Photoinduced Chloroamination Cyclization Cascade with N-Chlorosuccinimide: From N-(Allenyl)sulfonylamides to 2-(1-Chlorovinyl)pyrrolidines.

Here, we present an intriguing photoinduced chloroamination cyclization of allenes bearing a tethered sulfonylamido group to afford 2-(1-chlorovinyl)pyrrolidines and related heterocycles in the presence of N-chlorosuccinimide (NCS) as the chlorine source. An in depth experimental and computational mechanistic study revealed the existence of multiple reaction pathways leading to a common nitrogen centered radical (NCR). This key NCR can be, in fact, originated from (a) the oxidation of the deprotonated allene by the photoexcited state of the Ru-catalyst and (b) the photodissociation of the in situ formed N-chloroallene. The NCR formation triggers an intramolecular cyclization to a highly reactive pyrrolidine vinyl radical, which upon chlorination delivers the final product. Thus, NCS plays a dual role, serving both as an activator of the sulfonamido functionality and as the chlorinating agent.

Unconventional approaches for the introduction of sulfur-based functional groups.

Organosulfur compounds have a pivotal role in the functionalities of many natural products, pharmaceuticals and organic materials. For these reasons, the search for new methodologies for the formation of carbon-sulfur bonds has been the object of intensive work for organic chemists. However, the proposed strategies suffer from various drawbacks, such as volatility, toxicity, and instability of the sulfur sources or the use of VOC solvents. In this review, we summarise the recent protocols which have the goal of obtaining sulfones, thioethers, thiazines, thiazepines and sulfonamides in an unconventional and/or sustainable way. The use of starting materials less invasive and toxic with respect to the traditional reagents, alternative solvents such as water, ionic liquids or deep eutectic solvents, the exploitation of ultrasound and electrochemistry, increasing the efficiency of the process, are reported. Moreover, representative reaction mechanisms are also discussed.

Raman Spectroscopy for Temporally Resolved Combustion Gas Diagnostics.

A novel approach for cost-effective and temporally resolved in-line combustion gas diagnostics based on spontaneous Stokes Raman spectroscopy is presented in this paper. The proposed instrument uses a multipass configuration designed to increase the scattering generation, giving information about gas species concentrations, including H2 and N2 that are not commonly available from analysis with absorption spectroscopy techniques. The system performs calibrated analysis providing both qualitative and quantitative information about the gas composition. Depending on the application, the device can work with spectra integration time from 0.15 s up to 10 s, with a Raman spectrum ranging from the H2 rotational peak at Raman shift of 587 cm-1 up to the H2 vibrational peak at 4156 cm-1, covering all the Raman emissions of major combustion species. The device response was characterized by a working pressure from 0.7 to 7.5 bar. The instrument prototype has been made completely transportable, designed to operate using a gas sampling system, and ready to be operated in relevant industrial in-line environments.

Trpm8 Expression in Human and Mouse Castration Resistant Prostate Adenocarcinoma Paves the Way for the Preclinical Development of TRPM8-Based Targeted Therapies.

Metastatic prostate cancer (mPCa) is one of the leading causes of cancer-related mortality in both the US and Europe. Androgen deprivation is the first-line therapy for mPCa; however, resistance to therapy inevitably occurs and the disease progresses to the castration resistant stage, which is uncurable. A definition of novel targeted therapies is necessary for the establishment of innovative and more effective protocols of personalized oncology. We employed genetically engineered mouse models of PCa and human samples to characterize the expression of the TRPM8 cation channel in both hormone naïve and castration resistant tumors. We show that Trpm8 expression marks both indolent (Pten-null) and aggressive (Pten/Trp53 double-null and TRAMP) mouse prostate adenocarcinomas. Importantly, both mouse and human castration-resistant PCa preserve TRPM8 protein expression. Finally, we tested the effect of TRPM8 agonist D-3263 administration in combination with enzalutamide or docetaxel on the viability of aggressive mouse PCa cell lines. Our data demonstrate that D-3263 substantially enhances the pro-apoptotic activity of enzalutamide and docetaxel in TRAMP-C1 e TRAMP-C2 PCa cell lines. To conclude, this study provides the basis for pre-clinical in vivo testing of TRPM8 targeting as a novel strategy to implement the efficacy of standard-of-care treatments for advanced PCa.