1429403-89-3Relevant articles and documents
Direct access to side chain N,N'-diaminoalkylated derivatives of basic amino acids suitable for solid-phase peptide synthesis
Pitteloud, Jean-Philippe,Bionda, Nina,Cudic, Predrag
, p. 321 - 333 (2013)
A simple and efficient one-pot procedure that enables rapid access to orthogonally protected N,N'-diaminoalkylated basic amino acid building blocks fully compatible with standard Boc and Fmoc solid-phase peptide synthesis is reported. Described synthetic approach includes double reductive alkylation of N α-protected diamino acids with N-protected amino aldehydes in the presence of sodium cyanoborohydride. This approach allows preparation of symmetrical, as well as unsymmetrical, basic amino acid derivatives with branched side-chains that can be further modified, enhancing their synthetic utility. The suitability of the synthesized branched basic amino acid building blocks for use in standard solid-phase peptide synthesis has been demonstrated by synthesis of an indolicidin analogue in which the lysine residue was substituted with the synthetic derivative N α -(9H-fluorenyl-9-methoxycarbonyl)-N β,N β ′-bis[2-(tert-butoxycarbonylamino)ethyl]-l-2,3-diaminopropionic acid. This substitution resulted in an analogue with more ordered secondary structure in 2,2,2-trifluoroethanol and enhanced antibacterial activity without altering hemolytic activity. Graphical abstract: [Figure not available: see fulltext.]
