Migraine is a neurological disorder characterized by severe headaches, visual aversions, auditory, and olfactory disorders, accompanied by nausea and vomiting. Zolmitriptan (ZMT) is a potent 5HT1B/1D serotonin receptor agonist frequently used for the treatment of migraine. It has erratic absorption from the gastrointestinal tract (GIT), but its oral bioavailability is low (40-45%) due to the hepatic metabolism.
View Article and Find Full Text PDFBrain metastases present mostly multifocal, infiltrative and co-opting growth with the blood-brain barrier (BBB) remaining intact. The BBB, as the barrier of drug delivery to such lesions, is the major cause of the failure of systemic drug therapy and needs to be conquered. Angiopep-2 ligates the low density lipoprotein receptor related protein 1 (LRP1) on brain microvascular endothelial cells (BMECs) to drive transcytosis for BBB crossing.
View Article and Find Full Text PDFThe first catalytic enantioselective construction of biologically important tetrahydroquinolin-5-one-based spirooxindole has been developed via a chiral cinchona alkaloid catalyzed asymmetric three-component [3 + 3] cyclization of cyclic enaminone, isatin, and malononitrile, which afforded a series of tetrahydroquinolin-5-one-based spirooxindoles in high yields and with excellent enantioselectivities (up to 99% yield, 97:3 er). This reaction could be applicable to large-scale synthesis of enantioenriched tetrahydroquinolin-5-one-based spirooxindoles. This synthetic methodology will not only provide a unique approach for the construction of chiral tetrahydroquinolin-5-one-based spirooxindole scaffolds but also increase our understanding of catalytic enantioselective multicomponent reactions.
View Article and Find Full Text PDFThe first catalytic asymmetric construction of the biologically important hexahydrocoumarin scaffold has been established, which takes advantage of chiral thiourea-tertiary amine-catalyzed enantioselective transformations. Besides, this reaction also realized the first catalytic asymmetric [3 + 3] cyclization of 4-arylidene-2-aryloxazol-5(4H)-ones with cyclohexane-1,3-diones, which afforded structurally diverse 3-aminohexahydrocoumarin derivatives in excellent diastereoselectivities and high enantioselectivities (all >95:5 dr, up to 96:4 er). The investigation on the activation mode suggested that the chiral thiourea-tertiary amine catalyst simultaneously activated the two substrates via hydrogen-bonding interaction.
View Article and Find Full Text PDFAn enantioselective [4 + 2] cycloaddition of o-hydroxylstyrenes with azlactones has been established by merging chiral Brønsted acid (chiral phosphoric acid) and base (chiral guanidine) catalysis, which constructed a biologically important dihydrocoumarin scaffold in an efficient and enantioselective style (up to 99% yield, 96:4 er). This approach has not only realized the successful application of o-hydroxylstyrenes as oxa-diene precursors in catalytic asymmetric cycloadditions but also established a new cooperative catalytic system of chiral phosphoric acid and chiral guanidine.
View Article and Find Full Text PDFA chiral phosphoric acid-catalyzed asymmetric reaction of 2-indolylmethanols with 3-alkylindoles has been established, which constructed a biologically important 2,2'-bisindolylmethane scaffold in high yields and good enantioselectivities (up to 98% yield, 94:6 er). This protocol not only provides an efficient method for constructing a 2,2'-bisindolylmethane framework in an enantioselective form, but also promotes the development of 2-indolylmethanol-involved catalytic asymmetric transformations.
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