Medicinally Privileged Sultams: Synthesis and Mechanisms of Action

: To date, more than a thousand research articles have been published detailing various regio-, stereo-, chemo-, and enantioselective specific synthesis of the cyclic sulfonamides (sultams). Although, enormous synthetic efforts were made but bioactivities of sultams have not been widely investigated. Sultams are the sulfur analogs of lactams (cyclic amides) which demonstrated a broad range of medicinal activity and several lactam drugs are commercially available. In contrast, only a few sultam drugs are commercially available while the presence of two oxygens on sulfur in sultam motifs can serve as a better H-bond acceptor than lactam scaffolds. One of the major objectives of this mini-review is to draw appropriate attention from the medicinal/pharmaceutical chemists to conduct in-depth research on sultam derivatives targeted to the development of new drugs. This article abridges synthesis, potential bioactivity, and mechanisms of therapeutic action of four to seven-membered sultam derivatives. Based on the available literature, this is the first effort to consolidate only the medicinally privileged sultam molecules and drugs under the same umbrella. While every effort was taken to comprise all the relevant reports related to bioactive sultams, any oversight is truly unintentional.

Synthesis of chiral seven-membered cyclic sulfonamides through palladium-catalyzed arylation of cyclic imines

An enantioselective palladium-catalyzed addition of arylboronic acids to seven-membered cyclic N-sulfonyl aldimines and ketimines has been developed, giving the chiral cyclic sulfonamides with excellent yields and up to 99% ee.