title: Synthesis of C11-Desmethoxy Soraphen A1α: A natural product analog that inhibits acetyl-CoA carboxylase.
abstract: A synthesis of C11-desmethoxy soraphen A1αis 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 A1αanalog (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 A1αanalogs for inhibiting ACC.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Canterbury
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458.
authors.forename: Kristen E N
authors.initials: KE
authors.lastname: Scott
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458.
authors.forename: Ozora
authors.initials: O
authors.lastname: Kubo
authors.affiliation: Helmholtz Centre for Infection Research, Department of Microbial Drugs, Braun-schweig, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Jansen
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458.
authors.forename: John L
authors.initials: JL
authors.lastname: Cleveland
authors.affiliation: Department of Chemistry, The Scripps Research Institute, Jupiter, FL 33458.
authors.forename: Glenn C
authors.initials: GC
authors.lastname: Micalizio
keywords: Soraphen A; acetyl-CoA carboxylase (ACC); function-oriented synthesis; polyketide synthesis