Carbohydrate drugs: current status and development prospect

α-d-Glucopyranosyl-(1→2)-[6-O-(l-tryptophanyl)-β-d-fructofuranoside]

“…The to H-4, C-2, C-3, C-3a and C-7a to 1NH, C-3, C-3a and C-7a to H-2, C-3a, C-4 and C-5 to H-7, C-3a and C-7 to H-5 and finally C-4, C-5 and C-7a to H-6. In the 13 C NMR spectrum, the presence of several peaks between 65-95 ppm suggested the presence of sugar moieties in compound (1). The gHMBCAD correlations C-10 to H-5 and H-6 and the chemical shifts of C-10 and C-6' provided direct proof of attachment of the tryptophan residue to a sugar through an ester bond.…”

“…The gHMBCAD correlation C-2′ to H-1′′ helped to solve the rest of the structure, which was shown to be an α-D-glucopyranose ring after similar examination of the sugar ring, which is explained above.The α-D-glucopyranose ring carbon chemical shifts were δC 91.8 (C-1′′), 71.7 (C-2′′), 72.8 (C-3′′), 69.9(C-4′′), 72.9 (C-5′′) and 60.5 (C-6′′) and δH 5.19 (1H, d, J = 4.1 Hz, H-1′′), 3.20 (1H, dd, J = 9.7, 3.9 Hz, H-2′′), 3.49 (1H, t, J = 9.3 Hz, H-3′′), 3.14 (1H, t, J = 9.4 Hz, H-4′′), 3.65 (1H, ddd, J = 9.7, 4.7, 2.4 Hz, H-5′′), 3.52 (1H, dd, J = 10.0, 4.8 Hz, H-6′′) and 3.50 (1H, dd, J = 10.0, 2.6 Hz, H-6′′), respectively. The gCOSY correlations H-2′′/H-1′′, H-4′′/H-5′′ and H-4′′/H-3′′ supported by many 2D-TOCSY correlations that include H-1′′/H-3′′, H-1′′/H-2′′, H-4′′/H-5′′, H-2′′/H-5′′, H-4′′/H-6′′, H-2′′/H-3′′, H-4′′/H-2′′, H-5′′/H-2′′, H-2′′/H-4′′, H-5′′/H-4′′, H-3′′/H-4′′, H-6′′/H-5′′, H-6′′/H-4′′, H-4′′/H-1′′, H-2′′/H-1′′, H-5′′/H-1′′ and gHMBCAD correlations C-5′′to H-1′′, C-4′′ to H-3′′, C-5′′ to H-4′′, C-2′′ to H-3′′ and C-6′′ to H-4′′ provided proof of structure for the α-D-glucopyranose ring moiety in compound(1). The absence of correlations in the 1 H-1 H ROESY data, indirectly confirms the disposition of the protons in both the β-D-fructofuranose and α-Dglucopyranose rings.…”

“…Carbohydrate-based natural products constitute a very potent group of compounds with promising prospects as future drugs [1]. Currently, there are many carbohydrate natural product derived compounds that are already drugs and these include: The polysaccharides, tragacanth (diarrhea and constipation) [2], astragalus (cancer) [3], lentinan (cancer and hepatitis B) [4], tremella (cancer and chronic bronchitis) [5,6], icodextrin (peritoneal dialysis) [7] and pentosan polysulfate (interstitial cystitis) [8]; the oligosaccharides, lactulose (constipation and hepatic encephalopathy) [9], sucralfate (active duodenal ulcers) [10]; and the monosaccharides, miglitol (anti-diabetic) [11] and meglumine (excipient) [12].…”

C-Linked Glycomimetic Libraries Accessed by the Passerini Reaction

“…Moreover, carbohydrates represent attractive chiral synthons susceptible to diverse modifications and transformations, a highly desirable feature in diversity-oriented synthesis [5] and in the synthesis of chiral catalyst systems [6] or of noncovalent systems built upon weak interactions [1]. Carbohydrates are still a relatively untapped pool of new therapeutics [7,8]; however, advances in the functional understanding of carbohydrate-involving biological processes enabled carbohydrates to take over a prominent role in drug design. A particular group of compounds, glycomimetics, has emerged in the response to the growing demand for highly specific structures aimed to probe biological processes or interfere with them [9].…”

New Mechanism for Release of Endosomal Contents: Osmotic Lysis via Nigericin-Mediated K+/H+ Exchange

“…1 This shift toward biologics has been driven by both the diversity of biologic molecules that can be exploited for pharmacologic applications (e.g., oligonucleotides, 2 genes, 3 proteins, 4,5 peptides, 6 carbohydrates, 7,8 immune conjugates, 9–11 synthetic biopolymers, 12 etc.) and the increased numbers of diseases for which biologic therapies seem well suited.…”