Synthesis of Cyclohexanones by a Tandem Photocatalyzed Annulation

The rapid synthesis of cyclic scaffolds is of high importance to the chemistry community. Strategies for the convergent synthesis of substi-tuted carbocycles and heterocycles remain underexplored despite the plethora of applications that these cyclic motifs have in the phar-maceutical and materials industries. Reported herein is a tandem carbene and photoredox-catalyzed process for the convergent synthesis of substituted cycloalkanones via a formal [5+1] cycloaddition. Featuring two distinct photoredox cycles and a novel α-oxidation of ben-zylic ketones, this reaction offers a mild approach to construct two contiguous C–C bonds and eliminates the need for strong bases or expensive metal catalysts. The utility of this method is highlighted through various product diversification reactions that allow access to a range of important cyclic scaffolds.

Vaccination uptake amongst older adults from minority ethnic backgrounds: A systematic review

Background Older adults from minority ethnic backgrounds are at increased risk of contracting COVID-19 and developing severe infection and have increased risk of mortality. Whilst an age-based vaccination approach prioritising older groups is being implemented worldwide, vaccine hesitancy is high amongst minority ethnic groups. Methods and findings We conducted a systematic review and convergent synthesis to systematically examine perceptions of vaccinations amongst older adults from minority ethnic backgrounds. We included studies that reported on perceptions, beliefs, and attitudes towards vaccinations in older adults aged ≥65 years from a minority ethnic background. We excluded studies of vaccinations in investigation or development, studies focused on specific medical conditions, studies where ethnic background or age group was unidentifiable, systematic reviews, editorials, and conference abstracts. We searched MEDLINE, Embase, Virtual Health Library, Web of Science, Cochrane Library, medRxiv, and PROSPERO databases from inception to 15 July 2021. Risk of bias for studies was assessed using the Mixed Methods Appraisal Tool. The quality of evidence of collective outcomes was estimated using the Grading of Recommendations Assessment, Development and Evaluation–Confidence in the Evidence from Reviews of Qualitative research (GRADE–CERQual) framework. A total of 28 eligible studies conducted between 1997 and 2020 were included in the final analysis (17 quantitative surveys, 8 focus group or interview studies, 2 mixed methods studies, and 1 case–control study). The majority were US studies in English or Spanish, except for 6 studies set in Hong Kong, 2 studies in Japan, 1 study in Brazil, and 1 multi-centre study (including China, Indonesia, Turkey, South Korea, Greece, UK, Brazil, and Nigeria). In total, 28,262 individuals with an estimated mean age of 69.8 years were included, 63.2% of whom were female. We summarised the common concepts and themes across studies and populations using a convergent synthesis analysis. Thirteen themes categorised as barriers or facilitators were identified and grouped into structural factors—healthcare provider and system related, patient related, and policy and operational—and were analysed by minority ethnic group. The main limitation of the study was the predominance of studies from the US and East Asia. Conclusions In this systematic review, we found that factors influencing vaccination uptake involve healthcare provider and system, patient-related, and governance-level factors that are specific to the older ethnic minority community being served. The evidence included in this review is supported by high or moderate certainty and can be translated to practice and policy. A tailored, multi-level approach combining increased education, access, and culturally competent discussions with trusted healthcare professionals to address health beliefs can maximise the potential impact of widespread vaccination policies.

Late-Stage C–H Arylation of Azepinoindole via Pd/Cu Catalysis: A Step Efficient and Convergent Synthesis of Rucaparib

The C–H arylation of indoles holds the promise to shorten synthetic routes in the production of pharmaceuticals. However, late-stage C–H activation reactions often rely on the presence of protecting groups or stoichiometric metal additives. The regiospecific C–H arylation of a highly functionalized azepino[5,3,4-cd]indole scaffold lacking directing groups via Pd(II) and Cu(II) co-catalysis is reported. The direct C–H coupling was demonstrated in the convergent synthesis of rucaparib, an FDA approved anticancer drug.

Scalable convergent synthesis of therapeutic oligonucleotides

The recent explosive growth in the number of oligonucleotide clinical development programs and drug approvals underscores their ability to treat diseases via mRNA regulation. Currently, solid-supported synthesis is limited to ≤ 5 kg (~ 1 mole) batch sizes and the feasibility of liquid-phase syntheses to supply materials of sufficient purity and amount for clinical trials has not been proven. Herein we describe the first convergent synthesis of a full-length 18-mer mixed backbone (PO/PS) 2’-MOE gapmer oligonucleotide by the phosphoramidite approach suitable for use in clinical trials. Techniques described to control impurities during its synthesis can be implemented in common active pharmaceutical ingredient (API) manufacturing facilities and should enable a >10-fold increase in production batch scaling.