合成(E)-5-(2-Radioiodovinyl)arabinosyl Uridine類似物作為皰疹病毒第一型胸腺嘧啶激脢基因探針之研究

Abstract

Abstract Cancer gene therapy has become a promising approach for treatment of cancer. For achieving the optimized therapeutic effect, a probe which may localize the gene expression, should be developed. By employing nuclear medical instrument such as Positron Emission Tomography and Single Photon Emission Computer Tomography, the noninvasive imaging may be realized. HSV-TK was one of the most used reporter gene and radionuclide was the responsible tracer. Recently, various radionuclides have been prepared. Among them, fluorine, bromine and iodine are frequently used. Organostannan has been widely used in iododestannylation reaction. To our purpose, we are focusing on the preparation of tributyl stannyl nucleoside and its application to radiohalogenation. The commercial uridine was treated with base to provide 2,2’-anhydro uridine 1 with high melting point and no indication of sugar by staining with p-anisaldehyde. Without chromatographic purification, product 1 could be obtained in high yield through washing with cold MeOH. Aarbinosyl uridine 2 could be obtained by ring opening using trace TFA. Following protection by acetylation, iodine could be introduced on C-5 through electrophilic iodination. Iodo group could be replaced by trimethylsilyl ethynyl group in 80% yield. Removal of silyl group was affected by KF. Tributylstannylation was performed under addition of HSnBu3 and yield was 80%. The steric hindrance might account for the unavailability of (Z)-product. Following the removal of acetyl groups with base, a yield of 80% of [125I] (E)-iodovinyl arabinosyluridine could be identified in HPLC chromatogram.