A convenient method for functionalization of the 2-position of cyclodextrins

doi:10.1016/S0040-4039(00)97599-3

Tetrahedron Letters

Volume 31, Issue 30, 1990, Pages 4275-4278

https://doi.org/10.1016/S0040-4039(00)97599-3 Get rights and content

Abstract

A new convenient strategy for functionalization of the 2-position of cyclodextrins involving deprotonation of cyclodextrin by sodium hydride followed by a nucleophilic attack of the resultant cyclodextrin oxyanion on the desired electrophile gives a high yield of the cyclodextrin derivative.

Deprotonation of cyclodextrin by NaH followed by a nucloephilic attack of the resultant cyclodextrin oxyanion on the desired electrophile gives a high yield of cyclodextrin functionalized at the 2-position.

References (16)

T. Murakami et al.
Tetrahedron Lett.
(1987)
k. Takahashi et al.
Tetrahedron Lett.
(1984)
L.D. Melton et al.
Carbohydrate. Res.
(1971)
A. Ueno et al.
Tetrahedron Lett.
(1982)
M.L. Bender et al.
(1978)
V.T. D'Souza et al.
Acc. Chem. Res.
(1987)
K. Fujita et al.
J. Am. Chem. Soc.
(1986)
K. Take et al.
Carbohydrate Chem.
(1988)

There are more references available in the full text version of this article.

Cited by (182)

