In this paper we report the synthesis of new azabicycloalkane 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 aldehyde 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 to selectively 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 exocyclic 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.

Oleocanthal, one of the minor components of the phenolic fraction isolated from extra virgin olive oil, is an effective inhibitor of COX enzymes, possessing similar potency to the NSAID ibuprofen. Moreover, it has the capacity to alter the structure of neurotoxic Aβ‐amyloid oligomers (ADDLs) and to change the structure of deformed microtubule‐associated tau–protein, thus inhibiting the formation of neurofibrillary tangles. It can have, therefore, potential therapeutic use for the treatment of neurodegenerative diseases. In this paper we describe the total synthesis of (±)‐oleocanthal in just 8 steps (9 % overall yield) from easily available starting materials. Moreover, resolution of the racemic mixture on an HPLC chiral column provided both enantiomers of oleocanthal in a single operation for biological studies.

7,5-Fused azabicycloalkane scaffolds, carrying a quaternary stereocenter at C3 position of the lactam ring, can act as effective reverse-turn mimics and have proven to be useful intermediates for the preparation of Arg-Gly-Asp (RGD)-based cyclopentapeptides (cRGD) with nanomolar activity as αβ/αβ integrin antagonists. Here, we report the synthesis of new azabicycloalkane scaffolds endowed at the C6 position with a para-substituted phenethyl side chain, which could be exploited to obtain cRGD-based bioconjugates that may find promising applications in anticancer therapy. By performing a domino cross enyne metathesis/ring-closing metathesis (CEYM/RCM) in the presence of styrene derivatives, followed by catalytic hydrogenation of the diene system, we easily converted a dipeptide precursor into the desired C6-functionalized azabicycloalkane scaffolds. The presence of a suitably protected p-amino group on the styrene moiety could be exploited, after deprotection, either to directly conjugate a bioactive compound or to introduce a suitable spacer between the cRGD unit and the bioactive compound.