Johan Wennerberg

Herein, we report a concise formal synthesis of (±)-isoalantolactone through a six-step route to the advanced intermediate of Tada. The 5/6/6-fused eudesmanolide core is assembled through a SmI2-mediated reductive lactonization, while a late-stage acid-promoted sequence combines global deprotection, intramolecular aldol condensation, and thermodynamic stereochemical convergence to establish the required relative stereochemistry. Computational analysis supports thermodynamically controlled formation of the observed diastereomer and validates the overall synthetic design.

α‐deuterated carboxylic acids have been synthesized from the corresponding malonic acids via hydrogen/deuterium exchange and decarboxylation in presence of D₂O. The method is general, mild and efficient and does not require organic solvents or other additives. Yields range between 83% and 94% and purification was not necessary. Starting materials were easy accessible and the α‐deuterated carboxylic acids may easily be transformed to other labeled compounds such as alcohols, aldehydes, esters, and amides. Characterization with NMR confirmed purity and isotopic purity.

Despite the significant progress in anticancer drug development over recent years, there is a vital need for newer agents with unique, but still effective, mechanisms of action in order to treat the disease, particularly the highly aggressive and drug-resistant types. Alkylating agents, in particular nitrogen-based alkylators, are commonly used to treat hematological and solid malignancies; they exert their antineoplastic effects at all phases of the cell cycle and prevent reproduction of tumor cells. Certain alkylating agents have been designed to be more lipophilic, enabling the compound to penetrate the cell and enhance its alkylating activity against tumors. This review details the evolution of currently available alkylating agents and their profiles, with a focus on nitrogen-based alkylating agents, as important anticancer therapy strategies.

This study investigated the feasibility of targeting the free, unbound forms of prostate-specific antigen (fPSA) for in vivo imaging of prostate adenocarcinomas (PCa), as PSA is produced and secreted at abundance during every clinical stage and grade of PCa, including castration-resistant disease. We injected ¹²⁵I-labeled monoclonal antibody PSA30 (specific for an epitope uniquely accessible on fPSA alone) intravenously in male nude mice carrying subcutaneous xenografts of LNCaP tumors (n=36). Mice were sacrificed over a time course from 4 hours to 13 days after injecting ¹²⁵I-labeled PSA30. Tissue uptake of ¹²⁵I-PSA30 at 48 and 168 hours after intravenous injection was compared with two clinically used positron emission tomography radiopharmaceuticals, ¹⁸F-fluoro-deoxy-glucose (¹⁸F-FDG) or ¹⁸F-choline, in cryosections using Digital AutoRadiography (DAR) and also compared with immunohistochemical staining of PSA and histopathology. On DAR, the areas with high ¹²⁵I-PSA30 uptake corresponded mainly to morphologically intact and PSA-producing LNCaP cells, but did not associate with the areas of high uptake of either ¹⁸F-FDG or ¹⁸F-choline. Biodistribution of ¹²⁵I-PSA30 measured in dissected organs ex vivo during 4 to 312 hours after intravenous injection demonstrated maximum selective tumor uptake 24–48 hours after antibody injection. Our data showed selective uptake in vivo of a monoclonal antibody highly specific for fPSA in LNCaP cells. Hence, in vivo imaging of fPSA may be feasible with putative usefulness in disseminated PCa.