Carbohydrates as Scaffolds in Drug Discovery

Abstract

Drug discovery has long suffered from the difficulty of having to place pharmacophoric groups in just the right spatial arrangement to elicit the desired biological response. Although some molecule classes have been discovered that seem to be privileged structures for at least some drug-receptor interactions, there remains the challenge to design and synthesize molecules with high specific affinity to pharmacologically important targets. With their high density of stereochemical information and their relative rigidity, carbohydrates provide excellent platforms upon which to display a number of substituents in a sterically defined way, hence offering the opportunity to harness their unique features for the drug-discovery process. This review highlights the progress that has been made in the development of carbohydrate scaffolds for drug discovery.

1,2,4‐Trisubstituted Cyclopentanes as Platforms for Diversity

“…Removal of solvent and column chromatography (20:1 hexane/ethyl acetate) gave 21e as a white solid 2.87 g (12.1 mmol, 92%). 1 …”

“…Filtration, removal of the solvent in vacuo, and drying, gave 20.1 mg (0.11 mmol, 83%) of 12 as a white solid. 1 (1a,2b,4a)-1,2,4-Triazidocyclopentane (43) A 50 mL flask was charged with 10 mL DCM, 1 mL pyridine, and 248 mg 2,4-diazidocylopentanol 41 (1.48 mmol). Methanesulfonyl chloride (115 mL, 1.63 mmol) was added into the flask at ice-bath temperature and the mixture was stirred at 08C for 3 h. Ten milliliter of ethyl acetate was added and the organic phase washed with 10 mL cold water.…”

“…The solvent was removed and the residue was separated on a silica gel column to give 150 mg (0.78 mmol, 53% in two steps) 43 as a colorless liquid (10:1 hexane/ethyl acetate). 1 …”

“…The solvent was removed and the residue separated by silica gel column chromatography (10:1 hexane/ethyl acetate) to yield 850 mg (4.0 mmol, 75%) of 21f as a white solid. 1 …”

“…Functionalized cyclopentanes have considerable potential in this regard. Functionalized with multiple hydroxy groups, they may be considered as mimics of the natural monosaccharides, which have been extensively explored as scaffolds for chemical libraries [1,2].…”