Synthesis of sansalvamide A peptidomimetics: triazole, oxazole, thiazole, and pseudoproline containing compounds

TETRAHEDRON

卷:68

Article

Davis, Melinda R.²  Singh, Erinprit K.²  Wahyudi, Hendra¹  Alexander, Leslie D.²  Kunicki, Joseph B.²  Nazarova, Lidia A.²  Fairweather, Kelly A.³  Giltrap, Andrew M.³  Jolliffe, Katrina A.³  McAlpine, Shelli R.¹ 

[1] Univ New S Wales, Sch Chem, Kensington, NSW 2052, Australia

[2] San Diego State Univ, Dept Chem & Biochem, San Diego, CA 92182 USA

[3] Univ Sydney, Sch Chem, Sydney, NSW 2006, Australia

关键词: Peptide;    Macrocycle;    Peptidomimetic;    Sansalvamide A;    Triazole;    Oxazole;    Thiazole;    Pseudoproline;   

DOI  :  10.1016/j.tet.2011.11.089

来源: Elsevier

【 摘 要 】

Peptidomimetic-based macrocycles typically have improved pharmacokinetic properties over those observed with peptide analogs. Described are the syntheses of 13 peptidomimetic derivatives that are based on active sansalvamide A structures, where these analogs incorporate heterocycles (triazoles, oxazoles, thiazoles, or pseudoprolines) along the macrocyclic backbone. The syntheses of these derivatives employ several approaches that can be applied to convert a macrocyclic peptide into its peptidomimetic counterpart. These approaches include peptide modifications to generate the alkyne and azide for click chemistry, a serine conversion into an oxazole, a Hantzsch reaction to generate the thiazole, and protected threonine to generate the pseudoproline derivatives. Furthermore, we show that two different peptidomimetic moieties, triazoles, and thiazoles, can be incorporated into the macrocyclic backbone without reducing cytotoxicity: triazole and thiazole. (C) 2011 Elsevier Ltd. All rights reserved.

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