A convergent strategy for the stereoselective total synthesis of biologically active marine natural product biselyngbyolide B has been developed. Key strategies of this synthesis include Jamison protocol of trans-hydroalumination/allylation for installation of C18-C23 olefin moiety and intramolecular Heck coupling for macrocyclization.

The majority of theranostic prodrugs reported so far relay information through a fluorogenic response generated upon release of the active chemotherapeutic agent. A chemiluminescence detection mode offers significant advantages over fluorescence, mainly due to the superior signal-to-noise ratio of chemiluminescence. Here we report the design and synthesis of the first theranostic prodrug monitored by a chemiluminescence diagnostic mode. As a representative model, we prepared a prodrug from the chemotherapeutic monomethyl auristatin E, which was modified for activation by β-galactosidase. The activation of the prodrug in the presence of β-galactosidase is accompanied by emission of a green photon. Light emission intensities, which increase with increasing concentration of the prodrug, were linearly correlated with a decrease in the viability of a human cell line that stably expresses β-galactosidase. We obtained sharp intravital chemiluminescent images of endogenous enzymatic activity in β-galactosidase-overexpressing tumor-bearing mice. The exceptional sensitivity achieved with the chemiluminescence diagnostic mode should allow the exploitation of theranostic prodrugs for personalized cancer treatment.

Carbapenemase‐producing organisms (CPOs) pose a severe threat to antibacterial treatment due to the acquisition of antibiotic resistance. This resistance can be largely attributed to the antibiotic‐hydrolyzing enzymes that the bacteria produce. Current carbapenem “wonder drugs”, such as doripenem, ertapenem, meropenem, imipenem, and so on, are resistant to regular β‐lactamases, but susceptible to carbapenemases. Even worse, extended exposure of bacteria to these drugs accelerates the spread of resistance genes. In order to preserve the clinical efficacy of antibacterial treatment, carbapenem drugs should be carefully regulated and deployed only in cases of a CPO infection. Early diagnosis is therefore of paramount importance. Herein, we report the design, synthesis, and activity of the first carbapenemase‐sensitive chemiluminescent probe, CPCL, which may be used to monitor CPO activity. The design of our probe enables enzymatic cleavage of the carbapenem core, which is followed by a facile 1,8‐elimination process and the emission of green light through rapid chemical excitation. We have demonstrated the ability of the probe to detect a number of clinically relevant carbapenemases and the successful identification of CPO present in bacterial cultures, such as those used for clinical diagnosis. We believe that our use of “turn‐on” chemiluminescence activation will find significant application in future diagnostic assays and improve antibacterial treatment.

The first stereoselective total syntheses of marine cyclodepsipeptides, calcaripeptides A-C, have been accomplished. Emphasis was given particularly in identification of an efficient strategy for the macrocyclization. The notable features of our synthesis include Evans alkylation, Crimmins syn-aldol, Crimmins acetate aldol, Wittig olefination, and Shiina macrolactonization reactions. An anomaly in the (1)H NMR of the proposed calcaripeptide B has been amended during this synthetic study.

Adamantyl‐dioxetane luminophores are an important class of chemiluminescent molecular probes for diagnostics and imaging. We have developed a new efficient synthetic route for preparation of adamantyl‐enolether as precursors for dioxetane chemiluminescent luminophores. The synthesis is convergent, using an unusual Stille cross‐coupling reaction employing a stannane‐enolether, to directly afford adamantyl‐enolether. In a following simple step, the dioxetane is obtained by oxidation of the enolether precursor with singlet‐oxygen. The scope of this synthetic route is broad since a large number of haloaryl substrates are either commercially available or easily accessible. Such a late‐stage derivatization strategy simplifies the rapid exploration of novel luminogenic molecular structures in a library format and simplifies the synthesis of known dioxetane luminophores. We expect that this new synthetic strategy will be particularly useful in the design and synthesis of yet unexplored dioxetane chemiluminescent luminophores.