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Multicomponent synthesis of dihydrobenzoxazepinones, bearing four diversity points, as potential α-helix mimics

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Abstract

A very short convergent synthesis of dihydrobenzoxazepinones, bearing four diverse diversity points, based on coupling the Ugi reaction with a Mitsunobu cyclization, was developed. These compounds are potential α-helix mimics, where three of the four appendages are expected to imitate the residues in i, i + 4 and i + 7 positions. A library of 22 compounds bearing lipophilic substituents, designed to interact with the hydrophobic cleft of anti-apoptotic protein Bcl-xL, was synthesized. Preliminary biochemical tests, based on competitive binding, have already been carried out.

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Authors and Affiliations

  1. Department of Chemistry and Industrial Chemistry, University of Genova, via Dodecaneso 31, 16146, Genova, Italy

    Luca Banfi, Andrea Basso, Valentina Cerulli, Giuseppe Guanti, Paulina Lecinska & Renata Riva

  2. Department of Oncology, Biology and Genetics, University of Genova, Largo Rosanna Benzi, 10, 16132, Genova, Italy

    Ilaria Monfardini

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  1. Luca Banfi
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  2. Andrea Basso
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  3. Valentina Cerulli
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  7. Renata Riva
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Correspondence to Luca Banfi.

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Banfi, L., Basso, A., Cerulli, V. et al. Multicomponent synthesis of dihydrobenzoxazepinones, bearing four diversity points, as potential α-helix mimics. Mol Divers 14, 425–442 (2010). https://doi.org/10.1007/s11030-009-9210-4

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  • DOI: https://doi.org/10.1007/s11030-009-9210-4

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