At last count, nearly 5000 halogenated natural products have been discovered. In approximately half of these compounds, the carbon atom to which the halogen is bound is sp3‐hybridized; therefore, ...there are an enormous number of natural products for which stereocontrolled halogenation must be a critical component of any synthesis strategy. In this Review, we critically discuss the methods and strategies used for stereoselective introduction of halogen atoms in the context of natural product synthesis. Using the successes of the past, we also attempt to identify gaps in our synthesis technology that would aid the synthesis of halogenated natural products, as well as existing methods that have not yet seen application in complex molecule synthesis. The chemistry described herein demonstrates yet again how natural products continue to provide the inspiration for critical advances in chemical synthesis.
With thousands of natural products containing halogen‐bearing stereogenic centers, a wealth of methods have been developed for their stereocontrolled introduction in the context of total synthesis. This Review highlights the creative ways in which organic chemists have dealt with the challenges of stereochemically rich, halogenated natural products.
The rate of detection of thyroid nodules and carcinomas has increased with the widespread use of ultrasonography (US), which is the mainstay for the detection and risk stratification of thyroid ...nodules as well as for providing guidance for their biopsy and nonsurgical treatment. The Korean Society of Thyroid Radiology (KSThR) published their first recommendations for the US-based diagnosis and management of thyroid nodules in 2011. These recommendations have been used as the standard guidelines for the past several years in Korea. Lately, the application of US has been further emphasized for the personalized management of patients with thyroid nodules. The Task Force on Thyroid Nodules of the KSThR has revised the recommendations for the ultrasound diagnosis and imaging-based management of thyroid nodules. The review and recommendations in this report have been based on a comprehensive analysis of the current literature and the consensus of experts.
During the coronavirus disease (COVID-19) pandemic, social distancing was effective in controlling disease spread across South Korea. The impact of national social distancing on the spread of common ...respiratory virus infections has rarely been investigated. We evaluated the weekly proportion of negative respiratory virus polymerase chain reaction (PCR) test results and weekly positive rates of each respiratory virus during the social distancing period (10th-41st weeks of 2020) and the corresponding period in different years, utilizing the national respiratory virus surveillance dataset reported by the Korean Center for Disease Control and Prevention. The proportions of negative respiratory virus PCR test results increased up to 87.8% and 86.1% during level 3 and level 2 of the social distancing period, respectively. The higher the level of social distancing, the higher the proportion of negative respiratory virus PCR test results. During the social distancing period, the mean weekly positive rates for parainfluenza virus, influenza virus, human coronavirus, and human metapneumovirus were significantly lower than those during the same period in 2015-2019 (0.1% vs. 9.3%, P <0.001; 0.1% vs. 7.2%, P <0.001; 0.4% vs. 2.3%, P <0.001; and 0.2% vs. 5.3%, P <0.001, respectively). The mean positive rate for rhinovirus/enterovirus during level 3 social distancing was lower than that in the same period in 2015-2019 (8.5% vs. 19.0%, P <0.001), but the rate during level 1 social distancing was higher than that in the same period in 2015-2019 (38.3% vs. 19.4%, P <0.001). The national application of social distancing reduced the spread of common respiratory virus infections during the COVID-19 pandemic.
Previously available ketyl radical cyclization conditions suffer from low and uncontrollable diastereoselectivity because of the absence of reagent–substrate interactions. In this report, ...stereochemical modulation was accomplished by taking advantage of the pyridine-boryl radical, which leaves the synthetically modifiable boronate moiety on the carbonyl oxygen near the reacting center during the stereo-determining cyclization step. In consequence, a catalytic diastereoselective synthesis of
trans
-2-substituted-1-indanols was achieved in the presence of a sterically congested six-membered diboronic ester and an efficient hydrogen atom donor.
Whereas the conventional anti-dihalogenation of alkenes is a valuable synthetic tool with highly predictable stereospecificity, the restricted reaction mechanism makes it challenging to alter the ...diastereochemical course into the complementary syn-dihalogenation process. Only a few notable achievements were made recently by inverting one of the stereocenters after anti-addition using a carefully designed reagent system. Here, we report a conceptually distinctive strategy for the simultaneous double electrophilic activation of the two alkene carbons from the same side. Then, the resulting vicinal leaving groups can be displaced iteratively by nucleophilic halides to complete the syn-dihalogenation. For this purpose, thianthrenium dication is employed, and all possible combinations of chlorine and bromine are added onto internal alkenes successfully, particularly resulting in the syn-dibromination and the regiodivergent syn-bromochlorination.
