Natural Products & Bioactivity Inspired Synthetic Pursuits Interfacing with Carbohydrates: Ongoing Journey with C‐Glycosides

• Published in: Chemical record 2021-11, Vol.21 (11), p.3131-3177
• Main Authors: Singh Aidhen, Indrapal, Thoti, Naveenkumar
• Format: Article
• Language: English
• Subjects: 3-glycosylated isocoumarins; acyl C-β-D-Glucosides; Acyl-anions; Aldehyde reductase; Alkanes; Anions; Aromatic compounds; benzyl C-β-D-Glucosides; Biological activity; C-Glycosides; Carbohydrates; Cell surface; Chemical synthesis; Diabetes mellitus; Drug discovery; Glucosides; Glycosides; Inhibitors; Ketones; Lipophilic; Natural products; Reductases
• ISSN: 1527-8999; 1528-0691
• DOI: 10.1002/tcr.202100216

Natural products, remains the most important source for the discovery of new drugs for the treatment of human diseases. This has inspired the synthetic community to design and develop mimics of natural products either to answer important questions in biology or to explore their therapeutic potentials. Glycosides present themselves abundantly in nature, right from the cell surface receptors to natural products of any origin. The O‐Glycosides are hydrolytically less stable compared to C‐glycosides and this feature has presented a great opportunity for drug discovery. The discovery of Dapagliflozin, an SGLT inhibitor and C‐glucoside, for the treatment of diabetes is one such example. Aryl acyl‐anion chemistry has been explored for the synthesis of 2‐deoxy‐C‐aryl furanoside/pyranoside/septanosides. Besides success, the studies have provided valuable insight into the natural propensities of the architectural framework for the cascade to furan derivatives. The aryl acyl‐anion chemistry has also enabled the synthesis of biologically active diaryl heptanoids. Inspired from sucesss of Dapagliflozin, new analogues have been synthesized with pyridine and isocoumarin heterocycle as the proximal ring. C‐glucosides of isoliquiritigenin have been synthesized for the first time and evaluated as an efficient aldose reductase inhibitor. The synthesis and evaluation of acyl‐C‐β‐D‐glucosides and benzyl‐C‐β‐D‐glucoside as glucose‐uptake promoters has revealed promise in small molecules. The concept of building blocks has been used to obtain natural oxylipins, D‐xylo and L‐xylo‐configured alkane tetrols and novel lipophilic ketones with erythro/threo configured trihydroxy polar head‐group as possible anti‐mycobacterial agents. Synthetic pursuits towards 2‐deoxy‐C‐arylpyranosides/furanosides and C‐glycosides in general are described herein. The former has banked on the use of acyl‐anion chemistry, while the synthesis of the later is inspired from their biological activity and therapeutic significance.