Reduction of azides to primary amines in substrates bearing labile ester functionality. Synthesis of a PEG-solubilized, "Y"-shaped iminodiacetic acid reagent for preparation of folate-tethered drugs.
[formula: see text] Anhydride 3 is a useful reagent for the synthesis of triply linked drug conjugates. Examples using paclitaxel are provided. Conversion of the azido moiety to a primary amine in the presence of substrates bearing labile ester functionality requires the use of tin/mercaptan reducing system which includes methanol exchange equilibration to effect nitrogen-tin bond scission.
Lee
J W
JW
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.
Fuchs
P L
PL
D000588:Amines / Q000737:chemistry*; D000812:Anhydrides / Q000138:chemical synthesis*; D001386:Azides / Q000737:chemistry*; D004952:Esters / Q000737:chemistry; D005492:Folic Acid / Q000737:chemistry*; D007098:Imino Acids / Q000737:chemistry; D007202:Indicators and Reagents; D010078:Oxazines / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D017239:Paclitaxel / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry*
C410443:4-(2-(2-(2-azidoethyloxy)ethyloxy)ethyloxy)oxazine-2,6-dione; D000588:Amines; D000812:Anhydrides; D001386:Azides; D004952:Esters; D007098:Imino Acids; D007202:Indicators and Reagents; D010078:Oxazines; D011092:Polyethylene Glycols; D005492:Folic Acid; D017239:Paclitaxel; C008109:iminodiacetic acid