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Solid-phase synthesis of cyclic lipopeptidotriazoles

The solid-phase synthesis of cyclic lipopeptidotriazoles derived from the cyclic decapeptide c(Lys-Lys(2)-Leu-Lys-Lys(5)-Phe-Lys-Lys-Leu-Gln) (BPC194), incorporating a triazolyl ring at Lys(2) and a hexanoyl group at Lys(5), was studied. Four different strategies that required the use of five orthogonal protecting groups (Fmoc, tBu, All, pNZ, ivDde) were explored. The influence of the side-chain protection of Lys(2) and Lys(5) with the ivDde and pNZ groups was evaluated by incorporating Lys(2)(ivDde)/Lys(5)(pNZ) or Lys(2)(pNZ)/Lys(5)(ivDde). The order of removal of these protecting groups and of the introduction of the hexanoyl and triazolyl moieties was also studied. The best strategy included: (i) synthesis of a cyclic peptidyl resin bearing Lys(2)(ivDde) and Lys(5)(pNZ); (ii) pNZ group removal; (iii) acylation with hexanoic acid; (iv) ivDde group removal; and (v) acylation with propiolic acid followed by an azide-alkyne 1,3-dipolar cycloaddition. By using this protocol, a set of cyclic lipopeptidotriazoles was prepared in high purities

S. V. is a recipient of a predoctoral fellowship from the Generalitat de Catalunya. This work was supported by grants from the Spanish Ministerio de Economia y Competitividad (MINECO) (AGL2009-13255-C02-02/AGR and AGL2012-39880-C02-02)

© European Journal of Organic Chemistry, 2014, vol. 22, p. 4785-4794

Wiley-VCH Verlag

Author: Vilà Roura, Sílvia
Camó Marin, Cristina
Figueras, Eduard
Badosa Romañó, Esther
Montesinos Seguí, Emilio
Planas i Grabuleda, Marta
Feliu Soley, Lídia
Date: 2014 August
Abstract: The solid-phase synthesis of cyclic lipopeptidotriazoles derived from the cyclic decapeptide c(Lys-Lys(2)-Leu-Lys-Lys(5)-Phe-Lys-Lys-Leu-Gln) (BPC194), incorporating a triazolyl ring at Lys(2) and a hexanoyl group at Lys(5), was studied. Four different strategies that required the use of five orthogonal protecting groups (Fmoc, tBu, All, pNZ, ivDde) were explored. The influence of the side-chain protection of Lys(2) and Lys(5) with the ivDde and pNZ groups was evaluated by incorporating Lys(2)(ivDde)/Lys(5)(pNZ) or Lys(2)(pNZ)/Lys(5)(ivDde). The order of removal of these protecting groups and of the introduction of the hexanoyl and triazolyl moieties was also studied. The best strategy included: (i) synthesis of a cyclic peptidyl resin bearing Lys(2)(ivDde) and Lys(5)(pNZ); (ii) pNZ group removal; (iii) acylation with hexanoic acid; (iv) ivDde group removal; and (v) acylation with propiolic acid followed by an azide-alkyne 1,3-dipolar cycloaddition. By using this protocol, a set of cyclic lipopeptidotriazoles was prepared in high purities
S. V. is a recipient of a predoctoral fellowship from the Generalitat de Catalunya. This work was supported by grants from the Spanish Ministerio de Economia y Competitividad (MINECO) (AGL2009-13255-C02-02/AGR and AGL2012-39880-C02-02)
Format: application/pdf
ISSN: 1434-193X (versió paper)
1099-0690 (versió electrònica)
Document access: http://hdl.handle.net/10256/10935
Language: eng
Publisher: Wiley-VCH Verlag
Collection: MICINN/PN 2013-2015/AGL2012-39880-C02-02
MICINN/PN 2010-2012/AGL2009-13255-C02-02
Reproducció digital del document publicat a: http://dx.doi.org/10.1002/ejoc.201402111
Articles publicats (D-Q)
Is part of: © European Journal of Organic Chemistry, 2014, vol. 22, p. 4785-4794
Rights: Tots els drets reservats
Subject: Pèptids -- Síntesi
Peptides -- Synthesis
Compostos orgànics -- Síntesi
Organic compounds -- Synthesis
Compostos heterocíclics -- Síntesi
Heterocyclic compounds -- Synthesis
Title: Solid-phase synthesis of cyclic lipopeptidotriazoles
Type: info:eu-repo/semantics/article
Repository: DUGiDocs

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