Beyond simple proton transfer processes: domino reactions between 4-substituted indoles and nitroethene as a new gateway to ergot alkaloids

The multimodal biology activity of ergot alkaloids is known by humankind since middle ages. Synthetically modified ergot alkaloids are used for the treatment of various medical conditions. Despite the great progress in organic syntheses, the total synthesis of ergot alkaloids remains a great challenge due to the complexity of their polycyclic structure with multiple stereogenic centres. This project has developed a new domino reaction between indoles bearing a Michael acceptor at the 4 position and nitroethene, leading to potential ergot alkaloid precursors in highly enantioenriched form. The reaction was optimised and applied to a large variety of substrate with good results. Even if unfortunately all attempts to further modify the obtained polycyclic structure failed, it was found a reaction able to produce the diastereoisomer of the polycyclic product in excellent yields. The compounds synthetized were characterized by NMR and ESIMS analysis confirming the structure and their enantiomeric excess was determined by chiral stationary phase HPLC. The mechanism of the reaction was evaluated by DFT calculations, showing the formation of a key bicoordinated nitronate intermediate, and fully accounting for the results observed with all substrates. The relative and absolute configuration of the adducts were determined by a combination of NMR, ECD and computational methods.

A new concept for a Sport-Coupè car developed with the Industrial Design Structure method (IDeS)

The aim of this study, conducted in collaboration with Lawrence Technological University in Detroit, is to create, through the method of the Industrial Design Structure (IDeS), a new concept for a sport-coupe car, based on a restyling of a retro model (Ford Mustang 1967). To date, vintage models of cars always arouse great interest both for the history behind them and for the classic and elegant style. Designing a model of a vehicle that can combine the charm of retro style with the innovation and comfort of modern cars would allow to meet the needs and desires of a large segment of the market that today is forced to choose between past and future. Thanks to a well-conceived concept car an automaker company is able to express its future policy, to make a statement of intent as, such a prototype, ticks all the boxes, from glamour and visual wow-factor to technical intrigue and design fascination. IDeS is an approach that makes use of many engineering tools to realize a study developed on several steps that must be meticulously organized and timed. With a deep analysis of the trends dominating the automotive industry it is possible to identify a series of product requirements using quality function deployment (QFD). The considerations from this first evaluation led to the definition of the technical specifications via benchmarking (BM) and top-flop analysis (TFA). Then, the structured methodology of stylistic design engineering (SDE) is applied through six phases: (1) stylistic trends analysis; (2) sketches; (3) 2D CAD drawings; (4) 3D CAD models; (5) virtual prototyping; (6) solid stylistic model. Finally, Developing the IDeS method up to the final stages of Prototypes and Testing you get a product as close as possible to the ideal vehicle conceptualized in the initial analysis.