Development of new synthetic routes to chiral intermediates and synthesis, characterization of novel membrane based advanced materials.

摘要

The main objective of this dissertation is to develop chiral technology for the synthesis of chiral building blocks especially for use in the pharmaceutical and advanced material industries. The two major thrusts are carbohydrate and amino acid based asymmetric synthesis and the design and synthesis of novel, stabilized, membrane lipid based systems which have potential applications in the fabrication of molecular photonic-electronic devices, biosensors, and drug delivery systems.; There are two parts in this dissertation. The first part (chapters 2, 3) describe about the development of new asymmetric synthetic routes to chiral building blocks and chiral drugs for the pharmaceutical industry. This includes the development of new synthetic routes to chiral 3-carbon synthons which are key building blocks for many important compounds such as antiviral drugs, cardiovasicular agents, chiral membrane lipids and other glycerol derivatives. It is also describes the development of new asymmetric synthesis of important drugs such as L-carnitine, R- g -amino- b -hydroxybutyrate (GABOB) and S-beta blockers. New synthetic routes to chiral cis-1-amino-2-indanols, key building block for HIV protease inhibitors and important catalysts in asymmetric synthesis are also demonstrated. These new routes have significant advantages over the existing routes, giving high yields and high optical purity and by simple processes that are highly efficient and applicable to industry. The chirality of the products are conserved from the chiral starting carbohydrate and amino acids.; The second part of the dissertation (chapters 5, 6 & 7) is about the design, synthesis and properties of new advanced materials based on membrane mimics. These include stabilized phospholipid analogs and liposomes, chiral multifunctional self assembled 2-dimensional polydiacetylene containing systems, 2-dimensional conducting polyamide conducting thin films and other advanced materials. A tail-to-tail dimer of phosphatidyl ethanolamine was prepared and shown to readily form very uniformly flat self assembled lamellar supramolecular arrays and liposome that are stable at temperatures up to 80°C. This extremely stable and readily functionalizable dimeric phospholipid has potential uses in the fabrication of biomaterials, stable membrane models and liposome drug delivery systems. In chapter 6, two new, very accessible, chiral, self-assembling phospholipid analogs containing diacetylenic units in the middle of their acyl chains were prepared by very simple and highly efficient routes. They formed very uniform, extremely flat, thin films which are readily polymerized to give extensively conjugated systems which absorbed well out into the near infrared region unlike typical polydiacetylenes. The results indicate that this is an excellent approach for preparing ordered polydiacetylene systems for use in designing advanced materials. The last chapter introduces a new approach for obtaining long range order and perfect alignment of long chain polydiacetylene by anchoring them along a polymer backbone.