|The main research theme of this lab. is organic synthesis (total synthesis) of biological ly active natural products possessing novel chemical structure as well as potent and/or unique biological activities. Development of organic reaction for the synthesis and elucidation of mechanism of the biological activity is also studied.
(1) Total synthesis of bioactive natural products possessing many functional groups.
We are studying total synthesis of natural products possesing unprecedented chemical structures and/or unique biological activities. As the target natural products is small (molecular weight up to 500) but densely functionalized, the synthesis is quite challenging. Therefore development of new synthetic methodologies is necceasry. Elucidation of molecular mechanisms of the biological activity and design and synthesis of of new molecules based on the natural products will studied.
|(2) Synthesis of tetrodotoxin and its analogues, and elucidation of biological issues associated with tetrodotoxin.
Tetrodotoxin (TTX), a puffer fish toxin, exhibits potent and highly selective inhibition of Na ion influx through voltage-dependent sodium channels. In 2003, the first asymmetric total synthesis was reported, and in 2004, an alternative and efficient total synthesis was reported from this lab. Recently, 5-deoxyTTX and 5,6,11-trideoxyTTX were synthesized (unpublished results). We still continue the synthetic studies of TTX and its analogues in order to supply isotope-labeled derivatives and to develop subtype selective blocker of Na-channels based on TTX.
|(3)Synthesis of C-mannosyl-tryptophan and its bioorganic chemistry studies.
C-mannosyl tryptophan (C-Man-Trp) was first found from RNase2 of human urine, and later from many biologically important proteins. On the other hand, the C-Man-Trp was also found,as an amino acid from urine and blood, development of biomarker for renal function is currently investigation. However, the biological role and enzyme involving the biosynthesis has notbeen clarified yet. Since supply of the molecule form natural sources is quite difficult, we are synthesizing C-Man-Trp to supply the C-Man-Trp and its analogues for elucidation of the biological issues.
(4) Development of novel organic reaction and synthetic methodologies for the total synthesis.
Since synthesis of the above-mentioned natural products is quite difficult by simple combination of known reactions, we have been developing new synthetic methodologies and a variety of reactions for the synthesis for the total synthesis of natural products. In the course of the synthetic studies of natural products, we sometimes encounter unexpected reactions, which may inspire new reactions.
(a) Stereocontroled synthesis of multi-functionalized cyclobutane
(b) Reverse prenylation of indole derivatives with cobalt-acetylene complex
(c) Multi-functionality of N-trichloroacetamide