This thesis describes approaches to the transformation of simple carbohydrates into a polyhydroxylated pyrrolidine and the formation of its glucosides. Chapter one describes the synthesis of the naturally occurring pyrrolidine 2,5-dideoxy-2,5-imino-D-mannitol. Synthesised from di-O-isopropylidene-D-glucose, the key steps are the introduction of nitrogen at C-5 with retention of configuration. Then cyclisation of the nitrogen onto the C-2 position with inversion to form the pyrrolidine ring. Reduction of the aldehyde furnished the polyhydroxylated heterocycle in 3.4% yield over 16 steps. The synthetic compound matched the naturally occurring compound in all respects. Chapter two contains a review of commonly used glycosylation methods. It also describes the glycosylation of di-O-isopropylidene-α-D-glucose as a model system comparing the Koenig-Knorr method to the trichloroacetimidate method using several reaction conditions. Glycosylation of 2,5-dideoxy-2,5-imino-D-mannitol was carried out using the trichloroacetimidate method to synthese all four glucosides. Boron trifluoride etherate and trimethylsilyl trifluoromethanesulphonate were used as catalysts in dichloromethane, diethyl ether and acetonitrile under strictly anhydrous conditions. All four glucosides were prepared 1-O-(αβ-D-glucopyranosyl)-2,5-dideoxy-2,5-imino-D-mannitol and 3-O-(αβ-D-glucopyranosyl)-2,5-dideoxy-2,5-imino-D-mannitol. Biological screening carried out against a wide range of glycosidases and glycosyl transferases indicated that the glucosides showed little inhibition in comparison to 2,5-dideoxy-2,5-imino-D-mannitol. Chapter three describes the isolation and identification of 1-O-(β-D-glucopyranosyl)- 2,5-dideoxy-2,5-imino-D-mannitol from Nephthytis poisonii N.E.Br. a member of the Araceae family found in tropical Africa. Identification was made by comparison with the previously synthesised glucosides of 2,5-dideoxy-2,5-imino-Dmannitol. Investigations of Hyacinthoides non-scriptus (L.) chouard ex Rothm are also discussed. Chapter four describes the synthesis of a diazidolactone that could be used to form a 1,5 disubstituted tetrazole. This would have a second nitrogen functionality in the molecule allowing the possibility of the inclusion of the tetrazole into a peptide sequence. The synthesis was carried out from L-gulono-1,4-lactone. An azido group was introduced selectively at C-2, this unexpectedly occurred with retention of configuration. A second azide was then introduced at C-5, this occurring with the more commonly observed inversion of configuration to afford the 2,5-diazido-2,5-dideoxy-D-manno-1,4-lactone.

In the first part of this study, four new chiral ligands (FAM) were synthesized and used in catalytic amounts in asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides. This method leads to the synthesis of chiral pyrrolidines, which are found in the structure of many biologically active natural compounds and drugs. It was found that using 10 mol% of one of these chiral ligands with different dipolarophiles (dimethyl maleate, dimethyl fumarate, methyl acrylate, tert-butyl acrylate, and Nmethylmaleimide), pyrrolidine derivatives could be synthesized in up to 94% yield and 95% ee. In the second part of the study, the catalytic activity of these chiral ligands were tested with titanium in asymmetric alkynylzinc addition reactions to aldehydes. By this method, chiral propargylic alcohols, which are important precursors for the natural products and pharmaceuticals can be synthesized. Using our catalyst, chiral propargylic alcohols were obtained in up to 96% yield and 98% ee. Although, most of the catalyst systems in the literature worked only with aromatic or aliphatic aldehydes and phenylacetylene, the catalyst system developed in this study worked with four different types of aldehydes (aromatic, aliphatic, heteroaromatic and a,b-unsaturated) and two different aliphatic acetylenes very successfully. Additionally, chiral ligand can be recovered in more than 90% yield and reused without losing its activity.

In this study new twelve phosphorus based chiral ligands were synthesized and characterized. Then the catalytic activity of these chiral ligands was tested with Cu(II) and Ag(I) salts in asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides. This method provides the synthesis of different pyrrolidine derivatives with up to four stereogenic centers. Pyrrolidine derivatives are found in the structure of many biologically active natural compounds and drugs. Therefore the asymmetric synthesis of these compounds is highly important and many groups are involved in this area. As the precursor of the azomethine ylides, N-benzyliden-glycinmethylester, N-(4-methoxy benzyliden)-glycinmethylester, N-(naphthalene-1-ylmethylene)-amino-acetic acid methyl ester, and N-(naphthalen-2-ylmethylene)-amino-acetic acid methyl ester were synthesized and used. As the dipolarophiles, methyl acrylate, dimethyl maleate and N-methyl maleimide were used. Using these imines and dipolarophiles with 6 mol % of one of the P-FAM chiral ligands in the presence of Ag(I) salt, pyrrolidine derivatives were synthesized in up to 95% yield and 89% enantioselectivity. Additionally, chiral ligand was recovered in more than 80% yield and reused without losing its activity.

No / A novel series of 1,4-disubstituted aminoanthraquinones were prepared by ipso-displacement of 1,4-difluoro-5,8-dihydroxyanthraquinones by hydroxylated piperidinyl- or pyrrolidinylalkyl-amino side chains. One aminoanthraquinone (13) was further derivatized to a chloropropyl-amino analogue by treatment with triphenylphosphine-carbon tetrachloride. The compounds were evaluated in the A2780 ovarian cancer cell line and its cisplatin-resistant variants (A2780/ cp70 and A2780/MCP1). The novel anthraquinones were shown to possess up to 5-fold increased potency against the cisplatin-resistant cells compared to the wild-type cells. Growth curve analysis of the hydroxyethylaminoanthraquinone 8 in the osteosarcoma cell line U-2 OS showed that the cell cycle is not frozen, rather there is a late cell cycle arrest consistent with the action of a DNA-damaging topoisomerase II inhibitor. Accumulative apoptotic events, using time lapse photography, indicate that 8 is capable of fully engaging cell cycle arrest pathways in G2 in the absence of early apoptotic commitment. 8 and its chloropropyl analogue 13 retained significant activity against human A2780/cp70 xenografted tumors in mice.