恶唑酮并六元杂环化合物的合成方法学研究-药学专业论文.docx

摘 要 恶唑酮并六元杂环化合物在天然产物全合成及药物化学研究领域具有重要的 作用。这一结构不仅存在于许多药物分子，而且可以用于天然生物碱的合成。本 文发现了恶唑酮经 Aza-Prins 反应制备恶唑酮并六元杂环化合物的方法，即用路易 斯酸三氟化硼乙醚作为催化剂，催化带有不同取代基团的恶唑酮进行环化反应， 得到一系列恶唑酮并六元杂环化合物；同时对反应条件进行了系统的研究和优化， 得出最佳反应条件，提出并验证了可能的机理。本课题共合成了三类 22 个不同的 恶唑酮并六元杂环化合物；提出了 8 个反应受阻的情况，并利用密度泛函理论计 算给出了反应受阻的原因。本课题发展了以 Aza-Prins 反应作为关键步骤制备恶唑 酮并六元杂环化合物的方法，产率高（产率最高达到 94%），区域选择性及非对映 选择性好，当恶唑酮并六元杂环结构的 2, 3 碳位被取代时，区域选择性最佳，且 产物的 dr 值均大于 99/1。 关键词：恶唑酮并六元杂环化合物，环化反应，Aza-Prins 反应 ABSTRACT 6-Membered-ring fused Oxazolidones play significant role in the total synthesis of natural products and drugs. Their structural skeleton can be used as key intermediate for the synthesis of a number of natural alkaloids. In this thesis, Aza-Prins cyclization reaction catalyzed by Lewis acid BF3?Et2O for synthesis of different substituted 6-membered-ring fused oxazolidones was discovered. The best reaction condition was found by optimizing the different reaction parameters. With the optimized reaction conditions, 22 different 6-membered-ring fused oxazolidones were synthesised. Based on experimental studies, a possible mechanism of the reaction was proposed. Density Functional Theory justified the failed cyclization for 8 examples. The products were obtained in good yields (yield up to 94%), very high regioselectivity and diastereo selectivity, the best regioselectivity appeared in 2, 3-carbon substituted 6-membered -ring fused oxazolidones, their dr values were more than 99/1. Keywords: 6-Membered-Ring fused Oxazolidones, Cyclization, Aza-Prins reaction 目 录 中文摘要..........................................................................................................................................I 英文摘要....................................................................................................................................... III 英文缩略词 ............................................................................................................................... VII 1 绪 论...........................................