Unearthing the Subtleties of Rhodium(II)-Catalyzed Carbenoid Cycloadditions to Furans with an N-Sulfonyl-1,2,3-triazole Probe.

The rhodium(II)-catalyzed reaction of a model alkenyl donor/acceptor N-sulfonyltriazole with a wide selection of furans is reported. This investigation unearthed a range of structurally diverse carbocyclic and ring-opened products, in good to excellent yields. The products obtained are proposed to arise selectively via cyclopropanation or zwitterionic rearrangement pathways, which are highly dependent on both the structural and electronic features of the furan substrate.

Synthetic Tigliane Intermediates Engage Thiols to Induce Potent Cell Line Selective Anti-Cancer Activity.

The tigliane ring system, which encompasses iconic members such as phorbol and TPA, is widely renowned due to numerous observations of displaying potent biological activity, and subsequent use as mainstream biochemical tools. Traditionally, naturally occurring phorboids are regarded as tumor promotors through PKC activation, although in recent times more highly oxidized natural derivatives have been identified as anti-tumor agents. In the view that only limited synthetic investigations toward skeletal stereochemical modification have been undertaken, non-natural systems could be useful for a better understanding of the tigliane pharmacophore via interrogation of cellular sensitivity. In this context the concise construction of a number of highly functionalized non-natural D-ring inverted phorbol esters were synthesized, via a rhodium-catalyzed [4+3] cycloaddition, and biologically evaluated using a range of cancer cell lines. The biological results highlight the notion that subtle changes in structure have dramatic effects on potency. Furthermore, although the non-natural derivatives did not outcompete the natural systems in the PKC-activation sensitive MCF7 cancer cell line, they outperformed in other cancer cell lines (MM96L and CAL27). This observation strongly suggested an alternate mode of action not involving activation of PKC, but instead involves thiol addition as indicated by glutathione addition and NF-κB reporter activity.

Ranking Oxidant Sensitiveness: A Guide for Synthetic Utility.

Common oxidants used in chemical synthesis, including newly developed perruthenates, were evaluated in the context of understanding (and better appreciating) the sensitiveness and associated potential hazards of these reagents. Analysis using sealed cell differential scanning calorimetry (scDSC) facilitated Yoshida correlations, which were compared to impact sensitiveness and electrostatic discharge experiments (ESD), that enabled sensitiveness ranking. Methyltriphenylphoshonium perruthenate (MTP3, 8), isoamyltriphenylphosphonium perruthenate (ATP3, 7) and tetraphenylphosphonium perruthenate (TP3, 9) were found to be the most sensitive followed by 2-iodoxybenzoic acid (IBX, 2) and benzoyl peroxide (BPO, 10), whereas the most benign were observed to be Oxone (12), manganese dioxide (MnO2 , 13), and N-bromosuccinimide (NBS, 17).