A convenient and scalable synthetic approach has been developed for the synthesis of acyl‐C‐β‐d‐glucosides and benzyl‐C‐β‐d‐glucosides. The use of Weinreb‐amide (WA) functionality was crucial for this accomplishment as the other apparently capable alternatives, had severe limitations for the access to acyl‐C‐glucosides. The synthesized compounds, acyl and benzyl‐C‐glucosides promote glucose‐uptake activity in the C2C12 (mouse skeletal muscle) cell lines through PPAR‐γ mediated GLUT4 expression. The developed synthetic scheme for acyl‐and benzyl‐C‐β‐d‐glucosides and biostudies evaluating their activity as glucose‐uptake promoters are disclosed herein.

Inspired from natural product isoliquiritine, an O‐glucoside and the corresponding aglycon chalcone, isoliquiritigenin (ISL), several C‐glucosylated chalcones and dihydrochalcones have been synthesized and evaluated for aldose reductase (AR) inhibition activity, for the first time. The initial inputs from molecular docking studies were also encouraging. Claisen‐Schmidt condensation reaction between 4‐C‐glucosylated benzaldehyde, a key building block developed during the synthetic efforts and acetophenones enabled convenient access to the targeted compounds in good yields. Excellent AR inhibition has been observed with C‐glucosylated ISL with IC50 value of 21 µM. This is similar to the chalcone ISL, displaying IC50 of 19 µM. In the light of limited aqueous solubility of ISL, the observed AR inhibition with C‐glucosylated ISL, gains importance. Additionally, the studies have revealed significance of the oxygenation pattern on the aromatic residue and paved way for the identification of few more new compounds with equally promising AR inhibition.

Convenient synthesis of 2‐β‐d‐Glucopyranosylpyridines has been achieved by using Bohlmann–Rahtz heteroannulation reaction between a sugar alkynone and ethyl β‐aminocrotonate. The synthesized compounds are analogues of Dapagaliflozin, an approved drug for lowering of blood glucose levels through inhibition of sodium‐glucose transporters in the kidney.

β‐Glucogallin 1 (BGG), a major component isolated from the Indian gooseberry (Emblica officinalis) medicinal plant, is a potent and selective inhibitor of aldose reductase (AKR1B1). Structurally, BGG is a glucosyl‐1‐ester, wherein gallic acid is linked to the β‐d‐glucose ring through an ester functionality. Susceptibility of the easily hydrolysable ester functional group in aqueous solution has been a cause of concern. Isosteric replacement of glucosyl‐O‐ with –NH– has offered the more stable and potent analogue 2; however, the C‐analogue 3, wherein a –CH2– unit replaces the glucosyl‐O, remains unexplored. Synthesis of C‐analogues 3 and 4 and their aldose reductase inhibition (ARI) constitutes the work presented herein.

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