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The concise total syntheses of oxidized norcembranoid terpenoids (-)-scabrolide A and (-)-yonarolide have been accomplished in 10 and 11 steps, respectively. The carbocyclic skeleton was efficiently constructed from two chiral-pool-derived fragments, including a [5,5]-bicyclic lactone accessed through a powerful Ni-catalyzed pentannulation of functionalized cyclopentenone with methylenecyclopropane and subsequent fragmentation. Additional features included a Liebeskind-Srogl coupling, induction of a cyclization/elimination cascade by a zinc-amido base, and installation of a sensitive enedione motif by late-stage γ-oxidation.

Alkaloids isolated from members of the Amaryllidaceae plant family are promising anticancer agents. The purpose of the current study was to determine if the isocarbostyrils narciclasine, pancratistatin, lycorane, lycorine, crinane, and haemanthamine inhibit phenomena related to cancer progression in vitro. To achieve this, we examined the proliferation, adhesion, and invasion of cultured human colon cancer cells via MTT assay and Matrigel-coated Boyden chambers. In addition, Luminex assays were used to quantify the secretion of matrix metalloproteinases (MMP) and cytokines associated with poor clinical outcomes. We found that all alkaloids decreased cell proliferation regardless of TP53 status, with narciclasine exhibiting the greatest potency. The effects on cell proliferation also appear to be specific to cancer cells. Narciclasine, lycorine, and haemanthamine decrease both adhesion and invasion but with various potencies depending on the cell line. In addition, narciclasine, lycorine, and haemanthamine decreased the secretion of MMP-1, -2, and -7, as well as the secretion of the cytokines pentraxin 3 and vascular endothelial growth factor. In conclusion, the present study shows that Amaryllidaceae alkaloids decrease phenomena and cytokines associated with colorectal cancer progression, supporting future investigations regarding their potential as multifaceted drug candidates.

The use of sodium dithionite with perfluoroalkyl iodides under basic conditions facilitates the direct perfluoroalkylation of arenes with pendant benzylic electron-withdrawing groups. This occurs via attack of the arene on the electrophilic perfluoroalkyl radical, through the donation of electron density from a benzylic anion. The substrate scope was expanded beyond benzylic nitriles with cyclic substrates bearing electron-withdrawing groups at the benzylic position-enforcing donation of electron density to the aromatic ring and enabling attack on the perfluoroalkyl radical.

Chiral phosphoric-acid-catalyzed asymmetric reductions of trans -chalcones have been investigated in this work. A BINOL-derived boro-phosphate-catalyzed asymmetric transfer hydrogenation of the carbon-carbon double bond of trans -chalcone derivatives employing borane as a hydride source was realized. This methodology provides a convenient procedure to access chiral dihydrochalone derivatives in high yields and with high enantioselectivities under mild conditions.

Synthesis of natural products remains a daring task. Their richly diverse and intricate structures often encompass a large degree of unsaturation, contain fused and/or bridged rings, or possess numerous stereogenic centers. Thus, their preparation requires significant synthetic overhead, detracting from their overall practicality as well as hampering the ability of medicinal chemists to synthesize derivatives for pharmaceutical optimization and structure-activity relationship studies. The purpose of this Minireview is to showcase recent examples of efficient total syntheses. Emphasis was not given to the evaluation of ideality or economies (quality), but rather to the practicality (quality with quantity)., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Enantioselective total syntheses of the anticancer isocarbostyril alkaloids (+)-7-deoxypancratistatin, (+)-pancratistatin, (+)-lycoricidine, and (+)-narciclasine are described. Our strategy for accessing this unique class of natural products is based on the development of a Ni-catalyzed dearomative trans-1,2-carboamination of benzene. The effectiveness of this dearomatization approach is notable, as only two additional olefin functionalizations are needed to construct the fully decorated aminocyclitol cores of these alkaloids. Installation of the lactam ring has been achieved through several pathways and a direct interconversion between natural products was established via a late-stage C-7 cupration. Using this synthetic blueprint, we were able to produce natural products on a gram scale and provide tailored analogs with improved activity, solubility, and metabolic stability.

We describe the development of an arenophile-mediated, nickel-catalyzed dearomative trans-1,2-carboamination protocol. A range of readily available aromatic compounds was converted to the corresponding dienes using Grignard reagents as nucleophiles. This strategy provided products with exclusive trans-selectivity and high enantioselectivity was observed in case of benzene and naphthalene. The utility of this methodology was showcased by controlled and stereoselective preparation of small, functionalized molecules.

A concise synthesis of (+)-pancratistatin and (+)-7-deoxypancratistatin from benzene using an enantioselective, dearomative carboamination strategy has been achieved. This approach, in combination with the judicious choice of subsequent olefin-type difunctionalization reactions, permits rapid and controlled access to a hexasubstituted core. Finally, minimal use of intermediary steps as well as direct, late stage C-7 hydroxylation provides both natural products in six and seven operations.

Intellectual disability (ID) is a prevalent form of non-progressive cognitive impairment. The objectives of this articles are: to analyze the changes of ID in China, including its definition, prevalence, rehabilitation, education, vocational development, social life and support services; to review and to compare the issues of intellectual disability in China with the international literatures and research studies and to provide useful updated information and reference data for scholars and researchers who study intellectual disability. Analyzed the data obtained from two national sample surveys on disability with respect to intellectual disability in China. The estimated prevalence of individuals with intellectual disabilities in China was 7.5‰ in 2006 nationally which was lower than the previous results obtained in the 1987 national survey. The fourth level of ID showed a downward trend, while the proportion among the population aged 60 and over with ID tended to increase. The 2006 national survey indicated that the prevalence of ID in rural areas was higher than that in urban areas. This finding was consistent with the national survey conducted in 1987. As indicated by the 2006 national survey, 29.4% cases had no known causes for the ID, the proportion tended to decrease as compared with the first survey. However, when compared to the 1987 report, the proportion of senile dementia among older people as indicated by the 2006 report was higher than before. During the past years, the prevention of ID and the quality of life of individuals with ID have improved due to the enactment and implementation of a series of national laws and regulations, however, there is more that needs to be done in the areas of education, vocational development, social integration and support services for individuals with ID in order to improve the quality of life of individuals with ID in China. The findings of this study are consistent with the research findings presented in the international literatures. ID is the conditions that deserve further study and deserve the attention of policy makers and rehabilitation professionals in China. Furthermore, with the ageing of population in China and its impact to the social security system, the in-depth study of ID and its implications has become more pertinent in China in the future., (Copyright © 2010 Elsevier Ltd. All rights reserved.)