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Letter

Total Synthesis and Comparative Analysis of Orlistat, Valilactone, and a Transposed Orlistat Derivative: Inhibitors of Fatty Acid Synthase

Supporting Info

Gil Ma,^† Manuel Zancanella,^† Yatsandra Oyola,^† Robyn D. Richardson,^‡ Jeffrey W. Smith,*^‡ and Daniel Romo*^†;

Department of Chemistry, Texas A&M University, College Station, Texas 77842-3012, and Cell Adhesion and Extra Cellular Matrix Biology, Burnham Institute for Medical Research, Infectious and Inflammatory Disease Center, La Jolla, California 92037

Org. Lett., 2006, 8 (20), pp 4497–4500

DOI: 10.1021/ol061651o

Publication Date (Web): September 2, 2006

†

Texas A&M University.

‡

Burnham Institute for Medical Research.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

, romo@mail.chem.tamu.edu, ; , jsmith@burnham.org

Abstract

Concise syntheses of orlistat (Xenical), a two-carbon transposed orlistat derivative, and valilactone are described that employ the tandem Mukaiyama aldol−lactonization (TMAL) process as a key step. This process allows facile modification of the α-side chain. Versatile strategies for modifying the δ-side chain are described, involving cuprate addition and olefin metathesis. Comparative antagonistic activity of these derivatives toward a recombinant form of the thioesterase domain of fatty acid synthase is reported along with comparative activity-based profiling.

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Published In Issue September 28, 2006
Received July 5, 2006

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Letter

Total Synthesis and Comparative Analysis of Orlistat, Valilactone, and a Transposed Orlistat Derivative: Inhibitors of Fatty Acid Synthase

Abstract

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History

Recommend & Share

Related Content

Enantioselective Synthesis of a Key Intermediate in a New Process for Orlistat Using Asymmetric Hydrogenation and a Grignard Reagent Promoted Lactone Cyclization

A Direct and Efficient Total Synthesis of the Tubulin-Binding Agents Ceratamine A and B; Use of IBX for a Remarkable Heterocycle Dehydrogenation

Asymmetric Synthesis of (−)-Tetrahydrolipstatin: An anti-Aldol-Based Strategy

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