Total synthesis of (-)-(E)-15,16-dihydrominquartynoic acid: A potent anti-cancer natural product

ORGN 415

Benjamin W. Gung, Department of Chemistry and Biochemistry, Miami University, Oxford, OH 45056 and Godwin Kumi, Department of Chemistry and Biochemistry, Miami University, Oxford, 205 Hughes Hall, Oxford, OH 45056.
E-15,16-dihydrominquartynoic acid is one of the three polyacetylenic compounds isolated from a chloroform-soluble extract of the twigs of Onchanostachys amentacea, a tree indigenous to western Malaysia and parts of Indonesia.

In a bioassay-guided phytochemical investigation of this extract E-15,16-dihydrominquartynoic acid was found to have the most potent activity in among the three O. amentacea isolates against the KB, LNCaP (human hormone dependent prostate cancer), and SW626 (human ovarian) cells lines.

We are pleased to report the total synthesis of E-15,16-dihydrominquartynoic acid in seven linear steps and an overall yield of 27.6% from commercially available (S)-methyl lactate. The key step is a one-pot desilylation¨Ccross coupling to construct the entriyne unit.

Unlike the three component Cadiot-Chodkiewicz coupling reaction we used in synthesizing the other two polyacetylenic compounds, where we had two other side products in addition to our desired product, the yield on the one-pot desilylation-cross coupling was much better because there was no side product.

 

Total Synthesis, Asymmetric Reactions and Syntheses, Bioorganic
9:00 AM-11:00 AM, Wednesday, March 31, 2004 Anaheim Convention Center -- Hall C, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, March 29, 2004 Anaheim Convention Center -- Hall A, Sci-Mix

Division of Organic Chemistry

The 227th ACS National Meeting, Anaheim, CA, March 28-April 1, 2004