Ramaswamy Ravichandran

Inclusion of Ring A of Cholesterol Inside the β-Cyclodextrin Cavity: Evidence from Oxidation Reactions and Structural Studies

The disposition of cholesterol inside the β-cyclodextrin cavity(β-CD) was deduced from oxidation of cholesterol secondary alcoholgroups by Ca(OCl)2 and H2O2 in thepyridine–acetic acid system. The amount of cholest-4-ene-3-one formedwas found to be proportional to the concentration of β-cyclodextrin,resulting in 56.1% of ketone. The oxidation rate was enhanced byβ-cyclodextrin and its methyl, polymer and 1 : 1copper(II)–β-cyclodextrin derivatives. Detailed investigationsinvolving UV-visible, 13C- and 1H-NMR(T1, 1D NOE and ROESY) spectroscopic studies were carried out.A binding constant value of 15,385 ± 1500 M-2 wasobtained for the 2 : 1heptakis-2,6-di-O-methyl-β-cyclodextrin(DMβ-CD) : cholesterolcomplex in chloroform from UV studies. Proton and solid state13C-CP MAS spectra of the β-CD–cholesterol mixtureshowed large magnitude shifts for the protons from the wider end of theβ-CD cavity as well as those of ring A and ring B of cholesterol. Both1D NOE and ROESY measurements indicated the proximity between ring A andring B protons of cholesterol and the wider end protons of β-CD andDMβ-CD. Besides, analysis of τc,τi and tau;m from T1measurements showed not only a lowering of rotational motions but a ξvalue of 0.016–0.048 for some of the cholesterol protons, typical of aweak complex. Based on these studies, a probable structure for the 2 : 1complex involving two molecules of β-CD/DMβ-CD was proposed withportions of ring A and ring B being present inside the wider end of theβ-CD/DMβ-CD cavity and ring D and the side chain attached atposition 17, projecting into the wider end of the secondβCD/DMβ-CD molecule.

Stereoselective reduction of menthone with sodium dithionite in the presence of β-cyclodextrin

Abstract The effect of β-cyclodextrin (BCD) and its methyl and polymer derivatives on the stereoselective reduction of menthone was studied. Modification of the yield and the proportion of epimeric alcohols formed were found to be the salient features of this reaction. Reduction of menthone in aqueous solution in presence of heptakis-2,6-di- O -methyl-β-cyclodextrin (DMBCD) remarkably enhanced the yield to 68% (from 10%) resulting in a menthol/neomenthol ratio of 1:2.5. Aqueous DMF (1:1) as the solvent increased the yield from 14.0% in water to 76% in the presence of BCD, the menthol/neomenthol ratio being 1:3.6. Under phase transfer condition, DMBCD in water—benzene mixture gave 82.0% yield along with a good stereoselectivity compared to 47.0% in the absence of a phase transfer catalyst.

Stereoselective hydrogenation of (R)-( + )-pulegone and (2S, 5R)-(-)-menthone in presence of β-cyclodextrin and its derivatives

Abstract Stereoselective hydrogenation of (R)-(+)-pulegone and (2S,5R)-(−)-menthone over Raney nickel at room temperature with dilute and concentrated alkali in presence of β-cyclodextrin and its derivatives was studied. The effect of alkali and β-cyclodextrin and its derivatives on the modification of the yield and the proportion of epimeric alcohols formed were found to be the salient features of this reaction ( Scheme. 1 Download : Download high-res image (29KB) Download : Download full-size image Scheme. 1 . ).

