Roche Lecture Series


Wednesday, April 23rd
Professor Minoru Isobe
"Synthesis and Bioorganic Chemistry of Marine Natural Products"

4:15pm - 5:15pm
Braun Lecture Hall
S.G.Mudd Chemistry Building
Stanford University





This special lecture is hosted by Roche Palo Alto Pharmaceuticals in recognition and encouragement of continued excellence within the area of synthetic organic chemistry. The lecture is free and open to the public. All Stanford University Chemistry students are encouraged to attend this special event.

About the lecture:
We have recently concluded two total syntheses of (-)-Tetrodotoxin(1),1 a puffer fish poisoning, and have been studying toward Ciguatoxin (2) as principal toxin of ciguatera poisoning. For the latter, acetylene cobalt complex strategy has been developed with its first and second generation methodology, which includes coupling of the segments, cobalt complexation, cyclization, reductive or oxidative decomplexation for the next ring cyclization. Recently, we have succeded in coupling of the two segments, namely Segment L (3) and Segment R (4), to obtain 5. F-ring was cyclized via the cobalt strategy, and endo-complex (6) was converted to ketone 7. Silane reduction in acidic condition prompted the G-ring cyclization to afford syn/trans stereochemistry, which was modified to the acetylene 8 for the final coupling toward 2. These two natural products (1, 2) interact with sodium channel protein in different ways, and the molecular mechanism are to be elucidated after these compounds and analogs in hands.2 Once we have concluded the total syntheses of these biologically important natural products, we have optional methods by providing molecules requisited for the molecular mechanism studies. Some examples are to be discussed with protein phosphatase and inhibitors, tautomycin diacid and okadaic acid (9, 10),3 as well as some photoprotein and luminous substrates.

I would like to discuss about some other marine natural products related to the molecular mechanism of bioluminescence including small molecular weight chromophore interacting with the photoprotein.



About Isobe:
Minoru Isobe b 1944 in Nagoya, Japan. Nagoya University (B 1967), Nagoya Univ. (M, 1969), Nagoya Univ. (PhD 1973, Prof. T. Goto), Asso. Prof. Nagoya Univ. (1975), Prof. Nagoya Univ. (1991-present ), Postdoc. Columbia Univ. (New York, Prof. G. Stork, 1973-1975). Research field: organic chem., natural product chem., total synthesis with stereochemical control (vernolepin, maytansine, okadaic acid, tautomycin, tetrodotoxin, etc.), synthetic methodology, bioluminescence (mushroom, squid, millipede, earthworm etc.), marine toxins (ciguatoxin, tetrodotoxin), insect hormone (peptide hormone, Time Interval Measurement Protein), Potassium selective ionophore (cereulide, valinomycin). Other appointments, IUPAC Titular Member (2002-), President of Organic and Biomolecular Chemistry Division (2004-07). Editor of Chemistry-An Asian Journal (2006-).

Questions
Please contact Patricia Dwyer at 650-723-4770.