An enantioselective synthesis of the key intermediate for triazole antifungal agents; application to the catalytic asymmetric synthesis of efinaconazole (Jublia).

A new synthetic route, the shortest reported to date, to access a key intermediate for the synthesis of various triazole antifungal agents was developed. The elusive tetrasubstituted stereogenic center that is essential in advanced triazole antifungal agents was constructed via the catalytic asymmetric cyanosilylation of a ketone. The subsequent transformations were performed in two one-pot operations, enhancing the overall synthetic efficiency toward the intermediate.

An enantioselective synthesis of voriconazole.

A new seven-step sequence to access voriconazole, a clinically used antifungal agent, was developed. The initial catalytic asymmetric cyanosilylation is the key to constructing the consecutive tetra- and trisubstituted stereogenic centers. The fluoropyrimidine unit frequently triggered unexpected side reactions, but careful amendment of the reaction sequence allowed for the concise enantioselective synthesis.

The development of a new windowless XEDS detector.

A new windowless X-ray energy-dispersive spectroscopy (XEDS) detector has been developed for an analytical electron microscope (AEM). Different from the conventional XEDS detectors, the new detector does not contain an ultra-thin window (UTW) and a vacuum gate valve which are the major causes of low X-ray detection sensitivity and vibration problems for AEM imaging, respectively. The performance of the newly designed detector was examined at an AEM column vacuum level of 10⁻⁵ Pa.

Third-order spherical aberration correction using multistage self-aligned quadrupole correction-lens systems.

New multistage self-aligned quadrupole correction-lens systems are proposed for correcting the spherical aberration of a rotationally symmetrical lens in a probe-forming system such as electron beam lithography and focused ion beam. These multistage correction-lens systems consist of six- or eight-stage electrostatic quadrupole and aperture electrodes placed between the quadrupoles. An octupole field for the correction of aperture aberration is automatically created and aligned with a quadrupole field by supplying a voltage to the aperture electrode.