Kezhou Wang

MgII‐Mediated Catalytic Asymmetric Dearomatization (CADA) Reaction of β‐Naphthols with Dialkyl Acetylenedicarboxylates

A Mg(II) -mediated catalytic asymmetric dearomatization (CADA) reaction of β-naphthols has been developed. The reaction proceeds under ambient temperature and give a series of chiral trisubstituted olefins with good chemoselectivities, Z/E ratios, and excellent enantioselectivities. A fluorinated β-naphthol was designed to generate chiral organofluorine skeletons through the current CADA reaction. Moreover, an interesting tandem cyclization reaction was observed in the following transformation process through an undiscovered intramolecular hydride transfer pathway.

Nickel-Mediated Asymmetric Allylic Alkylation between Nitroallylic Acetates and Acyl Imidazoles

A nickel-mediated asymmetric allylic alkylation reaction between imidazole-modified ketones and nitroallylic acetates is presented. This reaction is catalyzed by a simple chiral diamine-nickel catalyst under mild conditions and leads to a series of novel enantioenriched α-allylic adducts in moderate to good yields with excellent enantioselectivities. Furthermore, transformation of the allylic adducts could smoothly lead to chiral γ-nitro-esters containing three continuous stereocenters in good yields.

Development of Biligands Magnesium Catalysis in Asymmetric Conjugate Reactions of C3-Pyrrolyl-Oxindoles

A magnesium catalyzed asymmetric conjugate reaction of C3-pyrrolyl-oxindoles with terminal alkynones is presented. The current asymmetric conjugate reaction relies on the development of novel combinational magnesium catalysis involving two chiral ligands. The current protocol proceeds smoothly and gives the corresponding enantioenriched 3,3-disubstituted oxindole skeletons with good enantioselectivities. Furthermore, the conjugate adducts could be transferred to spiro oxindole structures containing an eight-membered ring in high ee values.

Magnesium Catalysis Mediated Tetrazoles in Desymmetrization Reaction of Aziridines

A magnesium-catalyzed asymmetric ring-opening reaction of aziridines with substituted tetrazoles is reported. The current protocol proceeds smoothly and gives the corresponding desymmetrization products in high yields and good enantioselectivities. A new chiral ligand was synthesized from azetidine and (R)-BINOL and was employed in the current in situ generated magnesium catalyst. The Mg(II)-mediated desymmetrization reaction could be performed on gram scale under mild conditions and was transformed to chiral alkyl amines by a deprotection process.

An Efficient Nickel-Catalyzed Asymmetric Oxazole-Forming Ugi-Type Reaction for the Synthesis of Chiral Aryl-Substituted THIQ Rings

A nickel-catalyzed asymmetric oxazole-forming Ugi reaction of C,N-cyclic azomethine imines and isonitriles is disclosed. The reported protocol proceeds smoothly, and gives the corresponding adducts, which contain two important pharmaceutically active ring-systems (tetrahydroquinoline and oxazole rings), in good yields and excellent enantioselectivities by employing an easily accessible chiral diamine as a ligand. This simple and efficient strategy provides easy access to a series of C1-substituted aryl tetrahydroisoquinolines.

The Important Role of the Byproduct Triphenylphosphine Oxide in the Magnesium(II)‐Catalyzed Enantioselective Reaction of Hemiacetals and Phosphorus Ylides

By employing a simple in situ generated magnesium catalyst, a direct asymmetric reaction between hemiacetals and phosphorus ylides was achieved through a tandem Wittig-oxa-Michael reaction sequence. Enantioenriched chromans, isochromans, and tetrahydropyrans were obtained in good chemical yields, and (-)-erythrococcamide B was synthesized in enantioenriched form. The byproduct triphenylphosphine oxide was identified as a necessary additive for this process.

Enantioselective Reaction between 2-(Cyanomethyl)azaarenes and N-Boc-amino Sulfones

A series of 2-(cyanomethyl)azaarenes containing benzothiazole or benzoxazole were designed and synthesized for asymmetric α-functionalization with N-Boc-amino sulfones. The Mannich adducts were obtained in high yields with good diastereo- and enantioselectivities. Aryl-substituted amino sulfones were tolerated under the current conditions, and the reaction can be performed on gram scale in good results.

Structure-constrained endomorphin analogs display differential antinociceptive mechanisms in mice after spinal administration

&NA; We previously reported a series of novel endomorphin analogs with unnatural amino acid modifications. These analogs display good binding affinity and functional activity toward the &mgr; opioid receptor (MOP). In the present study, we further investigated the spinal antinociceptive activity of these compounds. The analogs were potent in several nociceptive models. Opioid antagonists and antibodies against several endogenous opioid peptides were used to determine the mechanisms of action of these peptides. Intrathecal pretreatment with naloxone and &bgr;‐funaltrexamine (&bgr;‐FNA) effectively inhibited analog‐induced analgesia, demonstrating that activity of the analogs is regulated primarily through MOP. Antinociception induced by analog 2 through 4 was not reversed by &dgr; opioid receptor (DOP) or &kgr; opioid receptor (KOP) antagonist; antibodies against dynorphin‐A (1–17), dynorphin‐B (1–13), and Leu5/Met5‐enkephalin had no impact on the antinociceptive effects of these analogs. In contrast, antinociceptive effects induced by a spinal injection of the fluorine substituted analog 1 were significantly reversed by KOP antagonism. Furthermore, intrathecal pretreatment with antibodies against dynorphin‐B (1–13) attenuated the antinociceptive effect of analog 1. These results indicate that the antinociceptive activity exerted by intrathecally‐administered analog 1 is mediated, in part, through KOP with increased release of dynorphin‐B (1–13). The chemical modifications used in the present study may serve as a useful tool to gain insight into the mechanisms of endomorphins activity. Graphical abstract Figure. No caption available. HighlightsEM‐1 analogs showed better analgesic activity than their parent peptide after i.t. injection.Analog 1 increases release of dynorphin B (1–13) in spinal cord.Fluorinated modification of endomorphins may alter their mechanism of action.