HBr and DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone) form a room-temperature-stable complex that provides a mild, effective, and selective hydrobrominating reagent toward alkynes, alkenes, and allenes. HBr–DMPU could also replace other halogenating reagents in the halo-Prins reaction, ether cleavage, and deoxybromination reactions.

No abstract

Islet transplantation has proven to be a viable treatment for individuals suffering from both Type 1 Diabetes Mellitus (T1D) and chronic pancreatitis. However, a variety of challenges limit the effectiveness of this procedure by reducing the number of islets that survive the harvesting and transplantation processes. Increasing islet survival would increase the longterm effectiveness of the procedure and allow this technique to be used in more patients. A number of factors have been shown to improve the outcomes of pancreatic islet transplantation, including immunological suppression and prevention of coagulation. In this review, we will discuss various chemical strategies reported in the literature for the preservation of islet graft function after transplantation, including islet encapsulation, the adoption of anti-inflammatory and immune suppressing molecules, and islet surface modification.

We previously demonstrated that the potent TLR4 inhibitor TAK-242 could be covalently conjugated to pancreatic islets using a linker that afforded an effective sustained delivery of the active drug after transplant. This drug-eluting tissue achieved local inhibition of TLR4-linked inflammation and proved beneficial to the islet graft survival. Here, we describe a new family of prodrugs with a modular design featuring a self-immolative para-aminobenzyl spacer bonded directly to the TAK-242 sulfonamide nitrogen, a tether for bioconjugation, and a β-eliminative arylsulfone "trigger". The inclusion of the para-aminobenzyl spacer affords a more stable prodrug which exhibits complex drug-release kinetics due to a two-stage release mechanism. This manuscript reports the preparation and characterization of several TAK-242 prodrugs fitted with different triggers and linkers and demonstrates that these second-generation prodrugs effectively release TAK-242 while avoiding nonproductive sulfonamide hydrolysis.