Download PDF
Synfacts 2009(7): 0700-0700  
DOI: 10.1055/s-0029-1217252
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of Zaragozic Acid C

Contributor(s):Philip Kocienski, Zofia Komsta
D. A. Nicewicz, A. D. Satterfield, D. C. Schmitt, J. S. Johnson*
University of North Carolina at Chapel Hill, USA
Self-Consistent Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C via Controlled Oligomerization
J. Am. Chem. Soc.  2008,  130:  17281-17283  
CrossrefPubMed
Further Information

Publication History

Publication Date:
22 June 2009 (online)

 PDF Download Permissions and Reprints

Key words

zaragozic acid C - aldol reaction - oxidative kinetic resolution

Significance

The zaragozic acids are picomolar inhibitors of squalene synthase, an enzyme that catalyzes the first step in cholesterol biosynthesis. They also enhance radiochemotheraphy of acute myeloid leukemia cell lines. This formal synthesis features the use of silyl glyoxylate A as a geminal dipolar glyoxylate synthon in the diastereoselective synthesis of C.

Comment

The yield of the oxidative kinetic resolution of racemic C reached 48%. Diastereoselective aldol reaction in E afforded lactone G in good yield and selectivity. Opening of the lactone I with t-BuOK resulted in inversion of the C6 stereocenter. Intermediate L is an intermediate in Carreira’s synthesis of zaragozic acid (J. Am. Chem. Soc. 1995, 117, 8106).

   Permissions and Reprints