An efficient taurine-catalyzed
green multicomponent approach has
been described for the first time to synthesize densely substituted
therapeutic core dihydropyrano[2,3-c]pyrazoles. Applications
of the developed synthetic strategies and technologies revealed the
synthesis of a series of newly designed 1,4-dihydropyrano[2,3-c]pyrazoles containing isonicotinamide, spirooxindole, and
indole moieties. Detailed in silico analysis of the
synthesized analogues revealed their potential to bind wild-type and
antibiotic-resistant variants of dihydrofolate reductase, a principal
drug target enzyme for emerging antibiotic-resistant pathogenic Staphylococcus aureus strains. Hence, the synthesized
dihydropyrano[2,3-c]pyrazole derivatives presented
herein hold immense promise to develop future antistaphylococcal therapeutic
agents.
An ecofriendly, inexpensive,
and efficient route for synthesizing
3,3′-bis(indolyl)methanes (BIMs) and their derivatives was
carried out by an electrophilic substitution reaction of indole with
structurally divergent aldehydes and ketones using taurine and water
as a green catalyst and solvent, respectively, under sonication conditions.
Using water as the only solvent, the catalytic process demonstrated
outstanding activity, productivity, and broad functional group tolerance,
affording the required BIM natural products and derivatives in excellent
yields (59–90%). Furthermore, in silico based structure activity
analysis of the synthesized BIM derivatives divulges their potential
ability to bind antineoplastic drug target and spindle motor protein
kinesin Eg5. The precise binding mode of BIM derivatives with the
ATPase motor domain of Eg5 is structurally reminiscent with previously
reported allosteric inhibitor Arry520, which is under phase III clinical
trials. Nevertheless, detailed analysis of the binding poses indicates
that BIM derivatives bind the allosteric pocket of the Eg5 motor domain
more robustly than Arry520; moreover, unlike Arry520, BIM binding
is found to be resistant to drug-resistant mutations of Eg5. Accordingly,
a structure-guided mechanism of Eg5 inhibition by synthesized BIM
derivatives is proposed.
A square-planar [Cu II L] complex 1, based on the redox-active phenalenyl unit LH 2 = 9,9′-(ethane-1,2diylbis(azanediyl))bis(1H-phenalen-1-one), is prepared and structurally characterized by single-crystal X-ray diffraction analysis. Complex 1 crystallizes at room temperature with the P1 space group. The molecular structure of 1 reveals the presence of intriguing C−H•••Cu intermolecular anagostic interactions of the order ∼2.7715 Å. Utilizing the presence of anagostic interactions and the free nonbonding molecular orbitals (NBMOs) of the closed-shell phenalenyl unit in 1, the oxidation reactions of some industrially important polycyclic aromatic hydrocarbons (PAHs) in the presence of the [Cu II L] complex under very mild conditions have been reported. The direct conversion of anthracene-9-carbaldehyde to 9,10-anthraquinone in one step concludes that the catalyst shows dual activity in the chemical transformations. This also includes the first report of a "single-step" catalytic transformation of pyrene-1carbaldehyde to the synthetically difficult pyren-4-ol, a precursor for the synthesis of several novel fluorescent probes for cell imaging.
The class of Double Diels‐Alder (DDA) reactions leading the targets concisely where numerous synthetic pursuits have been rewarded with conceptually novel and streamlined methods. After the tremendous development and discoveries in various Diels‐Alder reactions including its key role applications in many natural products syntheses, the DDA reaction is considered as a growing branch of Diels‐Alder reaction where two consecutive [4+2] cycloadditions trigger the streamlined construction of polycyclic and macrocyclic architectures. In light of the ever‐increasing importance of DDA reactions in chemical sciences, we review the comprehensive studies and recent advances in DDA reactions in organic synthesis. This review summarizes key achievements of DDA for the preparation of macrocyclic, bicyclic, heterocyclic, and polycyclic structures documented since its revelation in 1980 to 2020. Emphasis is put on the synthesis of various structural classes based on the selectivity of the DDA reaction.
For the first time, an eco-friendly and efficient onepot green multicomponent approach has been described to synthesize functionalized trans-2, 3-dihydrofuro[3,2-c]coumarins (DHFCs). In this synthesis, imidazole and water were used as the catalyst and solvent, respectively, under mild conditions. Applications of the developed catalytic process in a water medium revealed the outstanding activity, productivity, and broad functional group tolerance, affording a series of newly designed DHFC and derivatives in excellent yields (72−98%). Moreover, the human serum albumin (HSA) binding ability of the synthesized DHFC derivatives has been uncovered through the detailed in silico and in vitro-based structure-activity analysis. The ability to bind HSA, the most abundant serum protein, in the low micromolar ranges unequivocally reflects the suitable absorption, distribution, metabolism, and elimination profile of the synthesized compounds, which may further be envisaged for their therapeutic usage endeavors.
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