TY - JOUR
T1 - Trifluoroacetyl as a protecting group for HYNIC: stability in the presence of electrophiles and application in the synthesis of Tc-99m-radiolabelled peptides
AU - Surfraz, M. Bashir-Uddin
AU - King, Robert
AU - Mather, Stephen J.
AU - Biagini, Stefano C. G.
AU - Blower, Philip J.
PY - 2010/3/13
Y1 - 2010/3/13
N2 - TrifluoroacetylHYNIC-peptides have recently been shown to label directly with Tc-99m as efficiently as their non-trifluoroacetylated analogs. In this work, the trifluoroacetyl (Tfa) moiety has been evaluated as a protecting group for HYNIC against reaction with strong electrophiles. Fmoc-(trifluoroacetylHYNIC)-lysine, the chosen model starting material, was found to be resistant against acetaldehyde and benzylchloroformate challenges, at 1 mol equiv and a 1000 M excess, respectively. In contrast, the Fmoc(HYNIC)-lysine derivative, with a free hydrazine group, was quantitatively converted to the corresponding hydrazone after a 1 h incubation with acetaldehyde. Fmoc-(trifluoroacetylHYNIC)-lysine was also found to be stable over a wide pH range (3.6-10) to the acetaldehyde challenge. High efficiency Tc-99m-radiolabelling (99%) was achieved in the presence of acetaldehyde using Fmoc-(trifluoroacetylHYNIC)-lysine, as compared to a poor radiolabelling yield (34%) obtained with the non-trifluoroacetylated analog. These findings firmly establish the trifluoroacetyl group as a convenient and effective protecting group for HYNIC, and as a promising alternative to currently available labelling strategies. (C) 2010 Elsevier Ltd. All rights reserved.
AB - TrifluoroacetylHYNIC-peptides have recently been shown to label directly with Tc-99m as efficiently as their non-trifluoroacetylated analogs. In this work, the trifluoroacetyl (Tfa) moiety has been evaluated as a protecting group for HYNIC against reaction with strong electrophiles. Fmoc-(trifluoroacetylHYNIC)-lysine, the chosen model starting material, was found to be resistant against acetaldehyde and benzylchloroformate challenges, at 1 mol equiv and a 1000 M excess, respectively. In contrast, the Fmoc(HYNIC)-lysine derivative, with a free hydrazine group, was quantitatively converted to the corresponding hydrazone after a 1 h incubation with acetaldehyde. Fmoc-(trifluoroacetylHYNIC)-lysine was also found to be stable over a wide pH range (3.6-10) to the acetaldehyde challenge. High efficiency Tc-99m-radiolabelling (99%) was achieved in the presence of acetaldehyde using Fmoc-(trifluoroacetylHYNIC)-lysine, as compared to a poor radiolabelling yield (34%) obtained with the non-trifluoroacetylated analog. These findings firmly establish the trifluoroacetyl group as a convenient and effective protecting group for HYNIC, and as a promising alternative to currently available labelling strategies. (C) 2010 Elsevier Ltd. All rights reserved.
U2 - 10.1016/j.tet.2010.01.038
DO - 10.1016/j.tet.2010.01.038
M3 - Article
VL - 66
SP - 2037
EP - 2043
JO - TETRAHEDRON
JF - TETRAHEDRON
IS - 11
ER -