Mono-substituted cyclodextrins

Recently, X-ray analysis of /J-cyclodextrin having a t-butyl-thio moiety at the C(6) position was reported as the first example of mono-substituted cyclodextrin (38). Interestingly, a single molecule of this cyclodextrin behaves as the host at its cavity, on the one hand, and also as the guest at the t-butyl moiety, on the other hand, as shown in Fig. 7. 

We have also examined the use of cyclodextrin-derived artificial enzymes in promoting bimolecular aldol reactions, specifically those of m-nitrobenzaldehyde (57) and ofp-t-butylbenzaldehyde (58) with acetone [141]. Here, we examined a group of mono-substituted cyclodextrins as catalysts (e.g. 59), as well as two disubstituted (3-cyclodextrins (e.g. 60) (10 catalysts in all). They all bound the aldehyde components in the cyclodextrin cavity and used amino groups of the substituents to convert the acetone into its enamine. An intracomplex reaction with 58 and hydrolysis of the enamine product then afforded hydroxyketone 61 (cf. 62). These catalysts imitate natural enzymes classified as Class I aldolases. 

Nitrile oxide cycloaddition with mono- and trisubstituted alkenes affords almost exclusively 5-mono- and 4,5,5-trisubstituted isoxazolines, respectively, the regioselectivity being determined by steric effects. Reverse regioselectivity in nitrile oxide cycloaddition to terminal alkenes has been reported <1997CC1517> for example, 4-A t/-butylbenzoni-trile oxide was forced to reverse alignment for the cycloaddition by formation of the inclusion complex 470 with /3-cyclodextrin. Under these conditions, 90% of the 3,4-disubstituted cycloadducts were obtained, whereas in the absence of cyclodextrin the aromatic nitrile oxide afforded only the 5-substituted isoxazoline. 

Interest in phosphorus-containing calixarenes continues. Structures reported include hexa(diethoxyphosphoryloxy)calix[6]arene (8), inherently chiral 1,2-bridged calix[4]arene diphosphates, and a calixarene like C3 symmetric receptor with a phosphate function at the cavity bottom. " The purification of phosphate substituted calixarenes has been studied by chiral HPLC and by normal reverse phase HPLC. Mono(6-0-diphenoxyphosphoryl)-P-cyclodextrin (9) and mono(6-0-ethoxyhydroxyphosphoryl)-p-cyclodextrin (10) have been synthesised and show enantioselective inclusion of D and L amino acids e.g. 3.6 for D/L serine in the case of 9). ... 

Heptakis 6-0-t-butyldimethylsilyl-P-cyclodextrin, on reaction with 4-chloro-methyl-A -methyl-2-nitroaniline, affords the mono-3-substituted benzyl ether. P-Cyclodextrin carrying a 2-(naphthylmethyl) group at 0-6 exists with the aromatic rings within the cavity to an extent which is very temperature dependent. Temperature can therefore be used to control the degree of complexing of the aromatic system with a fluorescent naphthalene compound. Heptakis-[2,3-di-0-acetyl-6-deoxy-6-iodo]-P-cyclodextrin treated with 6-methoxycarbonyl-2-naphthol allowed access to the compound having naphthoic acid substituents at all of the primary positions, and this forms a very stable 1 1 complex with a merocyanine laser dye which is a mimic of the antenna function in photosynthesis and shows promise as a photochemical microreactor. Mono-[6-0-(8-qui-nolyl)]-P-cyclodextrin has been reported, and the stabilities of inclusion complexes with amino acid guests have been described. ... 

An abbreviated route to heptakis 2,3-anhydro-D-man/io-P-cyclodextrin has been reported, and likewise a modified route to the per 3,6-anhydro-compound via the hepta-6-iodo derivative has been reported. A paper which reports the mono-2,3-a//o-anhydride and the mono-3,6-anhydride of P-cyclodextrin also reports the 2,3 -anhydro derivative with the anhydro ring linking two adjacent sugar units. Other Japanese workers have reported the derivative 35 containing a benzylidene acetal ring also linking the same 2,3 -hydroxyl positions of the heptakis-6-O-pivaloate of P-cyclodextrin. Clearly this work opens many opportunities for making further selectively substituted compounds, and the authors... 

In the area of cyclodextrin ethers the -compound has been converted into a set of five tris-Tbdms ethers, all substituted at their various 6-positions, which were separated by hplc and characterized by n.m.r. spectroscopy. Related work applied to y-cyclodextrin gave the various 6,6 -disubstituted ethers. 5-Bromo-l-pentene was used to produce the 2-0-mono-4-pentenyl ether of P-cyclodextrin which was then permethylated and the product was chemically bonded to silica gel to form an efficient hplc stationary phrase for the separation of enantiomers. Peroctyl a-cyclodextrin has been studied as a chiral receptor for the ephedrinium ion. Various octyl ethers of a-, P- and y-cyclodextrin ranging in their substitution from the diethers to completely alkylated products were characterized by electrospray mass spectrometry and n.m.r. methods applied to methylated derivatives. The 2,6-didodecyl derivative of p-cyclodextrin has been used as a potentiometric sensor. In the field of aromatic ethers, naphthyl carboxylate substituents have been bonded at the 6-positions and the products were able to transfer excitation energy to complexed merocyanine held in the cavities of those molecules. These phototransfer processes were extremely efficient.P-Substituted cyclodextrin derivatives with p-allyloxybenzoyl or various benzyl substituents at 0-2 or 0-3 were incorporated by hydrosilylation to give hydromethylpolysiloxane polymers used as chiral phases for chromatographic resolution of enantiomers. Cyclodextrins with complex benzyl-like eth are illustrated in 22 and 23. The latter were prepared as artificial redox enzymes. 

The concept of cyclodextrin guest inclusion has been extended to the synthesis of a library of multicavity dimers and trimers of cyclodextrin that can bind specific guest molecules to mimic enzymes (Figure 6) Such supramolecular structures were tested with mono-, di-, and tri-substituted Gd + complexes bearing hydrophobic cyclohexyl moieties for interaction with the cyclodextrin cavities. The relaxivity enhancement increased with the number of cyclohexyl groups on the Gd + chelate. Further, the cyclodextrin trimer host-guest supramolecule with the tri-substituted Gd " " complex exhibited the greatest relaxivity... 

Partial enzymic hydrolyses of substituted P-cyclodextrins using bacterial a-amylase have been described. From the mono-6-tosylate maltotriose carrying the ester group at the nonreducing terminal position was obtained, and from the mono-2,3-anhydro-D-a//o-compound the trimer bearing the anhydride ring in the central position was the product. This work is related to degradative studies with y-cyclodextrin and a different amylase (Vol. 24, p. 60, ref. 20). ... 

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