Natural Product Chemistry Laboratory,
Department of Applied Chemistry Faculty of Engineering, Osaka Institute of Technology
Previous research
Total synthesis of 9-membered ring enediyne antibiotics and elucidation of molecular recognition mechanism
2000-2005, Tohoku University (Hirama Laboratory)
We succeeded in first total synthesis of antitumor antibiotic N1999-A2, which has an unstable 9-membered ring-enediyne skeleton, and clarified the absolute stereochemistry of natural product. We also provided the chemical evidence of a thiol-triggered aromatization and showed the unique DNA cleavage profiles of a series of stereoisomers, which proved that the stereochemical orientation of the C11-naphthoate unit played a dominant role in defining efficiency and specificity in the DNA recognition and cleavage process. By applying this synthetic method, we also succeeded in the total synthesis of the aglycone of neocarzinostatin chromophore, a therapeutic agent for hepatocellular carcinoma.
Synthetic study of ciguatoxins, the causative toxins of
ciguatera poisoning
2000-2005, Tohoku University (Hirama Laboratory)
Ciguatoxins (CTXs), the causative toxins of ciguatera seafood poisoning, are huge polycyclic ethers composed of thirteen ether rings ranging from 5- to 9-membered. We succeeded in the syntheses of the ABCDE ring of ciguatoxin and CTX3C. We developed a divergent synthetic strategy using a tetracyclic compound (ABCD ring) as a common intermediate. The syntheses feature a short-step installation of the dihydroxybutenyl substituent into the ABCD ring (for ciguatoxin) and an efficient construction of the E ring using the O,S-acetal forming reaction (for ciguatoxin) or the diastereoselective Aldol reaction (for CTX3C).
Synthetic study of mushroom-derived polycyclic diterpenes
2005-2009, Osaka Prefecture University (Toyota Laboratory, Ryu Laboratory)
Erinacine E is a potent stimulator of nerve growth factor synthesis isolated from Lion's mane mushroom. We succeeded in the stereoselective synthesis of the CDE ring moiety of erinacine E by developing a new method to construct a hydroisobenzofuran skeleton using an intramolecular Pummerer type reaction. Further studies aiming for total synthesis is ongoing.
Investigation of new radical reactions
2005-2009, Osaka Prefecture University (Ryu Laboratory)
In the course of our program to develop new radical reactions with CO, tin-free radical/ionic hydroxymethylation reaction was investigated. The reaction proceeded efficiently in the presence of tetrabutylammonium borohydride as a hydrogen source under atmospheric pressure of CO with photoirradiation. We also developed a new radical cyclization method employing hydrazine as a new leaving group.
Stereoselective synthesis of a key synthetic intermediate of
1β-methylcarbapenems
2005-2009, Osaka Prefecture University (Ryu Laboratory)
We achieved an enantioselective synthesis of 3,4,5,6-tetrasubstituted 3,4-dihydropyran-2-ones bearing a nitrogen substituent at C4 by means of organocatalytic cycloadditions. This is the first example using the organocatalytic reaction to construct the four contiguous asymmetric centers of 1β-methylcarbapenem skeletons.
