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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

As one of the most aggressive and lethal human malignancies with extremely poor prognosis, there is an urgent demand of more effective therapy for the treatment of pancreatic cancer. Reported here is a new, effective therapeutic strategy and the design of small‐molecule inhibitors that simultaneously target bromodomain and extra‐terminal (BET) and histone deacetylase (HDAC), potentially serving as promising therapeutic agents for pancreatic cancer. A highly potent dual inhibitor (13 a) is identified to possess excellent and balanced activities against BRD4 BD1 (IC50=11 nm) and HDAC1 (IC50=21 nm). Notably, this compound shows higher in vitro and in vivo antitumor potency than the BET inhibitor (+)‐JQ1 and the HDAC inhibitor vorinostat, either alone or and in combination, highlighting the advantages of BET/HDAC dual inhibitors for more effective treatment of pancreatic cancer.

A simple formylation reaction of aryl halides, aryl triflates, and vinyl bromides under synergistic nickel- and organic-dye-mediated photoredox catalysis is reported. Distinct from widely used palladium-catalyzed formylation processes, this reaction proceeds by a two-step mechanistic sequence involving initial in situ generation of the diethoxymethyl radical from diethoxyacetic acid by a 4CzIPN-mediated photoredox reaction. The formyl-radical equivalent then undergoes nickel-catalyzed substitution reactions with aryl halides and triflates and vinyl bromides to form the corresponding aldehyde products. Significantly, besides aryl bromides, less reactive aryl chlorides and triflates and vinyl halides serve as effective substrates for this process. Since the mild conditions involved in this reaction tolerate a plethora of functional groups, the process can be applied to the efficient preparation of diverse aromatic aldehydes.