Facile synthesis of a diverse library of mono-3-substituted β-cyclodextrin analogues

Abstract

Substituted cyclodextrins (CDs) have many applications, but synthetic challenges have limited the derivatives that can routinely be accessed. In particular, although there is considerable interest in selective derivatization at the 2-and 3-hydroxyls on the secondary face, since bulky guest molecules are most likely to project through this larger aperture, syntheses of such derivatives have required arduous procedures afforded with poor yields. We address this challenge via synthetic strategies that allow facile creation of diverse libraries of water soluble mono-3-substituted-β-cyclodextrins. The power of these strategies is confirmed through synthesis of twenty water-soluble cyclodextrin analogues with amide, thioureas or urea linkers, using one-pot reactions producing ≥ 55% yields and purifications that do not require chromatography. This work opens new possibilities for the design of selective host molecules for use in supramolecular chemistry, chemical separations, pharmaceutical formulations, and calibration of molecular simulations.

Adamantane Functionalized Poly(2-oxazoline)s with Broadly Tunable LCST-Behavior by Molecular Recognition

“…Most notable is the utilization of various macrocycles, such as cucurbit [7]urils [40], pillararenes [41,42], and cyclobis(paraquat-pphenylene)s [43,44] to modulate the LCST behavior of thermoresponsive polymers through complexation with polymer termini or side chains [40,[45][46][47][48][49][50][51]. Among these different hosts, cyclodextrins have been prominently featured for the modulation of thermoresponsive behavior, as they can accommodate a wide variety of hydrophobic guest molecules, have an extensively studied complexation chemistry, and various sizes (α, β, and γcyclodextrin) [52] and chemical variants are commercially available or can be readily prepared [53,54]. In addition, cyclodextrins and several of their derivatives are generally recognized as safe, which is ideal for biomedical applications [55,56].…”

Parallel Synthesis and Screening of Supramolecular Chemosensors That Achieve Fluorescent Turn-on Detection of Drugs in Saliva

“…Parallel synthesis is widely used in medicinal chemistry to screen a broad structural space around a certain structural motif. Parallel synthesis of host-type molecules has been used to screen for binding properties, catalysis, and/or photochemical properties , with the parallelization often provided by metal–ligand coordination. − Sensors created by parallel synthesis approaches have typically been inorganic or polymer based. − Organic dyes are often prepared via parallel synthesis, while some examples exist of a parallel search for discrete organic molecules that sense a particular target. − One example of particular interest involved the condensation of a set of aromatic aldehydes with a set of heterocyclic nucleophiles to form 276 fluorescent styryl dyes . The reaction mixtures were tested directly in cells for organelle accumulation, although no particular sensing mechanism or analyte binding functions were included in the library design.…”