几种生物活性分子的合成研究-生物学专业论文.docxVIP

浙江大学博士出站报告摘 浙江大学博士出站报告 摘 要 本文介绍了在站期间的部分研究工作 主要包括三部分：(1)非肽类血管紧 张素II受体拮抗剂——坎地沙坦酯的合成 (2)Corey内酯的不对称合成；(3)自 旋标记柔红霉素衍生物的合成。 第一部分概述了非肽类血管紧张素II受体拮抗剂的研究进展，在对文献报道 的合成路线加以改进的基础上，以3．硝基邻苯二甲酸为起始原料，经过酯化、 Cufius重排、烷基化、还原、环合、取代等13步反应合成了抗高血压药物坎地 沙坦酯，总收率为15，18％，高于文献报道收率(7曲％)。 第二部分概述了前列腺素及Corey内酯的合成方法及研究进展．以环戊二烯 二聚体为起始原料，经(．)．di．3．pinanyl．borane不对称还原、关环、烯烃不对称双 官能化、保护、酯化等10步反应合成了Corey内酯，全程收率10％。 第三部分对葸环类抗肿瘤抗生素及氮氧自由基在自旋标记抗癌药物中的作 用机理进行简要概述。在以往的工作基础上，设计了一条合成自旋标记4’．圣}Ⅳ- 三氟乙酰柔红霉素衍生物的简便路线，其关键步骤是C9位羟基保护及羧酸．DBU 体系与三氟磺酸酯的亲核取代反应。 浙江大学博士出站报告Abstract 浙江大学博士出站报告 Abstract This Thesis comprised ofthree parts：(1)the synthesis ofnonpetide AII receptor antagonists Candesartan；(2)the asymmetry synthesis of Corey lactone；(3)the synthesis of spin-labeled analogues of daunorubicine． The developments of nonpetide A II receptor antagonists were introduced in the first part．On the basis of the introduction，Candesartan，a novel nonpetide A II receptor matagonist．was synthesized by a improved protocol with 3-nitrophthalic acid as starting materials in 1 5-1 8％overall yield．The method was composed of H+-resin—catalyzed esterification，improved Curtius rearrangement，alkalization with CsC03，transfer·hydrolization reduction and cyclization with tetraalkoxymethane and acetic acid． In the second part，the syntheses method of Corey lactone and the research developments of PGF were introduced frstly．Corey lactone was synthesized by a 10 steps protocol with cyclopentadiene as starting materials in 1 0％overall yield．The key steps were：(1)asymmetry reduction with(一)-di-3-pinanyl·borane；(2)acid or base catalyzed lactonization；(3)asymmetry reaction、^，ith HOAc and HCHO of Mkene． In the end，the lately developments of anthracycline antibiotics and the action model of spin—labeled medicine molecule were briefly introduced．In addition to that， the spin labeled 4-Epi-N-trifuoroacetyIdaunomycin derivatives ZDM7-10 were conveniently synthesized from N-trifuoroacetyldaunomycin in middle yield．The key steps were the protection of triflte