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Solid‐Phase Synthesis of Cyclic Lipopeptidotriazoles
Author(s) -
Vilà Sílvia,
Camó Cristina,
Figueras Eduard,
Badosa Esther,
Montesinos Emilio,
Planas Marta,
Feliu Lidia
Publication year - 2014
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201402111
Subject(s) - chemistry , acylation , alkyne , stereochemistry , organic chemistry , catalysis
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, t Bu, 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.