Lithiation at the 2-position of purine ring has been accomplished for the first time by using 6-chloro-9-(2,3-O-isopropylidene-5-O-trityl-β-d-ribofuranosyl)-8-(triisopropylsilyl)purine (7) as a substrate and LTMP as a lithiating agent. The 8-triisopropylsilyl group in 7 did not undergo anionic migration and, thus, allowed the ready generation of the C2-lithiated species by preventing deprotonation at the 8-position. The electron-withdrawing 6-chlorine atom plays an essential role to this C2-lithiation. Reactions of the lithiated species with electrophiles gave the 2-substituted products (Me, Et, i-Pr, CH(OH)C6H11, C(OH)Me2, CHO, CO2Me, and I) mostly in good yields. Ammonolysis of the 6-chlorine atom of these products (heating at 110 °C in a sealed tube with NH3/MeOH) effected simultaneous desilylation at the 8-position to give the corresponding adenosine analogues. The whole sequence provides a new and highly general method for the synthesis of 2-substituted adenosines.

Background: Patients who develop severe side-effects when taking high-risk drugs may have a significantly reduced health-related quality of life (QOL); therefore, it is important to identify changes in health-related QOL in these patients. This study aimed to determine health-related QOL in community pharmacy outpatients taking high-risk drugs.Methods: This prospective observational study was conducted at 29 pharmacies in 12 regions and cities in Japan from October to December 2020. Using descriptive questionnaires of EuroQOL-5-dimensions-5-levels (EQ-5D-5L), community pharmacists obtained health-related QOL data from outpatients taking high-risk drugs.Results: In total, 760 outpatients were enrolled. The mean health-related QOL of all outpatients was 0.869. Health-related QOL decreased with increasing age. Outpatient health -related QOL was 0.700, 0.763, 0.785, and 0.817 when taking antiepileptic, antidepressant, digitalis, and antiarrhythmic drugs, respectively, which was lower than the average health-related QOL of all outpatients. Mobility and pain/discomfort accounted for a large proportion of the decline in health-related QOL with increasing age. No difference was found concerning personal care in relation to age; however, the number of outpatients with mobility, normal activity, and pain challenges decreased with age. In contrast, outpatients aged <65 years with anxiety/depression showed lower than overall average health-related QOL.Conclusion: Community pharmacists determined the health-related QOL of outpatients taking high-risk drugs. We clarified the contributions of the 5-dimensions.Trial registration: UMIN-CTR Study Design: trial Number UMIN 000041942. Registered 30 September 2020, https://www.umin.ac.jp

Recent changes in the environment surrounding community pharmacists include follow-up after dispensing becoming mandatory, initiation of certified pharmacy system with specific functions, with the discussions on post-graduate training, lifelong training and specialization, refill of prescriptions, as well as pros and cons of hospital pharmacies in preparation for the 2022 dispensing fee revision. In this regard, since 2019, I have been receiving training at The Cancer Institute Hospital of Japanese Foundation for Cancer Research (JFCR). In addition, to implementing community pharmacists perspectives into collaboration between community pharmacists and hospital pharmacists, a tracing report model incorporating the Common Terminology Criteria for Adverse Events (CTCAE) ver. 5.0 has been created. And, a regimen of drugs and operation describing necessary supportive care has been published in The Cancer Institute Hospital of JFCR website. As a practice of patient safety management at pharmacies, we are working on the standardization of questionnaire criteria to assess the severity of adverse medication reactions in cancer patients and the measurement of health-related quality of life using EuroQol 5 dimensions 5-level (EQ-5D-5L), introduced with cooperation of universities, hospitals, and pharmacies. As medical care is advancing day by day, especially in cancer medication therapy, patient safety management by pharmacists becomes essential, when dealing with the complexity of administration schedule and the wide variety of side effects. For patient safety management, community pharmacists need to practice with pharmaceutical and medical knowledge, and have skills to acquire and convey information, with a researcher s perspective.

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