Indole-isonitrile in the Ugi reaction: Application to the synthesis of Omuralide and Salinosporamide A

ORGN 739

Cynthia Gilley, Matthew J. Buller, mbuller@chem.ucsd.edu, and Yoshihisa Kobayashi, ykoba@chem.ucsd.edu. Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Dr, Mail Code 0343, La Jolla, CA 92093-0343
Our ongoing efforts into the total synthesis of the potent proteasome inhibitors, Omuralide and Salinosporamide A, required the development of a new “convertible” isonitrile for use in the Ugi four-component condensation reaction. Indole-Isonitrile 1 was employed in the key step of our synthetic approach to Omuralide. The Ugi reaction of γ-ketoacid 2 yielded the bicyclic lactam 3 in 70% yield as a single diastereomer. The utility of 1 stems from its facile hydrolysis to a carboxylic acid or ester functionality. 1 can be converted to an N-acylindole with catalytic acid (CSA, PhH), which is easily hydrolysed to a carboxylic acid with weak base (Cs2CO3, DMF/H2O). Further progress towards the syntheses will be reported.

 

Total Synthesis, Materials, Molecular Recognition, Process R&D, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster

Division of Organic Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006