An efficient synthetic method for Z-fluoroalkene dipeptide isosteres: Application to the synthesis of the dipeptide isostere of Sta-Ala |
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| Affiliation: | 1. Tokyo Women''s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan;2. Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan;1. Institute of Inorganic Chemistry and Analytical Chemistry, Johannes Gutenberg-University of Mainz, Duesbergweg 10-14, 55128 Mainz, Germany;2. Bundesanstalt für Materialforschung und -prüfung (BAM), Fachbereich 8.6, Optische und faseroptische Verfahren, Unter den Eichen 87, 12205 Berlin, Germany;1. Computational Chemistry Group, Department of Chemistry, University of Mauritius, Réduit, Mauritius;2. The School of Chemistry, The University of Manchester, Manchester M13 9PL, UK;3. Departamento de Química Orgánica, Universidad de Valencia, Dr. Moliner 50, 46100 Burjassot, Valencia, Spain;1. Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306-4390, USA;2. C. Eugene Bennett Department of Chemistry, West Virginia University, Morgantown, WV 26506, USA;1. Department of Chemistry, University of Virginia, Charlottesville, VA 22904, USA;2. Center for Advanced Scientific Computing and Modeling (CASCaM), University of North Texas, Denton, TX 76203, USA |
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| Abstract: | Reaction of γ,γ-difluoro-α,β-enoates having a δ-hydroxyl group with trialkylaluminum (R3Al) was found to be promoted by CuI·2LiCl and to proceed in SN2′ manner giving rise to the α-alkylated (Z)-γ-fluoro-β,γ-enoates, while reductive defluorination of γ,γ-difluoro-α,β-enoates with Me2CuLi followed by reaction with alkyl halides provided the corresponding (Z)-α-alkylated products in high yields. The latter reaction was applied to the preparation of the dipeptide (Z)-fluoroalkene isostere of Sta-Ala, which is the central dipeptide unit in Pepstatin, a natural inhibitor of aspartate proteases. |
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