Development of a manufacturing process toward the convergent synthesis of the COVID-19 antiviral Ensitrelvir

We describe the development of the practical manufacturing of Ensitrelvir, which was discovered as a SARS-CoV-2 antiviral candidate. Scalable synthetic methods of indazole, 1,2,4-triazole and 1,3,5-triazinone structures were established, and convergent couplings of these fragments enabled the development of a concise and efficient scale-up process to Ensitrelvir. In this process, introducing a meta-cresolyl moiety successfully enhanced the stability of intermediates. Compared to the initial route in the medicinal synthetic stage, the overall yield of the longest linear sequence (six steps) was improved by approximately 7-fold. Furthermore, nine out of the twelve isolated intermediates were crystallized directly from each reaction mixture without any extractive work-up (direct isolation). This led to an efficient and environmentally friendly manufacturing process that minimizes waste of organic solvents, reagents, and processing time. This practical process for manufacturing Ensitrelvir should contribute to protection against COVID-19

Concept design of the LiteBIRD satellite for CMB B-mode polarization

LiteBIRD is a candidate for JAXA's strategic large mission to observe the cosmic microwave background (CMB) polarization over the full sky at large angular scales. It is planned to be launched in the 2020s with an H3 launch vehicle for three years of observations at a Sun-Earth Lagrangian point (L2). The concept design has been studied by researchers from Japan, U.S., Canada and Europe during the ISAS Phase-A1. Large scale measurements of the CMB B-mode polarization are known as the best probe to detect primordial gravitational waves. The goal of LiteBIRD is to measure the tensor-to-scalar ratio (r) with precision of r < 0:001. A 3-year full sky survey will be carried out with a low frequency (34 - 161 GHz) telescope (LFT) and a high frequency (89 - 448 GHz) telescope (HFT), which achieve a sensitivity of 2.5 \u3bcK-arcmin with an angular resolution 30 arcminutes around 100 GHz. The concept design of LiteBIRD system, payload module (PLM), cryo-structure, LFT and verification plan is described in this paper

Low energy radioactivity BG model in Super-Kamiokande detector from SK-IV data

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Follow-up of GWTC-2 gravitational wave events with neutrinos from the Super-Kamiokande detector

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Combined Pre-Supernova Alert System with Kamland and Super-Kamiokande

International audiencePreceding a core-collapse supernova, various processes produce an increasing amount of neutrinos of all flavors characterized by mounting energies from the interior of massive stars. Among them, the electron antineutrinos are potentially detectable by terrestrial neutrino experiments such as KamLAND and Super-Kamiokande via inverse beta decay interactions. Once these pre-supernova neutrinos are observed, an early warning of the upcoming core-collapse supernova can be provided. In light of this, KamLAND and Super-Kamiokande have been monitoring pre-supernova neutrinos since 2015 and 2021, respectively. Recently, we performed a joint study between KamLAND and Super-Kamiokande on pre-supernova neutrino detection. A pre-supernova alert system combining the KamLAND detector and the Super-Kamiokande detector is developed and put into operation, which can provide a supernova alert to the astrophysics community. Fully leveraging the complementary properties of these two detectors, the combined alert is expected to resolve a pre-supernova neutrino signal from a 15 M$_{\odot}$ star within 510 pc of the Earth, at a significance level corresponding to a false alarm rate of no more than 1 per century. For a Betelgeuse-like model with optimistic parameters, it can provide early warnings up to 12 hours in advance