Synthesis Of Thyromimetic GC-1 And 2', 3'-spiro Nucleosides Intermediates

The thesis is divided into two parts, dealing with the synthesis of GC-1, which belongs to a member of a new class of thyromimetic compounds that have more potency and better selectivity toward TR-β　nuclear receptor than that of natural thyroxine and the synthesis of 2′, 3′-spiro nucleosides intermediates. The final products were fully characterized by HPLC-MS, 1H NMR.In the first part, a nine-step synthetic route to GC-1 has been developed. The synthesis started from commercially available 2-isopropylphenol by the sequence of reactions including the bromination of reactive aromatic rings, aldehyde addition, hydrogenation of alcohol and mono-alkylation of phenol. In the process of hydrogenation, we changed the solvent and successfully sovle the problem of -OEt substitution at methylene position. In addition, we reduced the amount of cesium carbonate from 5eqv to 1.5eqv, and consumedly cut down the costs of the reaction.In the second part, efficient and high-yielding synthetic routes were evaluated for the preparation of 2′, 3′-spiro nucleosides intermediates: 1-(5′-O-trityl-3′-deoxy-3′-azido-β-D-arabinofuranosyl) uracil, 1-(5′-O- trityl-3′-deoxy-3′-azido-β-D-xylofuranosyl) uracil and 1-{5′-O-(TBS)-3′- deoxy-3′-[N,N-(o-bromobenzylallyl)amino]}thymine, which lay the foundation for further study of 1,5-radical translocation reaction.