Synthesis of geldanamycin, selective formation of the para-quinone

ORGN 297

Erik J. Hicken and Merritt B. Andrus. Dept. of Chemistry and Biochemistry, Brigham Young U, C100 BNSN, Provo, UT 84602
The synthesis of the antitumor ansamycin geldanamycin was previously completed using a demethylative oxidation of a trimethoxyphenyllactam intermediate. This yielded a 10:1 mixture of the un-natural ortho-quinone product together with the para-quinone, geldanamycin. A new approach involving oxidation of the methoxyphenol or the dihydroquinone intermediate has been developed. The best conditions include palladium on carbon with air to give the desired para-quinone in 98% yield. Various oxidants, substrates, and spectroscopic data will be presented that establish the new route.

 

New Reactions and Methodology
8:00 AM-12:00 PM, Tuesday, September 9, 2003 Sheraton New York -- Royal Ballroom B, Oral

Division of Organic Chemistry
The 226th ACS National Meeting, New York, NY, September 7-11, 2003