M. K. Grachev

Acetylation of α- and β-cyclodextrines

Applying acetyl chloride and versatile bases and solvents per- and regioacetylated derivatives of α- and β-cyclodextrines were prepared. Conditions were established for performing regiodirected acetylation of the primary hydroxy groups of α- and β-cyclodextrines in the presence of free secondary hydroxy groups.

Acetylation of secondary hydroxy groups of α- and β-cyclodextrines silyl derivatives

The application of acetyl chloride in the combination with different solvents and bases permitted the preparation of silyl derivatives of α- and β-cyclodextrines containing a definite amount of acetyl substituents on the secondary hydroxy groups. It was found that by means of the 1H and 13C NMR spectroscopy it is possible to make an exact attribution of acetyl groups to C2 or C3 carbon atoms of carbohydrate fragments of α- and β-cyclodextrines. Desilylation with ammonium fluoride in methanol gives acetyl derivatives of cyclodextrines containing free primary hydroxy groups.

β-cyclodextrin and its silyl derivative inclusion complexes and conjugates with medicine preparation “Ibuprofen” and its synthetic precursors

A possibility of formation of various inclusion complexes and conjugates of β-cyclodextrin and its silyl derivatives with the medicine preparation “Ibuprofen” and its synthetic precursors in dependence of nature of solvent and size of cyclodextrin cavity is demonstrated.

29Si NMR Spectroscopy as a Reliable Method for the Determination of Silyl Protective Groups Positions at the Cyclodextrin Frame

Abstract The synthesis of some new regioselectively silylated β-cyclodextrin derivatives is described. It is shown that by means of 29Si NMR spectroscopy it is possible to reliably determine the regioselectivity position of the silyl protective groups on the cyclodextrin frame and to control silylation of the cyclodextrin by utilizing chlorosilanes that have different sized substituents. GRAPHICAL ABSTRACT

The features of the synthesis and chemical behavior of some β-cyclodextrin silyl derivatives

Conditions are found for the regioselective silylation of the β-cyclodextrin primary hydroxy groups by diphenylmethylsilyl chloride and trimethylsilyl chloride. It is shown that the position of silyl substituents at the primary or secondary hydroxyl can be determined using 29Si NMR spectroscopy. In the case of acetic and phosphorous acid chlorides, the subsequent functionalization of the secondary hydroxyls occurs with a significant removal of the protective silyl groups.

Unusual regioselective acylation of the primary hydroxy groups of β-cyclodextrin

The reaction of β-cyclodextrin (1) with palmitoyl (2) and valeryl (4) chlorides in DMF or Py, unlike previously studied acetylation of 1, involves only the primary hydroxy groups of 1. The outcome of the reaction depends on the reaction conditions and the nature of the acid scavenger used (Et3N, Pri2NEt, PhNMe2, Py). 13C NMR spectroscopy was shown to be an effective tool in determining the number and position of aliphatic carboxylic acid residues introduced into 1. A hypothesis stating that preliminary formation of a reactive inclusion complex (acid chloride⊂1) is required for the acylation of 1 to occur is proposed and substantiated. This hypothesis provides a unified explanation for a variety of unusual facts observed in the acylation of 1 and its derivatives.

Synthesis and complex formation ability of monomeric and dimeric amphiphilic β-cyclodextrin derivatives

Applying 6-O-monotosyl derivative of β-cyclodextrin and hexane-1,6-diamine monomeric and dimeric (bridging) amphiphilic compounds were obtained, and the opportunity was demonstrated of the preparation on their basis of inclusion compounds at the interaction with 2-(4-isobutylphenyl)propionic acid (Ibuprofen).

Nanoscaled inclusion complexes of β-cyclodextrin with binuclear compounds based on diols containing fragments of selected aromatic monocarboxylic acids

Stable nanoscaled mono- and dimeric inclusion complexes of β-cyclodextrin with hosts based on symmetric diols of various length containing fragments of benzoic, nicotinic, or isonicotinic acid were synthesized.

Acylation of per-6-O-(tert-butyl)(dimethyl)silyl-α-cyclodextrin with acetylsalicylic chloride

Earlier, aiming to synthesize the conjugates of αand β-cyclodextrins containing drug residues at the cyclodextrin torus side occupied with secondary hydroxyl groups, we have performed acylation of per-6-О(tert-butyl)(dimethyl)silyl derivatives of α(I) and βcyclodextrin (II) at the second hydroxyl groups with chloroanhydrides of a series of aromatic monocarpboxylic acids, followed removal of protecting silyl groups [1, 2]. Acylation of the silyl derivatives I and II occurred with good yields in pyridine as well as (in the case of compound II) in DMF in the presence of N,Ndimethylaniline (method а) or С6Н6 (method b) in the presence of Et3N, the amines acting as the formed hydrogen chloride scavengers (Scheme 1).

Amphiphilic conjugates of β-cyclodextrin with acetylsalicylic and 2-(4-isobutylphenyl)propionic acids

New amphiphilic β-cyclodextrin derivatives containing pharmacologically important aromatic and aliphatic monocarboxylic acid fragments at both primary and secondary hydroxy groups were synthesized with the use of palmitic, acetylsalicylic, and 2-(4-isobutylphenyl)propionic acid chlorides. The position of the acyl groups in the carbohydrate fragments of β-cyclodextrin was determined by 13C NMR spectroscopy.