Synthesis of aryl enopyranones directly from glycals and aromatic halides to access 2-deoxy-ß-C-aryl glycosides.

An efficient synthesis of aryl enopyranones via an oxidative Heck-type coupling reaction between ether protected D/L-glycals and different aryl halides is developed. This one-step method attaches an aryl group at the C-1 position keeping the C-1/C-2 double bond intact via the Saegusa-Ito type oxidation, thus facilitating the synthesis of medicinally important 2-deoxy-ß-aryl-C-glycosides after Pd/C reduction.

Peroxodisulfate-assisted synthesis of 2-thiocyanato glycals and their transformation to C-2-thio acrylo/aryl nitrile-substituted glycals.

An efficient regioselective method to attach thiocyanato groups at the ß-position of enol double bonds in sugar enol ethers using KSCN and potassium persulfate has been developed. The highly regioselective addition of the resulting sugar thiocyanate to electron rich species like terminal alkynes and benzynes under Pd catalysis generated C-2-thio acrylo/aryl nitrile glycals via simultaneous introduction of thio and cyano groups into carbon-carbon triple bonds.

Switchable reactivity of 2-benzoyl glycals towards stereoselective access of 1-3 and 1-1 S/O linked disaccharides.

We have developed a synthesis of 1-3 and 1-1 disaccharides from 2-benzoyl glycal and anomeric thiol and/or hydroxy sugar acceptors under mild conditions at room temperature. The regio and stereo-selectivity of the newly formed inter-glycosidic linkages are dependent on the nature of the glycal donor (D or L) and anomeric acceptor.

Pd-catalyzed synthesis of hetero 1,2-interlinked C-disaccharides by coupling of iodo glycals with glycals.

A facile synthesis of C1-C2 interlinked disaccharides is achieved from readily available iodo-glycals and unsubstituted glycals. Ester-protected donors reacted with ether-protected acceptors under Pd-Ag catalysis to access C-disaccharides bearing C-3 vinyl ether, which upon ring opening by Lewis acid furnished pi-extended conjugated orthogonally protected chiral ketones. Benzyl deprotection and reduction of the double bonds resulted in a fully saturated disaccharide stable toward acid hydrolysis.

Ni-catalyzed domino transformation of enopyranoses and 2-iodo phenols/anilines to pyrano cis fused dihydro-benzofurans/indoles.

A Ni-catalyzed direct access to various pyrano cis-fused dihydro benzofurans and indoles from unsaturated enopyranoses and o-iodo phenols/anilines is developed. The domino synthesis of pyrano C2-C1 and C3-C2 cis-fused heteroarynes were achieved both from glycals and pseudo glycals in which heteroatoms are linked at C2 and C3 positions, respectively, with excellent chemo-selectivity.

Dual targeting of acetylcholinesterase and tau aggregation: Design, synthesis and evaluation of multifunctional deoxyvasicinone analogues for Alzheimer's disease.

Development of multitargeted ligands have demonstrated remarkable efficiency as potential therapeutics for Alzheimer's disease (AD). Herein, we reported a new series of deoxyvasicinone analogues as dual inhibitor of acetylcholinesterase (AChE) and tau aggregation that function as multitargeted ligands for AD. All the multitargeted ligands 11(a-j) and 15(a-g) were designed, synthesized, and validated by 1HNMR, 13CNMR and mass spectrometry. All the synthesized compounds 11(a-j) and 15(a-g) were screened for their ability to inhibit AChE, BACE1, amyloid fibrillation, α-syn aggregation, and tau aggregation. All the screened compounds possessed weak inhibition of BACE-1, Aß42 and α-syn aggregation. However, several compounds were identified as potential hits in the AChE inhibitory screening assay and cellular tau aggregation screening. Among all compounds, 11f remarkably inhibited AChE activity and cellular tau oligomerization at single-dose screening (10 µM). Moreover, 11f displayed a half-maximal inhibitory concentration (IC50) value of 0.91 ± 0.05 µM and half-maximal effective concentration (EC50) value of 3.83 ± 0.51 µM for the inhibition of AChE and cellular tau oligomerization, respectively. In addition, the neuroprotective effect of 11f was determined in tau-expressing SH-SY5Y cells incubated with Aß oligomers. These findings highlighted the potential of 11f to function as a multifunctional ligand for the development of promising anti-AD drugs.