Synthesis of Functionalized Azabicycloalkane Amino Acids as Dipeptide Mimics

Abstract

Functionalized bicyclic lactams serve as building blocks for the synthesis of conformationally constrained peptides. A route to these building blocks is described based on the stereoselective alkylation of an appropriate azabicycloalkane; all possible diaste­reo­isomers can be obtained stereoselectively.

Key words

peptidomimetics - alkylations - lactams - bicyclic compounds - diastereoselective synthesis

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13

X-ray data of isomer 13b were collected on a Bruker Smart Apex CCD area detector using graphite-monochromated Mo-Kα radiation (λ = 0.71073 Å). Data reductions were made using SAINT programs. The structures were solved by SIR-92 and refined on F ² by full-matrix least-squares using SHELXL-97. Crystal data: C₂₇H₃₄N₂O₃, M _r = 434.56, colorless prism 0.34 × 0.16 × 0.13 mm, orthorhombic, P2₁2₁2₁, a = 10.3435 (9), b = 13.0923 (12), c = 17.8267 (15) Å, V = 2414.1 (4) ų, Z = 4, T = 150 (2) K, µ = 0.078 mm^-1; 13026 measured reflections, 4274 independent reflections, 2859 reflections with I>2σ(I), 3.86<2θ <64.26°, R _int = 0.041. Refinement on 4274 reflections, 391 parameters. Final R = 0.0424, wR = 0.0801 for data with F ²>2σ(F ²), (Δ/σ)_max = 0.001, Δρ _max = 0.29, Δρ _min = -0.20 eÅ^-3. Tables of atomic coordinates, anisotropic thermal parameters, bond lengths and angles of isomer 13b may be obtained free of charge from The Director CCDC, 12 Union Road, Cambridge CB2 1 EZ, UK, on quoting the deposition number CCDC 285315, the names of the authors, and the journal citation [fax:[phone]; e-mail: [e-mail]; web site: http://www.ccdc.cam.ac.uk].