Oxidation of Primary Alcohols and Aldehydes to Carboxylic Acids with 1-Hydroxycyclohexyl Phenyl Ketone.

The oxidation of primary alcohols to the corresponding carboxylic acids is one of the fundamental and useful reactions in organic synthesis. In this paper, we report our comprehensive results toward the oxidation of primary alcohols and aldehydes to acids via hydride transfer reactions mediated by 1-hydroxycyclohexyl phenyl ketone. Under the strong basic conditions of sodium tert-butoxide, the room temperature oxidations tolerate a range of functional groups, including vulnerable tert-butanesulfinamides, amines, sulfides, olefins, and heterocycles, and provide good to excellent yields. Most importantly, our oxidation procedure can be applied to chemoselective oxidation of primary alcohols and aldehydes to carboxylic acids in the presence of secondary alcohols.

Total Synthesis of (-)-Vindorosine.

Outlined herein is a novel and scalable synthesis of (-)-vindorosine based on two key transformations. A highly diastereoselective vinylogous Mannich addition of dioxinone-derived lithium dienolates with indolyl N-tert-butanesulfinyl imines has been developed. In addition, an intramolecular Heathcock/aza-Prins cyclization was introduced to construct both the C, and the highly substituted E rings for the synthesis of (-)-vindorosine and related alkaloids.

miR-99a-5p: A Potential New Therapy for Atherosclerosis by Targeting mTOR and Then Inhibiting NLRP3 Inflammasome Activation and Promoting Macrophage Autophagy.

Objective: MicroRNAs have been revealed to be involved in the development of atherosclerosis. The present study is aimed at exploring the potential of miR-99a-5p as a therapy for atherosclerosis. We suspected that miR-99a-5p might inhibit NLRP3 inflammasome activation and promote macrophage autophagy via constraining mTOR, therefore, alleviating atherosclerosis. Methods: The cell viability in ox-LDL-induced THP-1 macrophages was assessed by CCK-8 assay. Bioinformatic analysis was used to predict the target genes of miR-99a-5p. The binding between miR-99a-5p and mTOR was confirmed by luciferase reporter assay. In vivo, a high-fat-diet-induced atherosclerosis model was established in apolipoprotein E knockout mice. Hematoxylin-eosin, oil red O, and Sirius red staining were performed for the determination of atherosclerotic lesions. MTOR and associated protein levels were detected by Western blot analysis. Results: miR-99a-5p inhibited NLRP3 inflammasome activation and promoted macrophage autophagy by targeting mTOR. Enforced miR-99a-5p significantly reduced the levels of inflammasome complex and inflammatory cytokines. Furthermore, miR-99a-5p overexpression inhibited the expression of mTOR, whereas mTOR overexpression reversed the trend of the above behaviors. In vivo, the specific overexpression of miR-99a-5p significantly reduced atherosclerotic lesions, accompanied by a significant downregulation of autophagy marker CD68 protein expression. Conclusion: We demonstrated for the first time that miR-99a-5p may be considered a therapy for atherosclerosis. The present study has revealed that miR-99a-5p might inhibit NLRP3 inflammasome activation and promote macrophage autophagy by targeting mTOR, therefore, alleviating atherosclerosis.

Oxidation of Primary Alcohols and Aldehydes to Carboxylic Acids via Hydrogen Atom Transfer.

The oxidation of primary alcohols and aldehydes to the corresponding carboxylic acids is a fundamental reaction in organic synthesis. In this paper, we report a new chemoselective process for the oxidation of primary alcohols and aldehydes. This metal-free reaction features a new oxidant, an easy to handle procedure, high isolated yields, and good to excellent functional group tolerance even in the presence of vulnerable secondary alcohols and tert-butanesulfinamides.