Development of Continuous Flow Sonogashira Coupling of lead Anti-Cancer Small Molecule Inhibitors for Potential Treatment of Acute Myeloid Leukemia

As the technology for science develops, the research strategy in medicines and therapeutics also improves. In this paper, I will cover the process of Sonogashira cross-coupling and Amide Coupling reaction for an anticancer agent in both batch and flow chemistry. Continuous Flow Chemistry has advantages such as being more efficient, safer, and faster. This paper studies the synthesis of HSNO608, an anticancer lead compound for Acute Myeloid Leukemia (AML), which has a specific potent activity to FTL3 Kinase. Inhibition of FLT3 Kinase leads to inhibition of downstream pathways such as MPK and P13K pathways. In this two-step experiment, the Sonogashira cross-coupling reaction is a crucial step in the flow process. For the amidation reaction, it favored high retention time and low temperatures. For the Sonogashira cross-coupling reactions, different types of Palladium Catalyst and Copper Co-catalyst were screened. The best catalyst found was PdCl2(MeCN)2 with the ligand of [(t-Bu)3PH]BF4 giving us a yield of 88% with high loading (%10) of Copper and Pd catalyst. This condition was further optimized to reduce the catalyst loading to 1%. In conclusion, we were able to optimize and create methods to synthesize lead medicinal compounds. In the future, this approach could be applied to other anticancer targets and other medicinal chemical targets

Results of the Excitation Test of the LHD Helical Coils Cooled by Subcooled Helium

Large helical device, the largest superconducting stellarator, has been operated for the research of fusion plasma since 1998. The toroidal field of almost 3 T is produced by a pair of pool-cooled helical coils, in the innermost layers of which a normal-zone had been induced several times at the bottom of the coil at higher currents than 11.0 kA. Since the field is not the highest there, the local cooling conditions are probably deteriorated by bubbles gathered by buoyancy. In order to improve the cryogenic stability by subcooling, an additional cooler with two-stage cold compressors was installed at the inlet of the coil in 2006. The inlet and outlet temperatures of the coils were successfully lowered to 3.2 K and 3.8 K, respectively, with a mass flow of 50 g/s. In spite of a half charging rate to reduce AC losses, a normal-zone was induced near the top of the coil at 11.45 kA. It propagated to one side and stopped near the inner equator, where the field is the highest. In comparison with the stability tests with a model coil, the local temperatures of the innermost layers near the top is considered to have been raised up to almost the saturated temperature of 4.4 K by charging. The excitation method was revised to waiting cool-down at 11.0 kA, and the excitations up to 11.5 kA have been attained