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Drug-lead synthesis through rapid construction of chiral molecular complexity around the biologically relevant framework using a highly efficient strategy is a key goal of organic synthesis. Molecules bearing a spirooxindole-type framework exhibit important bioactivities. Herein, we present a highly efficient and convenient strategy that allows rapid construction of unique optically active spiro[oxazoline-3,3'-oxindole]s through the organocatalyzed asymmetric synthesis of spirocyclic thiocarbamates via an aldol reaction. Preliminary biological evaluation of several of the spirooxazolines using a model of acute neuroinflammation revealed promising antipyretic activity and provided an opportunity to discover new antipyretic agents.

Due to the lack of tumor-specific anticancer agents, the discovery and development of new types of highly selective anticancer agents is still a very urgent topic. Herein, we present our contribution to concise construction of novel chiral spirooxindole-type pyranopyrimidines exhibiting a unique profile of biological activities. We have found that this new type of spiro alkaloid could inhibit the pro-liferation of various cancer cells in a preliminary biological evaluation. These findings suggested that spirooxindole-type pyranopyrimidines, developed by an asymmetric Michael/cyclization strategy, can potentially serve as a new kind of anticancer candidate.

A‐spiro‐ing: The title reaction of α‐isothiocyanato imides and methyleneindolinones has been realized for the first time using 1 as the catalyst. This newly developed synthetic method provides a simple, efficient, and environmentally friendly way to access, in an enantioselective manner, densely functionalized spirooxindoles having three contiguous stereogenic centers.

Chronic nonalcoholic steatohepatitis (NASH) is a metabolic disorder that often leads to liver fibrosis, a condition with limited therapy options. Adiponectin is an adipocytokine that regulates glucose and lipid metabolism via binding to its receptors AdipoR1 and AdipoR2, and AdipoRs signaling is reported to enhance fatty acid oxidation and glucose uptake. Here, we synthesize and report an adiponectin-based agonist JT003, which potently improves insulin resistance in high fat diet induced NASH mice and suppresses hepatic stellate cells (HSCs) activation in CCl4 induced liver fibrosis. Mechanistic studies indicate that JT003 simultaneously stimulates AdipoR1- and AdipoR2- mediated signaling pathways as well as the PI3K-Akt pathway. Moreover, JT003 treatment significantly improves ER-mitochondrial axis function, which contributes to the reduced HSCs activation. Thus, the AdipoR1/AdipoR2 dual agonist improves both NASH and fibrosis in mice models, which provides the pharmacological and biological foundation for developing AdipoRs-based therapeutic agents on liver fibrosis.

A novel and efficient Cu(OAc)2-catalyzed oxyazidation of unactivated alkenes was developed. The reactions are easy to conduct, occur under mild conditions, and form azido-substituted isoxazolines in good yields.

The first asymmetric decarboxylative [4 + 3] annulation of propargylic carbamates with C,N-cyclic azomethine imines has been developed successfully by a copper−N-heterocyclic carbine system. This strategy led to a series of optically active isoquinoline-fused triazepine derivatives in good yields and with excellent enantio-and diastereoselectivities. Remarkably, Cu−allenylidene intermediates play a crucial role in this transformation.

Abstract:The doubly stereocontrolled organocatalytic aza-Henry reaction of nitroalkanes to N-Bocimines generated in situ from a variety of substituted a-amido sulfones was investigated for the first time, in general, affording the corresponding products with high to excellent yields (up to 93% yield) and enantioselectivities (up to 98% ee), and satisfactory diastereoselectivies (anti/syn up to 98:2). Furthermore, these organocatalysts based on rosin have been proved to be the very effective promoters for this catalytic asymmetric process along side the Cinchona alkaloid-derived catalysts.Keywords: a-amido sulfones; asymmetric synthesis; aza-Henry reaction; imines; rosin-derived thioureaThe catalytic asymmetric aza-Henry reaction [1] constitutes one of the most versatile and attractive approaches for accessing optically active chiral b-nitro-A C H T U N G T R E N N U N G amines, which can be readily converted into valuable synthetic building blocks or biologically active vicinal diamines [2] and a-amino carbonyl compounds, [3] and could effectively be obtained by only two asymmetric catalytic ways to date (a: starting from N-protected imines; b: starting from a-amido sulfones, Scheme 1). Since Shibasaki reported the first catalytic asymmetric aza-Henry reaction of nitromethane to N-protected imines, [4] impressive progress has been made on the development of more selective and efficient catalytic systems involving metallic [5] and organic [6] catalysts for this asymmetric version. However, the preparation of these imines, such as N-carbamoylimines requires harsh conditions and their purification and storage are rather troublesome because of their inherent instability. To the best of our knowledge, only the two groups of Palomo [7a] and Ricci [7b] have independently reported catalytic asymmetric aza-Henry reactions with in situ generation of carbamate-protected imines from a-amido sulfones using the same chiral quaternary ammonium salt catalyst based on a Cinchona alkaloid by phase-transfer catalysis (PTC). Nevertheless, this more convenient and useful catalytic version remains a much less developed field and a practical asymmetric aza-Henry reaction with in situ generation of carbamate-protected imines catalyzed by other catalysts based on new chiral scaffolds has not yet been reported. Furthermore, except for a recently reported example, [8] Cinchona alkaloid derivatives were employed as exclusive efficient catalysts in all of the related asymmetric Mannich reactions with in situ generation of carbamate-protected imines from a-amido sulfones. [9] We recently reported [10] a new class of thiourea-derived bifunctional catalysts [11,12] based on rosin, which have successfully been applied to the doubly stereocontrolled synthesis of g-nitro heteroaromatic ketones. Herein, we describe our contribution to the progress of the catalytic asymmetric aza-Henry reaction and report the first doubly stereocontrolled Scheme 1. Two asymmetric catalytic ways.