【作者】 房丽晶；

【导师】 李裕林；

【作者基本信息】 兰州大学 ， 有机化学， 2007， 博士

【摘要】 本论文以桉烷及杜松烷型倍半萜类天然产物的不对称全合成为主要研究目标，包括以下四部分内容：引言：简要介绍了本论文研究工作的背景、目的和意义。第一部分：桉烷型倍半萜类天然产物的不对称全合成1．以底物控制的Michael加成反应和1，3-二噻烷-2-锂化物与溴代烷的偶联反应为关键反应，经五步、六步反应分别完成了4，5-二氧代-10-表-4，5-开链桉烷的不对称全合成及4，5-二氧代-10-表-4，5-开链桉烷-11-醇的首次不对称全合成。2．针对当前双环倍半萜十氢萘骨架上碳-1位氧代官能团引入的困难，提出了具有我们自己特色的合成策略。以(+)-二氢香芹酮为起始原料，利用底物控制的羟甲基化反应有效地引入了碳-1位氧代官能团，之后经过区域选择性Aldol反应，碱性条件下的Robinson环化，脱水等关键步骤，为化合物1-氧代-10-表莎草酮的合成提供了一种简便有效的新方法，该化合物是合成复杂桉烷类天然产物的重要中间体。并进一步运用该合成策略，完成了天然产物10-表-1β-羟基桉烷-5-烯和10-表-1β，11-二羟基桉烷-5-烯的对映异构体的首次不对称全合成。通过该合成工作，纠正了Becker等人对天然产物10-表-1β-羟基桉烷-5-烯中C4甲基构型的错误推断。第二部分：杜松烷型双环倍半萜类天然产物的不对称全合成1．简要介绍了杜松烷倍半萜化合物的基本结构特征及分类。2．以廉价易得的R-(—)-香芹酮为起始原料，我们设计了以RCM反应、改进的烯丙基二氮烯的重排反应及底物定向的环氧化反应为关键步骤的合成策略，首次完成了Cadinanes型杜松烷化合物4α，5α，10β-Trihydroxycadinane的合成，纠正了Ahmed A．Mahmoud等人对该天然产物结构的错误报道。并在此基础上完成了具有三个羟基、六个手性中心的复杂天然产物4β，5α，10β-Trihydroxycadinane的合成，并确定了其绝对构型。3．仍然以RCM反应和烯丙基二氮烯的重排反应为关键步骤，我们对上述Cadinanes型杜松烷的合成策略进行了扩展，将其应用到Muurolanes型杜松烷的合成当中。完成了两个具有较好生物活性的Muurolanes型双环倍半萜天然产物10α-Hydroxy-4-muurolen-3-one的对映异构体和天然产物10β-Hydroxy-4-muurolen-3-one的首次不对称全合成。第三部分：杜松烷(Cadinenes)天然产物的合成方法研究进展(综述)在这一部分中总结了建立杜松烷(包括Cadinanes、Muurolanes、Amorphanes、Bulgaranes及其他类型)骨架的各种方法。更多还原

【Abstract】 This thesis aims at the studies on the asymmetric total synthesis of natural eudesmane and cadinene sesquiterpenes. It consists of the following four parts:Introduction Part: The background, intention and significance of the research of this thesis were introduced concisely.Part I: The asymmetric total synthesis of eudesmane sesquiterpenes1. The Asymmetric total synthesis of 4,5-Dioxo-10-epi-4,5-seco-γ-eudesmane and 4,5-Dioxo-10-epi-4,5-seco-γ-eudesmanol were achieved starting from (+)-dihydro-carvone through five and six steps, respectively. The key steps in the synthesis include a substrate controlled Michael addition and a coupling reaction of bromide and 2-lithio-2-methyl-1,3-dithiane.2. A novel approach for the enantioselective construction of the naturally occurring C-1 oxygenated 10-epi-eudesmane skeleton starting from (+)-dihydrocarvone was accomplished. This approach relies on a substrate controlled hydromethylation to introduce the C-1 oxygenated group, a regioselective aldol reaction and a alkaline Robinson cyclization to assemble the decalin skeleton. The total synthesis of 1-oxygenated-10-epi-eudesmane, which is the key intermediate for the synthesis of complex eudesmanolides, was achieved. This strategy was further used in the first asymmetric total synthesis of the enantiomers of natural 1β-hydroxy-eudesma-5,11-diene and 1β,11-dihydroxy-5-eudesmene. And the stereochemistry of the C-4 methyl group in natural 1β,11-dihydroxy-5-eudesmene was revised from a toβ.Part II: The asymmetric total synthesis of cadinene sesquiterpenes.1. The basic configuration features and classes of cadinene sesquiterpenes were introduced concisely.2. A highly efficient approach to the synthesis of the trans cadinane skeleton was developed. The approach relies on the straightforward functionization of (R)-carvone to establish three stereocenters, ring closing metathesis (RCM) to produce the decalin ring system, and a modified allylic diazene rearrangement to install the requisite trans-fused cadinane skeleton. Through the first asymmetric total synthesis of 4α,5α,10β-trihydroxycadinane and 4β,5α,10β-trihydroxycadinane, the incorrect structural assignment of the natural cadinane made by Ahmed A. Mahmoud and et al. was revised and the absolute configuration of natural 4β,5α,10β-trihydroxycadinane was established. 3. The efficient synthesis of Muurolane-type cadinenes was studied. Using RCM reaction and allylic diazene rearrangement as the key steps, the first total synthesis of the enantiomer of natural 10α-hydroxy-4-muurolen-3-one and natural 10P-hydroxy-4-muurolen-3-one was accomplished.Part III: ReviewIn this part, some published methods for construction of cadinene-type bicyclic sesquiterpenes were reviewed.更多还原