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The photoredox electron donor–acceptor (EDA) complex‐mediated radical coupling reaction has gained prominence in the field of organic synthesis, finding widespread application in two‐component coupling reactions. However, EDA complex‐promoted multi‐component reactions are not well developed with only a limited number of examples have been reported. Herein, we report a photoinduced and EDA complex‐promoted highly chemoselective three‐component radical arylalkylation of [1.1.1]propellane, which allows the direct functionalization of C(sp3)−H with bicyclo[1.1.1]pentanes (BCP)‐aryl groups under mild conditions. A variety of unnatural α‐amino acids, featuring structurally diversified 1,3‐disubstituted BCP moieties, were synthesized in a single‐step process. Notably, leveraging the high tension release of [1.1.1]propellane, the highly unstable transient aryl radical undergoes rapid conversion into a relatively stable tertiary alkyl transient radical, and consequently, the competing side‐reaction of two‐component coupling was entirely suppressed. The strategic use of this transient radical conversion approach would be useful for the design of diverse EDA complex‐mediated multi‐component reactions. It is noteworthy that the highly chemoselective late‐stage incorporation of the 1,3‐disubstituted BCP pharmacophores into peptides was achieved both in liquid‐phase and solid‐phase reactions. This advancement is anticipated to have significant application potential in the future development of peptide drugs. [ABSTRACT FROM AUTHOR]

Ischemic heart disease (IHD) remains a major global health concern, with ischemia-reperfusion injury exacerbating myocardial damage despite therapeutic interventions. In this study, we investigated the role of tropomyosin 3 (TPM3) in protecting cardiomyocytes against hypoxia-induced injury and oxidative stress. Using the AC16 and H9c2 cell lines, we established a chemical hypoxia model by treating cells with cobalt chloride (CoCl2) to simulate low-oxygen conditions. We found that CoCl2 treatment significantly upregulated the expression of hypoxia-inducible factor 1 alpha (HIF-1α) in cardiomyocytes, indicating the successful induction of hypoxia. Subsequent morphological and biochemical analyses revealed that hypoxia altered cardiomyocyte morphology disrupted the cytoskeleton, and caused cellular damage, accompanied by increased lactate dehydrogenase (LDH) release and malondialdehyde (MDA) levels, and decreased superoxide dismutase (SOD) activity, indicative of oxidative stress. Lentivirus-mediated TPM3 overexpression attenuated hypoxia-induced morphological changes, cellular damage, and oxidative stress imbalance, while TPM3 knockdown exacerbated these effects. Furthermore, treatment with the HDAC1 inhibitor MGCD0103 partially reversed the exacerbation of hypoxia-induced injury caused by TPM3 knockdown. Protein–protein interaction (PPI) network and functional enrichment analysis suggested that TPM3 may modulate cardiac muscle development, contraction, and adrenergic signaling pathways. In conclusion, our findings highlight the therapeutic potential of TPM3 modulation in mitigating hypoxia-associated cardiac injury, suggesting a promising avenue for the treatment of ischemic heart disease and other hypoxia-related cardiac pathologies. [ABSTRACT FROM AUTHOR]

Alkylnitriles play important roles in many fields because of their unique electronic properties and structural characteristics. Incorporating cyanoalkyl with characteristic spectroscopy and reactivity properties into amino acids and peptides is of special interest for potential imaging and therapeutic purposes. Here, we report a copper-catalyzed asymmetric cyanoalkylation of C(sp3)-H. In the reactions, glycine derivatives can effectively couple with various cycloalkanone oxime esters with high enantioselectivities, and the reaction can be applied to the late-stage modification of peptides with good yields and excellent stereoselectivities, which is useful for modern peptide synthesis and drug discovery. The mechanistic studies show that the in situ formed copper complex by the coordination of glycine derivatives and chiral phosphine Cu catalyst can not only mediate the single electronic reduction of cycloalkanone oxime ester but also control the stereoselectivity of the cyanoalkylation reaction. Incorporating cyanoalkyl moieties into amino acids and peptides is of interest for potential imaging and therapeutic purposes. Here, the authors developed a Cu-catalyzed asymmetric cyanoalkylation of glycine derivatives for the synthesis of α-cyanoalkylate amino acids and peptide modification. [ABSTRACT FROM AUTHOR]

The glycosylative modification of peptides could improve the pharmacological properties of peptide drugs and deliver them efficiently to the target sites. Compared with O‐/N‐glycosides, C‐glycosides exhibit more metabolic stability. We here disclose the first example of visible‐light‐promoted and Cu‐catalyzed stereoselective C‐glycosylation. The mild reaction conditions are compatible with various carbohydrate substrates, as demonstrated with a series of monosaccharides and a disaccharide, and are amenable to the synthesis of a wide variety of C‐glycoamino acids and C‐glycopeptidomimetics with good yields and excellent stereoselectivities. The dual‐functional photocatalyst formed in situ via coordination of the glycine derivative and the chiral phosphine Cu complex could not only catalyze the photoredox process but also control the stereoselectivity of the glycosylation reaction. [ABSTRACT FROM AUTHOR]