An approach for efficient synthesis of Cglycosyl amino acids is described. Different from typical photoredox-catalyzed reactions of imines, the new process follows a pathway in which α-imino esters serve as electrophiles in chemoselective addition reactions with nucleophilic glycosyl radicals. The process is highlighted by the mild nature of the reaction conditions, the highly stereoselectivity attending C−C bond formation, and its applicability to C-glycosylations using both armed and disarmed pentose and hexose derivatives.C-Glycosyl amino acids are a unique class of compounds widely present in nature that have an enormously diverse array of biological properties. 1 Notable examples of substances in this family include the peptidyl nucleoside antibiotics amipurimycin, polyoxins, and nikkomycin, which have potent antimycotic activities against various human pathogenic fungi and bacteria (Scheme 1A). 2,3 More pronounced impacts of Cglycosyl amino acids arise from their broad application in biomedical and drug discovery studies of glycopeptides and proteins. 4,5 Finally, the presence of C−C linkages to anomeric centers gives members of this family higher metabolic stabilities and lipophilicities than those of O−C bondcontaining counterparts. In many instances, this feature leads to improved biological activities, membrane permeabilities, and bioavailabilities. 4,5 In routes developed to date for the synthesis of C-glycosyl amino acids, installation of an amino acid moiety onto a glycosyl framework has relied on the use of well-established αamino acid synthesis strategies, such as alkylation of α-amino acid equivalents, Strecker reactions, hydrogenation of dehydroamino acids, and multicomponent Ugi reactions with sugar derivatives (Scheme 1B). 6 In addition, de novo synthesis of Cglycosyl amino acids has been shown to be a viable approach to access unnatural substances in this family. Although often reliable, these polar bond disconnection based methods are inherently limited by a number of factors including the need for lengthy synthetic sequences, harsh reaction conditions, and/or a limited substrate scope. 7 As part of a recent program to develop radical-based crosscoupling processes for selective C−C bond formation, 8 we envisaged that an open-shell pathway might be applicable to the concise synthesis of C-glycosyl amino acids under mild conditions. 9,10 Specifically, we believed that addition of glycosyl radicals, generated from appropriate glycosyl pre-cursors, to readily available α-imino esters would constitute a viable approach to the preparation of these substances (Scheme 1C). To our knowledge, a strategy of this type has
A mild, versatile organophotoredox protocol has been developed for the preparation of diverse, enantioenriched α-deuterated α-amino acids. Distinct from the well-established two-electron transformations, this radical-based strategy offers the unrivaled capacity of the convergent unification of readily accessible feedstock carboxylic acids and a chiral methyleneoxazolidinone fragment and the simultaneous highly diastereo-, chemo-, and regioselective incorporation of deuterium. Furthermore, the approach has addressed the long-standing challenge of the installation of sterically demanding side chains into α-amino acids.
Because of the continuous stream of touchscreen apps that are claimed to be educational and the increasing use of touchscreen devices in early childhood, considerable attention is being paid to the effect of touchscreens on young children's learning. However, the existing empirical findings in young child samples are not consistent. In this meta-analysis we tested the overall effect of touchscreen devices on young children's (0- to 5-year-olds) learning performance, as well as moderators of this effect, based on 36 empirical articles (79 effect sizes) involving 4,206 participants. The overall analysis showed a significant touchscreen learning effect (d = 0.46), indicating that young children indeed benefited from touchscreen learning. Interestingly, age, learning material domain, comparison group, and experimental environment significantly moderated the effect of touchscreen devices on young children's learning outcome. These findings shed light on the role of touchscreen-related physical experience in early childhood education.
The oncogenic STAT3 signaling pathway is emerging as a promising target for the treatment of multiple myeloma (MM). In the present study, we identified a novel STAT3 inhibitor SC99 in a target-based high throughput screen. SC99 inhibited JAK2-STAT3 activation but had no effects on other transcription factors such as NF-κB, and kinases such as AKT, ERK, and c-Src that are in association with STAT3 signaling pathway. Furthermore, SC99 downregulated the expression of STAT3-modulated genes, including Bcl-2, Bcl-xL, VEGF, cyclin D2, and E2F-1. By inhibiting the STAT3 signaling, SC99 induced MM cell apoptosis which could be partly abolished by the ectopic expression of STAT3. Furthermore, SC99 displayed potent anti-MM activity in two independent MM xenograft models in nude mice. Oral administration of SC99 led to marked decrease of tumor growth within 10 days at a daily dosage of 30 mg/kg, but did not raise toxic effects. Taken together, this study identified a novel oral JAK2/STAT3 inhibitor that could be developed as an anti-myeloma agent.
Am etal-and oxidant-free catalytic methodf or accessing structurally diverse thioesters from readily accessible, widespread aldehydes, is described. As trategy of a simple organic9 ,10-phenanthrenequinone-promoted hydrogen atom transfer (HAT) with visible light was successfully implemented to selectively generate acyl radicals withouti nducing crossover reactivity of thioester products. The preparative power of the method was demonstrated by broad substrate scope and wide functional group tolerance, and enabled the late-stage modification of complex structures, which are difficult to achieve with the existing protocols.Scheme1.Metal-free thioesterificationo faldehydes. DMP:Dess-Martin periodinane;TEMPO: (2,2
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