Regulatory nature of β-cyclodextrin in selective ring-opening during reduction of styrene oxide

Abstract The cleavage of styrene oxide by different reagents like Raney nickel, palladium–carbon and sodium borohydride in the presence of β-cyclodextrin and its derivatives like β-CD-epichlorohydrin (β-CD-polymer) and heptakis-2,6-di-O-methyl-β-cyclodextrin (DMβ-CD) showed distribution in formation of ethylbenzene, 1-phenylethanol and 2-phenylethanol. Formation of deoxygenated products like styrene and ethylbenzene were suppressed by β-CD and its derivatives under hydrogenation over Raney nickel favouring increase in proportion of 2-phenylethanol. β-CD and its derivatives regulated increase in formation of 1-phenylethanol under reduction by Pd–C and NaBH4. Observed selectivities have been correlated to arise directly from the disposition adopted by styrene oxide inside the β-CD cavity, the nature and manner of which has been arrived at from the spectroscopic studies (UV and NMR) of inclusion.

β-Cyclodextrin and its derivatives mediate selectivity in reduction of (R)-(+)-pulegone with sodium dithionite

Pulegone is reduced in two stages by sodium dithionite—first to menthone and later to epimeric methols. The presence ofβ-cyclodextrin (BCD) and its derivatives resulted in more of the alcohols being formed. While the double bond was reduced predominantly in water, the ketone moiety was also reduced in a water-DMF mixture. A small percentage of menthone remained relatively unaffected in water-DMF even in the presence of BCD and its derivatives. Although no unreacted pulegone could be detected, exclusive alcohol formation was also not observed. Reduction of the double bond was found to be faster than that of the ketone.

β-Cyclodextrin mediated regioselective photo-Reimer–Tiemann reaction of phenols

Abstract In the presence of β-cyclodextrin and its derivatives, the photo-Reimer–Tiemann reaction of phenols with chloroform proceeded smoothly with high selectivity for the formation of 4-hydroxy benzaldehydes.

β-Cyclodextrin and its derivatives directed axial attack of hydride ion in the reduction of (R)-(+)-pulegone and (2S,5R)-(−)-menthone

Abstract Sodium borohydride reduction of ( R )-(+)-pulegone and (2 S ,5 R )-(−)-menthone in aqueous alkali resulted in formation of cis -pulegol from pulegone and menthol from menthone, in larger proportions in the presence of derivatives of β-cyclodextrin (BCD), namely, heptakis-2,6-di- O -methyl-β-cyclodextrin (DM-BCD) and BCD-epichlorohydrin polymer (BCD-polymer), implying axial attack of hydride ion being preferred in inclusion complexes of ( R )-(+)-pulegone and (2 S ,5 R )-(−)-menthone. Higher conversion yields were registered in reactions where BCD and its derivatives were present. More of double bond migrated product (isopulegol) was found to be formed from pulegone in the presence of BCD. The results obtained from the reactions are explained in terms of the orientation of pulegone and menthone arrived at from UV-Vis, 1 H and 13 C-NMR spectroscopic measurements. Binding constant values for the 1:2 (BCD or DMBCD:pulegone) complexes of BCD and DMBCD with pulegone were evaluated to be 5.428 ± 0.5 × 10 3 M −1 (BCD:pulegone) and 937 ± 50 M −1 (DMBCD:pulegone).

β-Cyclodextrin as inverse phase-transfer catalyst in oxidations of isoborneol, borneol and menthol by calcium hypochlorite in aqueous solution

Abstract The secondary alcohols, isoborneol, borneol and menthol can be converted to their ketones with solid Ca(OCl) 2 , in an aqueous medium, in the presence of β-cyclodextrin (BCD). The yield of product is linearly dependent on the BCD:substrate molar ratio, up to a maximum at equimolarity.

Selective hydroxymethylation of guaiacol in the presence ofβ-cyclodextrin

Studies on the effect ofβ-cyclodextrin (BCD) and its derivatives on the selectivity in hydroxymethylation of guaiacol by formaldehyde was carried out. Fairly high selectivity with respect to isovanillyl alcohol formation was achieved. Significantly, the selectivity-enhancing effects of 2,6-di-O-methyl-BCD was much larger, giving rise to 22% more of isovanillyl alcohol formation than BCD and its polymer. UV, fluorescence,1H-NMR spectroscopic and potentiometric studies were also carried out to determine the orientation of guaiacol inside the BCD cavity.