A class of ester–amide
oxanorbornadiene (EA-OND) molecules
was developed to release alcohol cargos by succinimide formation upon
addition of a thiol reagent. The resulting ring-closed adducts undergo
further fragmentation by retro-Diels–Alder reaction to release
a furan moiety in a manner similar to oxanorbornadiene diesters. The
rates of each of these fragmentation pathways in the same medium were
found to be sensitive to the steric nature of the amide substituent.
Alcohol release was much faster in protic solvents than in aprotic
ones, suggesting that this system may be useful for rapid response
to thiols in biological environments. Accordingly, the attachment
and thiol-dependent release of cholesterol was characterized as an
example of the manipulation of a drug-like cargo
