Synthetic strategies for the incorporation of metallocenes into anti-infective scaffolds

With the rates of infectious diseases and (pan)drug-resistant pathogens constantly increasing, there is a pressing need for the development of new drug candidates. To fight this global health crisis, new medicines should propose improved or novel modes of action. A successful strategy to fight microbial resistance is the incorporation of metallocenes into drug scaffolds. This review aims at encouraging the scientific community to follow this approach by giving an overview of all published synthetic strategies either for the derivatization of anti-infective drug scaffolds with metallocenes or for the de novo synthesis of original metallocenyl anti-infectives. This should facilitate future research as published articles are classified depending on the reaction type that is employed for the incorporation of the metallocenes, namely addition-elimination, condensation, "click" chemistry, cross-coupling, nucleophilic substitution and other methods. Overall, this review exhibits the impressive but somewhat unexploited potential of anti-infective metallocenyl compounds to treat infectious diseases.