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. 2014 Jul 1;5(7):949-952.
doi: 10.1039/C4MD00162A.

Ugi 4-CR Synthesis of γ- and δ-Lactams providing new access to diverse enzyme interactions, a PDB analysis

André Boltjes  1 , George P Liao  1 , Ting Zhao  1 , Eberhardt Herdtweck  2 , Alexander Dömling  3
Affiliations

Ugi 4-CR Synthesis of γ- and δ-Lactams providing new access to diverse enzyme interactions, a PDB analysis

André Boltjes et al. Medchemcomm. .

Abstract

A three step synthesis of N-unsubstituted tetrazolo γ- and δ-lactams involving a key Ugi-4CR is presented. The compounds, otherwise difficult to access, are conveniently synthesized in overall good yields by our route. PDB analysis of the N-unsubstituted γ- and δ-lactam fragment reveals a strongly tri-directional hydrogen bond donor acceptor interaction with the amino acids of the binding sites.

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Figures

Fig. 1
Fig. 1
Triforcated hydrogen bonding interactions (red dotted lines) of an N-unsubstituted γ-lactam (cyan sticks) with some protease amino acids in the example of rupintrivir (PDB ID 1CQQ).
Fig. 2
Fig. 2
Intermolecular hydrogen bond network of exemplary γ- and δ-lactams in the solid state. Molecule 6a shows a pair wise hydrogen bonding with a neighbour molecule, while 6f shows a bifurcated hydrogen bonding pattern including a neighbour molecule and a water molecule.
Fig. 3
Fig. 3
Above: Alignment of several PDB structures showing the polar interactions for 10 γ-lactam containing ligands. The ligand γ-lactam moiety is shown as green sticks, the interacting receptor amino acids as colored lines and the hydrogen bonding as yellow dotted lines.
Scheme 1
Scheme 1
Devised synthetic pathway to tetrazolo N-unsubstituted γ- and δ-lactams
Scheme 2
Scheme 2
The two aldehydes utilized in the Ugi tetrazole synthesis.
See this image and copyright information in PMC

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References

    1. Tang C, Castoldi AF, Costa LG. Biochem. Mol. Biol. Int. 1993;29:1047. - PubMed
    2. Zhang X, et al. Antiviral Red. 2013;97:264–269. - PubMed
    3. Chem. 2006;118:1–5.
    4. Angew. Chem. Int. Ed. 2006;45:1.
    1. Zhang X, et al. World J. Gastroenterol. 2010;16:201. - PMC - PubMed
    1. Matthews DA, et al. PNAS. 1999;96:11000. - PMC - PubMed
    1. Koes D, et al. PLoS ONE. 2012;7:e32839. - PMC - PubMed
    1. Dömling A. Chem. Rev. 2006;106:17. - PubMed

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