Development of nanoparticles based on amphiphilic cyclodextrins for the delivery of active substances
2024, International Journal of Pharmaceutics
Although amphiphilic cyclodextrin derivatives (ACDs) serve as valuable building blocks for nanomedicine formulations, their widespread production still encounters various challenges, limiting large-scale manufacturing. This work focuses on a robust alternative pathway using mineral base catalysis to transesterify β-cyclodextrin with long-chain vinyl esters, yielding ACD with modular and controlled hydrocarbon chain grafting. ACDs with a wide range of degrees of substitution (DS) were reliably synthesized, as indicated by extensive physicochemical characterization, including MALDI-TOF mass spectrometry. The influence of various factors, including the type of catalyst and the length of the hydrocarbon moiety of the vinyl ester, was studied in detail. ACDs were assessed for their ability to form colloidal suspensions by nanoprecipitation, with or without PEGylated phospholipid. Small-angle X-ray scattering and cryo-electron microscopy revealed the formation of nanoparticles with distinct ultrastructures depending on the DS: an onion-like structure for low and very high DS, and reversed hexagonal organization for DS between 4.5 and 6.1. We confirmed the furtivity of the PEGylated versions of the nanoparticles through complement activation experiments and that they were well tolerated in-vivo on a zebrafish larvae model after intravenous injection. Furthermore, a biodistribution experiment showed that the nanoparticles left the bloodstream within 10 h after injection and were phagocytosed by macrophages.
Cyclodextrin regulated natural polysaccharide hydrogels for biomedical applications-a review
2023, Carbohydrate Polymers
Cyclodextrin and its derivative (CDs) are natural building blocks for linking with other components to afford functional biomaterials. Hydrogels are polymer network systems that can form hydrophilic three-dimensional network structures through different cross-linking methods and are developing as potential materials in biomedical applications. Natural polysaccharide hydrogels (NPHs) are widely adopted in biomedical field with good biocompatibility, biodegradability, low cytotoxicity, and versatility in emulating natural tissue properties. Compared with conventional NPHs, CD regulated natural polysaccharide hydrogels (CD-NPHs) maintain good biocompatibility, while improving poor mechanical qualities and unpredictable gelation times. Recently, there has been increasing and considerable usage of CD-NPHs while there is still no review comprehensively introducing their construction, classification, and application of these hydrogels from the material point of view regarding biomedical fields. To draw a complete picture of the current and future development of CD-NPHs, we systematically overview the classification of CD-NPHs, and provide a holistic view on the role of CD-NPHs in different biomedical fields, especially in drug delivery, wound dressing, cell encapsulation, and tissue engineering. Moreover, the current challenges and prospects of CD-NPHs are discussed rationally, providing an insight into developing vibrant fields of CD-NPHs-based biomedicine, and facilitating their translation from bench to clinical medicine.
Proton-regulated alcohol oxidation for high-capacity ketone-based flow battery anolyte
2023, Joule
Redox flow batteries have a unique architecture that potentially enables cost-effective long-duration energy storage to address the intermittency introduced by increased renewable integration for the decarbonization of the electric power sector. Targeted molecular engineering has demonstrated electrochemical reversibility in natively redox-inactive ketone molecules in aqueous electrolytes. However, the kinetics of fluorenone-based flow batteries continue to be limited by slow alcohol oxidation. We show how strategically designed proton regulators can accelerate alcohol oxidation and thus enhance battery kinetics. Fluorenone-based flow batteries with the organic additive β-cyclodextrin demonstrate enhanced rate capability, high capacity, and long cycling. This study opens a new avenue to improve the kinetics of aqueous organic flow batteries by modulating the reaction pathway with a homogeneous catalyst.
Dexamethasone Sodium Phosphate Loaded Modified Cyclodextrin Based Nanoparticles: An Efficient Treatment for Rheumatoid Arthritis
2021, Journal of Pharmaceutical Sciences
The main aim of the current research was to develop a modified cyclodextrin based nanoparticulate drug delivery system to deliver dexamethasone sodium phosphate (DSP) for the treatment of rheumatoid arthritis (RA). DSP is a glucocorticoid (GC), and its limited application in RA therapy due to poor pharmacokinetics and its severe associated side effects. DSP loaded hydrophobically modified cyclodextrin based nanoparticles (DSP-NPs) prepared by a double emulsion solvent evaporation method. The nanoparticle size was <120 nm, good entrapment efficiency and excellent stability were obtained. TEM study showed that nanoparticles were perfectly spherical shape. The in-vitro drug release from nanoparticle follows the non-Fickian diffusion mechanism. The pharmacokinetic profile of DSP after encapsulation showing the 2.3-fold increase in AUC and extended mean residence time, which increases the chances of nanoparticles to extravasate into the site of inflammation by the EPR effect. The pharmacodynamic studies in the Adjuvant-induced Arthritis (AIA) rat model showing a significant reduction in arthritic score, paw thickness, and inflammatory cytokine level in serum. Adverse effects evaluation studies demonstrate a significant reduction in the associated undesirable effects on body weight, blood glucose level, renal impairment, and hematological abnormalities compared to marketed formulation. These results suggest that DSP-NPs can be used as an efficient therapy for RA.
Polycyclodextrins: Synthesis, functionalization, and applications
2020, Carbohydrate Polymers
Cyclodextrins (CDs) are cyclic oligosaccharides with unique conical structure enabling host-guest inclusion complexes. However, virgin CDs sufferfrom low solubility, lack of functional groups and its inability to strong complexation with the guests. One of the most efficient ways to improve the properties of cyclodextrins is the synthesis of polycyclodextrins. Generally, there are two types of polycyclodextrins: 1) polymers containing CD units as parts of the main backbone; and 2) polymers with CD units as side chains. These polycyclodextrins are produced (i) from direct copolymerization of virgin cyclodextrins or cyclodextrins derivatives with various monomers including isocyanates, epoxides, carboxylic acids, anhydrides, acrylates, acrylamides and fluorinated aromatic compounds, or (ii) by post-functionalization of other polymers with CDs or CD derivatives.. By selecting the proper derivatives of CDs and controlling the polymerization, polycyclodextrins with linear, hyperbranched, and crosslinked structures have been synthesized. Polycyclodextrins have found significant applications in numerous areas, as adsorbents for removal of organic pollutants, carriers in gene/drug delivery, and for preparation of supramolecular based hydrogels. The focus of this review paper is placed on the synthesis, characterization, and applications of CDs so as to highlight challenges as well as the promising features of the future ahead of material developments based on CDs.
A stimuli-responsive insulin delivery system based on reversible phenylboronate modified cyclodextrin with glucose triggered host-guest interaction
2018, International Journal of Pharmaceutics
Injection of insulin is an effective therapy to treat most patients with the type I diabetes and some with type II diabetes. Additionally, the release of insulin under specific conditions has attracted widespread interest. In this study, a smart drug carrier that can release insulin depending on the changes in blood glucose levels was designed. Combining two popular molecules through facile synthetic processes, a drug carrier of reversible phenylboronate group modified cyclodextrin (β-CD-EPDME) was fabricated. The drug carrier is composed of cyclodextrin, which can encapsulate insulin, and phenylboronate, which is sensitive to the cis-diols in some saccharides. Moreover, β-CD-EPDME can successfully encapsulate insulin and almost completely release insulin in the presence of glucose. The detached phenylboronic acid moiety triggered by glucose can attack the β-CD cavity and form a host-guest complex, which can force out the encapsulated insulin within the cavity. In addition, the insulin released from the β-CD-EPDME@Insulin complex retains its secondary structure, and the drug carrier has been proven to have low cytotoxicity. Thus, this safe and glucose-responsive drug carrier shows the potential for use in the therapy of diabetes.

View all citing articles on Scopus

View full text

A convenient method for functionalization of the 2-position of cyclodextrins

Abstract

Tetrahedron Lett.

Tetrahedron Lett.

Carbohydrate. Res.

Tetrahedron Lett.

Acc. Chem. Res.

J. Am. Chem. Soc.

Carbohydrate Chem.