ortho-Alkynyl Benzyl Alcohols as C6 Synthons in Regioselective Construction of Polysubstituted Naphthalenes.

A straightforward methodology for the assembly of polysubstituted naphthalenes from ortho-alkynyl benzyl alcohols, enabled by using catalytic amounts of Tf2O, has been developed. This transformation not only features transition-metal free and without using other bases and additives but also provides a new synthetic application for ortho-alkynyl benzyl alcohols, i.e., as C6 synthons for the construction of PAHs.

Therapeutic potential of targeting kynurenine pathway in neurodegenerative diseases.

Kynurenine pathway (KP), the primary pathway of L-tryptophan (Trp) metabolism in mammals, contains several neuroactive metabolites such as kynurenic acid (KA) and quinolinic acid (QA). Its imbalance involved in aging and neurodegenerative diseases (NDs) has attracted much interest in therapeutically targeting KP enzymes and KP metabolite-associated receptors, especially kynurenine monooxygenase (KMO). Currently, many agents have been discovered with significant improvement in animal models but only one aryl hydrocarbon receptor (AHR) agonist 30 (laquinimod) has entered clinical trials for treating Huntington's disease (HD). In this review, we describe neuroactive KP metabolites, discuss the dysregulation of KP in aging and NDs and summarize the development of KP regulators in preclinical and clinical studies, offering an outlook of targeting KP for NDs treatment in future.

Targeting phosphodiesterase 4 as a therapeutic strategy for cognitive improvement.

Phosphodiesterase 4 (PDE4), the largest member of PDE family, is highly expressed in mammalian brain. It selectively hydrolyzes the second messenger cyclic adenosine monophosphate (cAMP), a correlate of brain functions including learning, memory and cognitive abilities. Its inhibition is beneficial to counteract cognitive deficits. Thus, targeting PDE4 may be a viable strategy for cognitive improvement. Currently, many PDE4 inhibitors have been discovered but with a great hurdle in clinical development due to adverse effects such as emesis. Analysis of PDE4 subtypes and discovery of subtype specific regulators indicate therapeutic benefits with improved safety in preclinical and clinical models. Herein, we summarize PDE4 structure, describe PDE4 mediated signaling pathways, review the role of individual PDE4 subtypes and discuss the development of PDE4 inhibitors for cognitive improvement, trying to give an insight into the strategy for cognitive improvement with PDE4 inhibitors in future.

Photocatalytic Remote Oxyfluoroalkylation of Heteroalkynes: Regio-, Stereo-, and Site-Selective Access to Complex Fluoroalkylated (Z)-Alkenes.

A visible-light-induced remote oxyfluoroalkylation, including ketofluoroalkylation and hydroxytrifluoromethylation, of heteroalkynes is developed with dimethyl sulfoxide (DMSO) and H2O as the oxygen source, respectively. It provides a facile access to complex fluoroalkylated (Z)-alkenes in satisfactory yields with excellent regio-, stereo-, and site-selectivity. The reaction involves an uncommon vinyl radical-induced intermolecular C(sp3)-H functionalization, thus offering a good platform for the development of remote difunctionalization of alkynes.

Photocatalytic 1,1-Hydrofluoroalkylation of Alkynes with a Concurrent Vicinal Acylation: An Access to Fluoroalkylated Cyclic Ketones.

A visible-light-induced 1,1-hydrofluoroalkylation of alkynes with a concomitant vicinal acylation is developed using tetrahydrofuran (THF) as the hydrogen atom source. Various fluoroalkylated cyclic ketones, such as indanones, chroman-4-ones, 2,3-dihydroquinolin-4(1 H)-ones, and 3,4-dihydronaphthalen-1(2 H)-ones, can be efficiently synthesized with excellent trans-diastereoselectivity. The reaction represents the first example of 1,1-hydrofluoroalkylation of alkynes, thus providing a novel method for the construction of fluoroalkanes.