanism of action for the naturally occurring molecules.

Natural products, secondary metabolites produced by organisms, have long been an important source of agrochemicals and potential therapeutic drugs for human diseases, and are well-known chemical probes for cell biology and physiology. More recently, due to their novel structure and potent biological activity, natural products of marine origin have interested many researchers in the life sciences, including synthetic chemists, biochemists, and pharmacologists. However, the inherent molecular complexity and low natural abundance of many of these compounds have precluded their supply for extensive biological studies. Therefore, total synthesis of these compounds is required to provide a sustainable supply to further investigate and exploit their biological functions. Our research group focuses on the total synthesis of structurally complex marine natural products that have potent biological activity for their stereochemical analysis and extensive biological studies. Our efforts are also directed towards the design and synthesis of structurally simplified analogues that retain the original biological functions and might otherwise be inaccessible. These studies will enable the preparation of novel bio-functional molecules for ultimate use in the investigation of broader questions in biology or medicine.

Research Overview

To date, we have developed a method for the convergent synthesis of natural polycyclic ether products by means of the Suzuki-Miyaura reaction, and have achieved the first total syntheses of gambierol, gymnocin-A, brevenal, and gambieric acid A. Significantly, we were the first laboratory to elucidate that gambierol is a specific inhibitor of voltage-gated potassium ion channels (Kv channels). It is of note that there have been only a few examples of the identification of target proteins for natural polycyclic ether marine products. In addition, on the basis of our structure-activity relationship studies, we successfully designed a structurally simplified analogue of gambierol, which exhibits inhibitory activity against Kv channels in a similar manner to the natural product. Our other achievements include: (1) A concise synthesis and detailed structure-activity relationship profile of neopeltolide; (2) total synthesis, structure-activity relationships, and modes of action of exiguolide; (3) total synthesis of polycavernoside-A using the Suzuki–Miyaura reaction; (4) total synthesis and stereochemical reassignment of didemnaketal B, an HIV-1 protease inhibitor; and (5) efficient synthesis of dysiherbaine, a selective kainate receptor agonist, and its synthetic analogs, to elucidate the binding modes at the atomic level.

Faculty Members

Professor SASAKI Makoto
  • Total synthesis of structurally complex marine natural products with significant biological activities
  • design and synthesis of structurally simplified analogues that retain the biological activities
Assistant Professor UMEHARA Atsushi
Natural Product Synthesis, Synthetic Organic Chemistry