Machine learning (ML) has quickly emerged in synthetic organic chemistry to predict reaction outcomes such as yields and stereoselectivities. Notably, recent applications of the ML approach showed ...powerful performance in solving various chemical problems. However, the requirement of numerous descriptors and large datasets hampers the general use by non‐specialists. In this study, simple ML models were developed by utilizing easily available 13C‐NMR chemical shifts of the substrates as familiar descriptors to predict the site‐selectivity of geminal chlorofluorination of unsymmetrical 1,2‐dicarbonyl compounds. We identified that the feed‐forward neural network (FNN) model provides higher accuracy compared to other algorithms. Then, better prediction performance was acquired through streamlined models using minimal, only empirically relevant descriptors.
We have evaluated the clinical outcomes of patients after transarterial chemoembolization (TACE) and 3-dimensional conformal radiotherapy for hepatocellular carcinoma (HCC) with portal vein tumor ...thrombosis (PVTT).
A registry database of 412 patients treated with TACE and three-dimensional conformal radiotherapy for HCC with PVTT between August 2002 and August 2008 were analyzed retrospectively. The radiotherapy volume included the PVTT, with a 2- to 3-cm margin to cover adjacent HCC. Intrahepatic primary HCC was managed by TACE before or after radiotherapy.
Median patient age was 52 years old, and 88.1% of patients were male. Main or bilateral PVTT was observed in 200 (48.5%) patients. Median radiation dose was 40 Gy (range, 21-60 Gy) delivered in 2- to 5-Gy fractions. We found that 3.6% of patients achieved a complete response and that 24.3% of patients achieved a partial response. The response and progression-free rates of PVTT were 39.6% and 85.6%, respectively. Median patient survival was 10.6 months, and the 1- and 2-year survival rates were 42.5% and 22.8%, respectively. Significant independent variables associated with overall survival included advanced tumor stage, alpha-fetoprotein level, degree of PVTT, and response to radiotherapy. Forty-one patients (10.0%) showed grade 3-4 hepatic toxicity during or 3 months after completion of radiotherapy. Grades 2-3 gastroduodenal complications were observed in 15 patients (3.6%).
Radiotherapy is a safe and effective treatment for PVTT in patients with HCC. These results suggested that the combination of TACE and radiotherapy is a treatment option for relieving and/or stabilizing PVTT in patients with advanced HCC.
Coronavirus disease 2019 (COVID-19) is an emerging threat worldwide. This study aims to assess the serologic profiles and time kinetics of antibodies against severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) in patients with COVID-19 using two immunoassays.
A total of 97 samples serially collected from 17 patients with COVID-19 and 137 negative control samples were analyzed for IgM and IgG against SARS-CoV-2 using the AFIAS COVID-19 Ab (Boditech Med Inc., Chuncheon, Republic of Korea) and the EDI™ Novel Coronavirus COVID-19 ELISA Kit (Epitope Diagnostics, Inc., San Diego, CA).
With both assays, IgM and IgG rapidly increased after 7 days post symptom onset (PSO). IgM antibody levels reached a peak at 15-35 d PSO and gradually decreased. IgG levels gradually increased and remained at similar levels after 22-35 d. The diagnostic sensitivities of IgM/IgG for ≤14d PSO were 21.4%/35.7~57.1% and increased to 41.2~52.9%/88.2~94.1% at >14 d PSO with specificities of 98.5%/94.2% for AFIAS COVID-19 Ab and 100.0%/96.4% for EDI™ Novel Coronavirus COVID-19 ELISA Kit. Among 137 negative controls, 12 samples (8.8%) showed positive or indeterminate results.
The antibody kinetics against SARS-CoV-2 are similar to common findings of acute viral infectious diseases. Antibody testing is useful for ruling out SARS-CoV-2 infection after 14 d PSO, detecting past infection, and epidemiologic surveys.
Following the worldwide surge in mpox (monkeypox) in 2022, cases have persisted in Asia, including South Korea, and sexual contact is presumed as the predominant mode of transmission, with a ...discernible surge in prevalence among immunocompromised patients. Drugs such as tecovirimat can result in drug‐resistant mutations, presenting obstacles to treatment. This study aimed to ascertain the presence of tecovirimat‐related resistant mutations through genomic analysis of the monkeypox virus isolated from a reported case involving prolonged viral shedding in South Korea. Here, tecovirimat‐resistant mutations, previously identified in the B.1 clade, were observed in the B.1.3 clade, predominant in South Korea. These mutations exhibited diverse patterns across different samples from the same patient and reflected the varied distribution of viral subpopulations in different anatomical regions. The A290V and A288P mutant strains we isolated hold promise for elucidating these mechanisms, enabling a comprehensive analysis of viral pathogenesis, replication strategies, and host interactions. Our findings imply that acquired drug‐resistant mutations, may present a challenge to individual patient treatment. Moreover, they have the potential to give rise to transmitted drug‐resistant mutations, thereby imposing a burden on the public health system. Consequently, the meticulous genomic surveillance among immunocompromised patients, conducted in this research, assumes paramount importance.
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