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Synthesis of Amino‐Acid–Nucleoside Conjugates
Author(s) -
Ghirardello Mattia,
Delso Ignacio,
Tejero Tomas,
Merino Pedro
Publication year - 2016
Publication title -
asian journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.846
H-Index - 44
eISSN - 2193-5815
pISSN - 2193-5807
DOI - 10.1002/ajoc.201600497
Subject(s) - chemistry , cycloaddition , click chemistry , combinatorial chemistry , triazole , alkyl , nucleoside , azide , amino acid , conjugate , nucleobase , conjugated system , organic chemistry , stereochemistry , catalysis , dna , biochemistry , mathematical analysis , polymer , mathematics
Representative derivatives of uridine‐conjugated amino acids that have been suitably protected for Fmoc solid‐phase chemistry have been prepared through efficient procedures that use “click” reactions as key steps, including thiol–ene radical reactions and copper‐catalyzed azide alkyne cycloaddition (CuAAC) reactions. Several linkers between the amino acid and nucleoside units, including alkyl chains and a triazole ring, have been successfully employed. Alkyl chains offer retention of flexibility, to allow the bisubstrate analogues to adopt an appropriate orientation, whilst the triazole ring can promote additional interactions at the active sites of target enzymes. Furthermore, a neutral surrogate of the pyrophosphate unit has been prepared by using a Staudinger–Vilarrasa reaction as a key step. Neutral analogues are promising surrogates for avoiding difficulties owing to cell‐membrane permeability.