Cyclic amino alcohol derived asymmetric methodologies and design and synthesis of HIV protease inhibitors (Immune deficiency)

Design and development of new chiral auxiliaries for asymmetric reactions are described in part one. New chiral templates which are not derived from natural amino acids are developed because this unnatural template may offer opportunities to manipulate its structural properties and conformational rigidities. One of the new chiral auxiliaries developed was (4R,5 S)-hexahydro-cyclopentanoxazolidin-2-one which exhibited excellent diastereofacial selectivities (>99% de) and good isolated yields (65--80%) in asymmetric syn-aldol reactions.; This new chiral auxiliary was also investigated by asymmetric Diels-Alder reactions, and it is described in chapter two. Diels-Alder reaction of the dienophiles with various optically active oxazolidinones was resulted in good diastereoselectivity (91:9) and isolated yield (88%). Additional studies concerning the ring size of this new chiral auxiliary were described.; Chapter three describes asymmetric catalysis in Diels-Alder reactions. A cis-1-aminoindan-2-ol derived bis(oxazoline) was synthesized as a ligand for asymmetric catalysis. Development of a catalytic system which is not sensitive to air and moisture is described. Among various metal perchlorates, inexpensive commercially available CU(C104)2-6H2O exhibited the best enantioselectivities (98% ee).; Design, synthesis and evaluation of inhibitors of the HIV-1 protease enzyme are described in part two. Wild type HIV-1 protease was expressed and purified, and an assay protocol was developed using this protease and anthranilyl fluorogenic substrate against different inhibitors.; For designing potent HIV-1 inhibitors, we have systematically modified a potent inhibitor developed in our laboratory. To understand the ligand binding site interactions in the active site of HIV-1 protease, the hydrophobic group from the hydroxyethylamine isostere was removed. We then investigated the possibility of filling the pocket by attaching substituents in P2-ligands. Finally, a new class of macrocyclic compounds were designed to reach the hydrophobic pocket from the P1 to P2 sites.