Straightforward Synthesis of a Novel Class of Rigid Bicyclic Dipeptidomimetics from Simple Dipeptides: Fused Imidazole Amino Acids

Gebhard Haberhauer; Frank Rominger

doi:10.1055/s-2003-38737

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Synlett 2003(6): 0780-0784
DOI: 10.1055/s-2003-38737

LETTER

Straightforward Synthesis of a Novel Class of Rigid Bicyclic Dipeptidomimetics from Simple Dipeptides: Fused Imidazole Amino Acids

Gebhard Haberhauer*, Frank Rominger
Organisch-Chemisches Institut, Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany
Fax: +49(6221)544205; e-Mail: gebhard.haberhauer@urz.uni-heidelberg.de;

Further Information

Publication History

Received 3 February 2003
Publication Date:
17 April 2003 (online)

Abstract
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Abstract

A novel class of rigid bicyclic dipeptidomimetics consisting of fused imidazole amino acids is presented. Their straightforward synthesis was realized by using simple dipeptides consisting of a diamino acid and threonine as starting material.

Key words

amino acids - condensation - cyclizations - heterocycles - peptides

References

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9

Crystal data for ( S , R )-9a: C₁₉H₂₀F₃N₃O₄, M = 411.38, colorless crystals(polyhedron), dimensions 0.46 ¥ 0.24 ¥ 0.22 mm³, crystal system monoclinic, space group P2₁, Z = 4, a = 9.0411(3) Å, b = 18.2239(6) Å, c = 11.5691(4) Å, α = 90°, β = 102.9450(10)°, γ = 90°, V = 1857.73 (11) Å³, ρ = 1.471 g/cm³, T = 200 (2) K, 2θ_max = 27.48°, radiation Mo Kα, λ = 0.71073 Å, 0.3° ω-scans with CCD area detector, covering a whole sphere in reciprocal space, 19250 reflections measured, 8436 unique [R(int) = 0.0220], 7545 observed [I >2σ(I)], intensities were corrected for Lorentz and polarization effects, an empirical absorption correction was applied using SADABS [11] based on the Laue symmetry of the reciprocal space, µ = 0.12 mm^-1, T_min = 0.95, T_max = 0.97, structure solved by direct methods and refined against F² with a Full-matrix least-squares algorithm using the SHELXTL-PLUS (5.10) software package, [12] 529 parameters refined, hydrogen atoms were treated using appropriate riding models, Flack absolute structure parameter 0.1(3), goodness of fit 1.01 for observed reflections, final residual values R1(F) = 0.030, wR2(F²) = 0.069 for observed reflections, residual electron density -0.18 to 0.18 eÅ^-3. CCDC 199868 contains the supplementary crystallographic data for this structure. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax:+44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk].

10

Crystal data for rac -7b: C₁₈H₂₁N₃O₄; M = 343.38, colorless crystals(polyhedron), dimensions 0.44 ¥ 0.22 ¥ 0.06 mm³, crystal system triclinic, space group P1, Z = 4, a = 7.3770(3) Å, b = 13.4649(5) Å, c = 17.9151(7) Å, α = 105.9240 (10)°, β = 91.5850 (10)°, γ = 90.7890 (10)°, V = 1710.15 (12) Å³, ρ = 1.334 g/cm³, T = 200(2) K, 2θ_max = 27.49°, radiation Mo Kα, λ = 0.71073 Å, 0.3° ω-scans with CCD area detector, covering a whole sphere in reciprocal space, 17922 reflections measured, 7814 unique [R(int) = 0.0383], 4622 observed (I >2σ(I)), intensities were corrected for Lorentz and polarization effects, an empirical absorption correction was applied using SADABS [11] based on the Laue symmetry of the reciprocal space, µ = 0.10 mm^-1, T_min = 0.96, T_max = 0.99, structure solved by direct methods and refined against F² with a Full-matrix least-squares algorithm using the SHELXTL-PLUS (5.10) software package [12] , 455 parameters refined, hydrogen atoms were treated using appropriate riding models, goodness of fit 1.02 for observed reflections, final residual values R1(F) = 0.051, wR2(F²) = 0.129 for observed reflections, residual electron density -0.29 to 0.57 eÅ^-3. CCDC 199869 contains the supplementary crystallographic data for this structure. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax:+44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk].

11

Program SADABS V2.03 for absorption correction: Sheldrick, G. M.; Bruker Analytical X-ray-Division, Madison, Wisconsin 2001.

12

Software package SHELXTL V5.10 for structure solution and refinement: Sheldrick, G. M.; Bruker Analytical X-ray-Division, Madison, Wisconsin 1997.