An approach towards (+)-allokainic acid via diphenylprolinol-catalyzed direct cross-aldol reaction.

This article describes an enantioselective strategy for the synthesis of the kainoid component, (+)-allokainic acid using an organocatalytic approach. A cross-aldol reaction catalyzed by diphenylprolinol yielded a highly functionalized γ-lactam with excellent enantio- and diastereoselectivity, and the resulting hydroxy pyrrolidone was then utilized to synthesize Ganem's intermediate of (+)-allokainic acid. Krapcho decarboxylation and Wittig olefination were pivotal transformations towards the final trans-substituted Ganem's intermediate.

Synthetic access to syn-functionalised chiral hydroxy pyrrolidines and pyrrolidones: Evaluation of α-glucosidase inhibition activity, docking studies and pharmacokinetics prediction.

A new series of syn-functionalised chiral hydroxy pyrrolidines and pyrrolidones containing α,ß-contiguous stereocenters were synthesized via a diphenylprolinol-catalysed asymmetric cross aldol reaction. The synthesized compounds were characterised and evaluated for their α-glucosidase inhibitory potential. The hydroxy pyrrolidine series (9a-9i) was found to be selectively more potent against the α-glucosidase enzyme as compared to the pyrrolidone series (10a-10i). Pyrrolidine 9b was the most efficacious analogue with an IC50 of 48.31 µM. Compounds 9c, 9d, & 9f were also found to be more potent than the standard drugs acarbose, miglitol and deoxynojirimycin. Furthermore, these compounds were investigated by computational studies using the GLIDE docking module of the Schrödinger suite 2021-4 in which 9b and 9c showed more promising results than the standard drugs acarbose, miglitol, and deoxynojirimycin.

Revisiting salicylidene-based anion receptors.

Several salicylidene-based colorimetric and fluorimetric anion sensors are known in the literature. However, our 1H-NMR experimental results (in DMSO-d6) showed hydrolysis of imine (-N[double bond, length as m-dash]CH-) bonds in salicylidene-based receptors (SL, CL1 and CL2) in the presence of quaternary ammonium salts (n-Bu4N+) of halides (Cl- and Br-) and oxo-anions (H2PO4 -, HSO4 - and CH3COO-). The mono-salicylidene compound CL1 showed the most extensive -N[double bond, length as m-dash]CH- bond hydrolysis in the presence of anions. In contrast, the di-salicylidene compound CL2 and the tris-salicylidene compound SL showed comparatively slow hydrolysis of -N[double bond, length as m-dash]CH- bonds in the presence of anions. Anion-induced imine bond cleavage in salicylidene compounds could easily be detected in 1H-NMR due to the appearance of the salicylaldehyde -CHO peak at 10.3 ppm which eventually became more intense over time, and the -N[double bond, length as m-dash]CH- peak at 8.9-9.0 ppm became considerably weaker. Furthermore, the formation of the salicylidene O-H⋯X- (X- = Cl-/Br-) hydrogen-bonded complex, peak broadening due to proton-exchange processes and keto-enol tautomerism have also been clearly observed in the 1H-NMR experiments. Control 1H-NMR experiments revealed that the presence of moisture in the organic solvents could result in gradual hydrolysis of the salicylidene compounds, and the rate of hydrolysis has further been enhanced significantly in the presence of an anion. Based on 1H-NMR results, we have proposed a general mechanism for the anion-induced hydrolysis of imine bonds in salicylidene-based receptors.

Three-component reaction between isatoic anhydride, amine and meth-yl-subs-tituted furyl-acryl-alde-hydes: crystal structures of 3-benzyl-2-[(E)-2-(5-methylfuran-2-yl)vin-yl]-2,3-di-hydro-quinazolin-4(1H)-one, 3-benzyl-2-[(E)-2-(furan-2-yl)-1-methyl-vin-yl]-2,3-di-hydro-quinazolin-4(1H)-one and 3-(furan-2-ylmeth-yl)-2-[(E)-2-(furan-2-yl)-1-methyl-vin-yl]-2,3-di-hydro-quinazolin-4(1H)-one.

Compounds (I), C22H20N2O2, (II), C22H20N2O2 and (III), C20H18N2O3 are the products of three-component reactions between isatoic anhydride, the corresponding amine and 3-(5-methylfuran-2-yl)- or (furan-2-yl)-2-methyl-acryl-aldehyde. Compound (I) crystallizes in the monoclinic space group P21/n, while compounds (II) and (III) are isostructural and crystallize in the ortho-rhom-bic space group Pbca. The tetra-hydro-pyrimidine ring in (I)-(III) adopts a sofa conformation. The NH nitro-gen atom has a trigonal-pyramidal geometry, whereas the N(R) nitro-gen atom is flattened. The furyl-vinyl substituents in (I)-(III) are practically planar and have an E configuration at the C=C double bond. In (I), this bulky fragment occupies the axial position at the quaternary carbon atom of the tetra-hydro-pyrimidine ring, whereas in (II) and (III) it is equatorially disposed. In the crystal of (I), mol-ecules form hydrogen-bonded chains propagating along [001] by strong inter-molecular N-H⋯O hydrogen bonds. The chains are packed in stacks along the a-axis direction. In the crystals of (II) and (III), mol-ecules also form hydrogen-bonded chains propagating along [100] by strong inter-molecular N-H⋯O hydrogen bonds. However, despite the fact that compounds (II) and (III) are isostructural, steric differences between the phenyl and furyl substituents result in chains with different geometries. Thus in the crystal of (II) the chains have a zigzag-like structure, whereas in the crystal of (III), they are almost linear. In both (II) and (III), the hydrogen-bonded chains are further packed in stacks along the b-axis direction.