Synthesis of Easy-to-Functionalize Aza­bicycloalkane Scaffolds as Dipeptide Turn Mimics en Route to cRGD-Based Bioconjugates

In this paper we report the synthesis of new azabicycloalk- ane scaffolds, which could be exploited to obtain cRGD- based bioconjugates that may find promising application for targeted drug delivery, theranostic, and general cancer-cell labeling. By exploiting a Hosomi–Sakurai intramolecular allylation reaction we efficiently converted a silylated alde- hyde precursor into 7,5-fused lactam scaffolds endowed with an exocyclic double bond. The presence of the vinyl function should make it possible to conjugate bioactive compounds toselectively carry them to tumor sites. The optimized synthetic sequence allows the gram-scale preparation of the target scaffolds in a few steps and good 39 % overall yield from readily accessible materials. The high reactivity of the exo- cyclic olefin moiety was ascertained by performing a Heck coupling reaction with 1-bromo-4-nitrobenzene, which gave the corresponding functionalized derivatives in good (80– 91 %) yields.