Open AccessSynthesis of C11-Desmethoxy Soraphen A1α: A Natural Product Analogue That Inhibits Acetyl-CoA Carboxylase
Author(s) -
Daniel P. Canterbury,
Keith G. Scott,
Ozora Kubo,
Rolf Jansen,
John L. Cleveland,
Glenn C. Micalizio
Publication year - 2013
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml400377p
Subject(s) - natural product , acetyl coa carboxylase , total synthesis , pyruvate carboxylase , heteroatom , product (mathematics) , chemistry , computer science , combinatorial chemistry , computational biology , stereochemistry , biochemistry , enzyme , biology , ring (chemistry) , organic chemistry , mathematics , geometry
A synthesis of C11-desmethoxy soraphen A 1α is described that proceeds in just 14 steps from readily available starting materials. This natural product analog was identified as a target of interest in a program aimed at identifying novel natural product-inspired inhibitors of acetyl-CoA carboxylase (ACC) as potential anticancer therapeutics. While describing the most efficient synthesis of a soraphen A 1α analog (total syntheses of the natural product have been reported that proceed in 25 to ≥40 linear steps), we also present data supporting the conclusion that C11-heteroatom functionality is a beneficial but unnecessary structural characteristic of soraphen A 1α analogs for inhibiting ACC.