Large‐Ring Cyclodextrins as Chiral Selectors for Enantiomeric Pharmaceuticals

Abstract

Large-ring cyclodextrins (CD) are cyclic glucans composed of 9o rm ore a-1,4-linked glucose units.T hey are minor side products of bacterial glucanotransferases (CGTases,E C2.4.1.19) and have previously been available only in very small amounts for studies of their properties in supramolecular complex formation reactions.W ee ngineered aCGTase to synthesizemainly large-ring CD facilitating their preparation in larger amounts.B yr eversed phase chromatography,w eo btained single CD samples composed of 10 to 12 glucose units (CD10, CD11, and CD12) with ap urity of > 90 %. Their identity was confirmed by high resolution mass spectrometry and fragmentation analysis.Wedemonstrated the non-toxicity of CD10-CD12 for human cell lines by ac ell proliferation assaya nd impedimetric monitoring.W et hen showed that CD10 and CD11 are efficient chiral selectors for the capillary electrophoretic separation of the enantiomeric pharmaceuticals fluvastatin, mefloquine,c arvedilol, and primaquine.CDa re a-1,4-linked cyclic glucans with ad egree of polymerization (DP) between 6t o> 100. Branched a-1,6-CD have also been described. [1] In contrast to larger CD,CD6, CD7, and CD8 (a-, b-, g-CD) have been studied extensively and are produced commercially. [2] They form cone-shaped structures with ahydrophobic cavity and an outer hydrophilic area, enabling the reversible binding of hydrophobic mole-Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Cyclodextrins in Drug Delivery Systems and Their Effects on Biological Barriers

“…The α-, β-, and γ-cyclodextrins are widely known, which contain 6, 7, and 8 units respectively. Recently the smallest cyclodextrins were synthetized, containing 3 and 4 glucopyranose units [2], and on the other hand big oligosaccharides with more, than 8 units are also known [1] and applied for complexation [3] or as chiral selectors for enantiomeric pharmaceuticals [4]. Glucopyranose units form a conical cylinder, which has a hydrophobic inner cavity and a hydrophilic outer surface.…”

Molar mass effect in food and health

“…Cyclodextrins (CDs) composed of 6, 7 and 8 glucopiranose units α-CD, β-CD, and γ- CD are produced commercially. They form cone-shaped structures with a hydrophobic cavity and an outer hydrophilic area, enabling the reversible binding of hydrophobic molecules in their cavity to form supramolecular host-guest complexes ( Sonnendecker et al, 2019 ). They are used to encapsulate food flavours and aromas, orange aroma by α-cyclodextrin, d -limonene, menthol, and shiitake flavour byβ-CD, and encapsulated aromas are stable during storage ( Fenyvesi & Szente, 2016 ).…”

“…Large ring CD up to DP 37 has been prepared, and proved non-toxic, but is not produced in a great quantity. Sonnendecker et al (2019) reported that CDs with DP = 10 and 11 were effective for the enantiomeric separation of several enantiomeric pharmaceuticals ( Sonnendecker et al, 2019 ). Although the larger CDs were thought to be unsuitable for enatiomeric discrimination because of the increasing flexibility of larger CD rings, CD10 (CD with DP = 10) to CD12 (CD with DP = 12) were believed to be different from CD6 (α-CD) to CD8 (γ-CD) while still providing sufficient rigidity to form stable complexes.…”

“…Although the larger CDs were thought to be unsuitable for enatiomeric discrimination because of the increasing flexibility of larger CD rings, CD10 (CD with DP = 10) to CD12 (CD with DP = 12) were believed to be different from CD6 (α-CD) to CD8 (γ-CD) while still providing sufficient rigidity to form stable complexes. Thus, CD10 to CD12 were thought to act as chiral selectors ( Sonnendecker et al, 2019 ). Therefore, the flexibility is thought important for the performance of larger ring CDs.…”

Dynamic chiral cyclohexanohemicucurbit[12]uril

“…Cyclodextrins (CDs) containing more than 9 glycose units, referred to as large-ring CDs (LR-CDs), 4 can assume a helical folding arrangement, e.g., the 26-membered CD. [5][6][7][8][9] LR-CDs with 14 units have been shown to adopt a conformation that resembles a concave polygon. 10,11 Large pillar[n]arenes, where n = 8-10, containing up to 10 monomers in their structures, also adopt concave polygon shapes.…”