Syntheses of novel cyclodextrin derivatives and their applications in depletion of lipids.

Ning Zhong, City University of New York, Graduate Center

Abstract

This dissertation presents the syntheses of novel cyclodextrin derivatives and their applications in depletion of lipids.;Chapter 1 presents the synthesis of a widely used synthon, 6A -O-p-toluenesulfonyl-beta-cyclodextrin (CDOTs). Parts of Chapter 1 have been published in copyrighted journals A & C 1 (see page vii).;Chapter 2 presents the syntheses of seven new water-soluble beta-CD derivatives (CDs) and describes their ability to shuttle cholesterol between cells and serum lipoproteins. Methyl beta-cyclodextrin (MCD) served as the basis for comparison. Under the conditions used, MCD approximately doubles the efflux of cell cholesterol to serum. Among the tested CDs, two of them display shuttling ability similar to that of MCD. Parts of Chapter 2 have been published in copyrighted journal A (see page vii).;Chapter 3 presents the syntheses of hydrophilic cholesterol-binding molecular imprinted polymers (MIPs). Their steroid-binding properties were analyzed in 2-PrOH by HPLC. The MIPs bound 38 to 50 mumol cholesterol/g, while the corresponding nonimprinted control polymers (containing no cholesteryl acrylate) bound only 6 to 9 mumol cholesterol/g. The sterol-binding selectivity was illustrated with estrone, which was bound by MIPs in the range 5 to 36 mumol/g. Parts of Chapter 3 have been published in copyrighted journal C 2 (see page vii).;Chapter 4 presents the syntheses of a series of new water-soluble beta-CD derivatives and their ability to extract a fatty acid vs. cholesterol. Quaternary ammonium derivatives (CD-N+(Me)2(CH2) nOH OH- and CD-N+(Me)2(CH 2)nNMe2 OH-; n = 1--3) were 400--600 times more effective than beta-CD itself in inducing desorption of palmitic acid from Langmuir monolayers but were completely ineffective hosts for cholesterol. Parts of Chapter 4 are in press (May 2001) in copyrighted journal D (see page vii).;Chapter 5 presents the novel syntheses of 2-dimethylamino-6-(propionyl)naphthalene (prodan), 7-dimethylamino-3-propionyl-1-(methoxy)naphthalene (prodamn), 2-dimethylamino-6-(acryloyl)naphthalene (acrylodan), and prodan-CD. Prodan-CD increases its fluorescence intensity on binding of cholesterol in ethyl acetate.;Chapter 6 presents syntheses of 6-deoxy-6-N-(4-iodophenylamino)-beta-CD and 6,6'-dideoxy-6,6'-di-( N-(4-iodophenylamino))-beta-CD. Molecular modeling indicated that these compounds may bind strongly to cholesterol. The interaction of 6-deoxy-6- N-(4-iodophenylamino)-beta-CD with chenodeoxycholic acid was studied by isothermal calorimetry titration.