Synthesis of Water-Soluble Cyclophane Pentamers Using Click Chemistry as a Multivalent Host for Daunorubicin and Doxorubicin

Abstract

Abstract Cationic cyclophane pentamer 1 has been prepared from a tetraazide-functionalized cyclophane derivative and four acetylene-functionalized cyclophane derivatives by Cu(I)-catalyzed 1,3-dipolar cycloadditions (click chemistry) in a 87% yield, followed by a treatment with trifluoroacetic acid. Cationic host 1 showed effective guest-binding behavior toward fluorescent guests such as 6-p-toluidinonaphthalene-2-sulfonate, in comparison with those of monomeric cyclophane. On the other hand, anionic cyclophane pentamer 2, which was derived from 1 by a reaction with succinic anhydride, showed enhanced guest-binding affinity toward anticancer drugs such as daunorubicin hydrochloride, in comparison with those of the monomeric cyclophane.