Catalytic enantioselective conjugate addition of grignard reagents to cyclic enones using C 1 -1,1′-bisisoquinoline-based chiral ligands

New highly constrained chiral C1-1,10-bisisoquinoline ligands were examined in the enantioselective conjugate addition of Grignard reagents to cyclohexenone and cyclopentenone. The desired 1,4-adducts were obtained in excellent yield and moderate enantiomeric excess (up to 35%)

Efficient, one-step, cascade synthesis of densely functionalized furans from unprotected carbohydrates in basic aqueous media

Condensation of unprotected carbohydrates with malononitrile or malonamide nitrile in basic aqueous media gave in one-pot densely functionalized polyhydroxyalkyl 2-amino-3-furanonitriles and polyhydroxyalkyl 2-amino-3-furanocarboxamides in excellent 84–98% yields. Disaccharides afforded novel furano-glycosides. Based on the rate of formation of the furans, the ability of the tested bases to catalyze the reaction was concluded as Et₃N > DBU > K₂CO₃ > NaOMe. The reaction mechanism involved the formation of bicyclic furan-furan and furan-pyran intermediates observed for the first time. The reaction proceeded through a cascade mechanism involving Knoevenagel condensation, Oxo-Micheal addition, Thorpe-Ziegler type reaction and ring-opening-induced aromatization. This operationally simple and metal-free reaction proceeded with exclusive chemo-, regio-, and stereo-selectivities under environmentally benign conditions. As demonstrated on a 2 g scale, it holds promise for application in the large-scale synthesis of important intermediates such as densely functionalized furfural.Nanyang Technological UniversityWe thank Nanyang Technological University, Singapore for financial help (RG 142/16)

Short synthesis of phenylpropanoid glycosides calceolarioside A and syringalide B

An efficient and practical three-step synthesis of phenylpropanoid glycosides calceolarioside A and syringalide B in >62% overall yield is disclosed. The key step involves the chemoselective and regio selective direct O-4 cinnamoylation of unprotected 2-phenylethyl-β-d-glucosides with cinnamic anhydrides using a chiral 4-pyrrolidinopyridine organocatalyst. This approach serves as a model for the short synthesis of phenylpropanoid glycosides acylated at O-4 without protection/deprotection steps

Selective one-pot multicomponent synthesis of N-substituted 2,3,5-functionalized 3-cyanopyrroles via the reaction between α-hydroxyketones, oxoacetonitriles, and primary amines

A one-step, three-component reaction between α-hydroxyketones, oxoacetonitriles, and primary amines gives N-substituted 2,3,5-functionalized 3-cyanopyrroles with complete selectivity in up to 90% isolated yields. The reaction worked on a wide substrate scope under mild reaction conditions (AcOH as a catalyst, EtOH, 70 °C, 3 h). The reaction proceeded with very high atom efficiency as water is the only molecule lost during the reaction. The practicality of the reaction was demonstrated on a large gram scale. The structures of the 3-cyanopyrroles were confirmed by single-crystal X-ray diffraction and NMR; this work provides a general and practical entry to pyrrole scaffolds suitably decorated for the synthesis of various bioactive pyrroles in a concise manner.Nanyang Technological UniversityPublished versionThis research was funded by the College of Engineering (Startup Grant), Nanyang Technological University, Singapore and by United Arab Emirates University (UAEU), Al-Ain (Grant no. G00003291/Fund no. 31S401/12S040/Project #852)

Acetic acid-catalyzed selective synthesis of N-substituted 2-amino-3-cyanopyrroles via a three-component reaction between carbohydrates, primary amines and malononitrile

Direct conversion of unprotected carbohydrates to N-heterocycles is challenging and highly desirable. A simple three-component synthesis of N-substituted 2-amino-3-cyanopyrrole key framework is developed from the reaction between unprotected carbohydrates, malononitrile, and primary amines. The reaction proceeded under mild reaction conditions (AcOH catalyst, EtOH, 60 °C, 2 hours), tolerated a wide substrate scope, worked smoothly on a 4 g scale, and gave the pyrroles in up to 86% yield. The pyrroles were also converted into functional intermediates to demonstrate their versatility. NMR and LC–MS experiments supported a proposed cascade reaction mechanism. The approach demonstrates a robust upcycling process for the challenging synthesis of highly functionalized N-heterocyclic compounds from unprotected carbohydrates.Nanyang Technological UniversityWe thank Nanyang Technological University, Singapore, for the start-up grant

A concise synthesis of pyrrole-based drug candidates from α-hydroxyketones, 3-oxobutanenitrile, and anilines

A simple and concise three-component synthesis of a key pyrrole framework was developed from the reaction between α-hydroxyketones, oxoacetonitriles, and anilines. The synthesis was used to obtain several pyrrole-based drug candidates, including COX-2 selective NSAID, antituberculosis lead candidates BM212, BM521, and BM533, as well as several analogues. This route has potential to obtain diverse libraries of these pyrrole candidates in a concise manner to develop optimum lead compounds.Nanyang Technological UniversityPublished versionThis research was funded by the College of Engineering (Startup Grant), Nanyang Technological University, Singapore, and by the United Arab Emirates University (UAEU), Al-Ain (Grant no.G00003918)

Fabrication of quercetin nanoparticles by anti-solvent precipitation method for enhanced dissolution

The aim of this study was to enhance the dissolution rate of a poorly water-soluble drug quercetin by fabricating its nanoparticles with anti-solvent precipitation using the syringe pump and to investigate the effect of drug concentration, solvent to anti-solvent (S/AS) ratio, stirring speed and flow rate on the particle size. Characterization of the original quercetin powder and nanoparticles made by syringe pump was carried out by the scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and dissolution tester. The results indicated that decreasing the drug concentration, increasing the stirring speed, flow rate and the S/AS volume ratio favoured the reduction in the particle diameter to ∼ 170 nm. Percent dissolution efficiency (%DE); relative dissolution (RD); mean dissolution time (MDT); difference factor (f1) and similarity factor (f2) were calculated for the statistical analysis. The dissolution of the drug nanoparticles was significantly higher compared with the pure drug in simulated intestinal fluid (SIF, pH 6.8)

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides

A convenient protocol was developed for the synthesis of 2,3-unsaturated C-, O-, N- and S-linked glycosides (enosides) using 20 mol % perflurophenylboronic acid catalyst via Ferrier rearrangement. Using this protocol, D-glucals and L-rhamnals reacted with various C-, O-, N- and S-nucleophiles to give a wide range of glycosides in up to 98% yields with mainly α-anomeric selectivity. The perflurophenylboronic acid successfully catalyzed a wide range of substrates (both glucals and nucleophiles) under very mild reaction conditions.Published versio