异海绵烷二萜Kravanhins A-C的全合成及石松生物碱 Annotinolide B的合成研究
中文摘要
本论文叙述了近年来光诱导的烯烃[2+2]环加成反应，并针对异海绵烷二萜kravanhins A-C与石松生物碱annotinolide B开展了合成研究。该论文共包括三章：第一章光诱导的烯烃[2+2]环加成反应（综述） 简要综述了近20年内烯烃通过紫外光直接激发或光敏化作用发生[2+2]光环加成反应的进展。本综述按照受激发的烯烃的共轭类型，对非共轭烯烃、芳基共轭的烯烃、α,β-不饱和酮以及α,β-不饱和羧酸衍生物分别进行讨论。
第二章异海绵烷二萜Kravanhins A-C的全合成
简要介绍了海绵烷二萜的分离与合成研究。我们以结构新颖的异海绵烷四环二萜kravanhins A-C作为合成目标。第一代合成以13步6.2% 的总产率完成了(-)-kravanhin B的首次不对称全合成。关键步骤是用分子内aldol环化反应构筑了trans-anti-cis三环骨架并用酸催化的脱水反应串联烯烃异构化反应构筑了丁烯内酯环。第二代合成是以仿生的策略对(-)-kravanhins A和C进行全合成。我们提出了半日花烷二萜转化成异海绵烷二萜的生源假说，并以此对(-)-kravanhins A和C 进行了反合成分析。整个合成先通过汇聚的
往复式喷漆机
策略合成了呋喃型的半日花烷二萜衍生物，再通过1O2参与的光氧化反应得到γ-羟基丁烯内酯型半日花烷二萜衍生物。然后，用γ-羟基丁烯内酯通过关键的aldol环化串联内酯化反应合成了异海绵烷二萜(-)-kravanhin C，最后通过区域选择性与立体选择性的还原反应得到了(-)-kravanhin A。这部分工作对探索自然界中萜类的生源转化具有参考意义。
第三章石松生物碱Annotinolide B的合成研究
缀花草坪简要介绍了石松生物碱lycopodine的分离以及一部分代表性的合成研究。我们以结构新颖的五环石松生物碱annotinolide B作为合成目标。关键反应是通过aldol缩合反应构筑Ａ环，并通过光诱导的烯烃[2+2]环加成反应合成四元环与内酯环。目前，我们已经用aldol缩合构筑了Ａ环，实现了ABC三环骨架的构筑。这部分工作正在进行中。
关键词：羟醛反应，仿生合成，天然产物，一锅反应，全合成
Total Syntheses of Isospongian Diterpenoids Kravanhins A-C and Synthetic Studies toward Lycopodium Alkaloid
Annotinolide B
Abstract
The thesis describes recent advances of olefin [2+2] photocycloaddition reactions and efforts toward total syntheses of isospongian diterpenoids kravanhins A-C and Lycopodium alkaloid annotinolide B.
全部视频列播放表本站Chapter 1. Olefin [2+2] Photocycloaddition Reactions (Review)
The review aims to discuss advances in the synthesis of cyclobutanes by olefin [2+2] photocycloaddition reactions which occur by direct excitation or sensitization in the last 20 years. According to the photochemically excited olefin, nonconjugated alkenes, arene-conjugated alkenes, α,β-unsaturated ketones, and α,β-unsaturated carboxylic acid derivatives were discussed in individual subsections.
Chapter 2. Total Syntheses of Isospongian Diterpenoids Kravanhins A-C
A brief introduction of the background for the isolation and syntheses of spongian diterpenoids is provided. Theree novel tetracyclic isospongian diterpenoids kravanhins A-C represent attractive targets for our group. In the first study, we report the first asymmetric total synthesis of (-)-kravanhin
B (13 steps, 6.2% overall yield). The synthesis features an intramolecular aldol cyclization to construct the desired trans-anti-cis fused tricyclic ring skeleton and an acid catalyzed dehydration an
d olefin isomerization to install the γ-butenolide ring. In the second study, we report the first asymmetric bioinspired total syntheses of kravanhins A and C. We proposed a plausible biosynthetic pathway for isospongian diterpenoids from labdane diterpenes, and then retrosynthetic analysis toward (-)-kravanhins A and
C was described. A convergent pathway was used to construct the furanolabdane derivative, followed by a photooxidation with singlet oxygen gave the required γ-hydroxybutenolide labdane derivative. Then (-)-kravanhin C was obtained through a one-pot sequential aldol cyclization and lactonization. At last stage, the synthesis of (-)-kravanhin A was completing via a regioselective and stereoselective reduction. This work is worthy for searching biosynthetic pathway for terpenoids.
Chapter 3. Synthetic Studies toward Lycopodium Alkaloid Annotinolide B
A brief introduction of the isolation and representative syntheses of Lycopodium alkaloid lycopodine is provided. The novel Lycopodium alkaloid annotinolide
B represents attractive target for our group. The retrosynthetic analysis features an aldol condensation to construct A-ring and an olefin [2+2] photocycloaddition reaction to construct cyclobutane ring and lactone ring. At present, an intramolecular aldol condensation has been used to
construct the desired AB
C tricyclic ring skeleton. This synthetic study is ongoing.
Key words: aldol reaction, biosynthesis, natural products, one-pot reactions, total synthesis
缩略语简表
ac acetone / 丙酮
Ac acetyl / 乙酰基
AIBN azodiisobutyronitrile / 偶氮二异
9-BBN 9-borabicyclo[3.3.1]nonane / 9-硼双环(3,3,1)-壬烷
Bn benzyl / 苄基
Boc tert-butyloxy carbonyl / 叔丁氧羰基
Bu butyl / 丁基
t-Bu tert-butyl / 叔丁基
m-CPBA meta-chloroperbenzoic acid / 间氯过氧苯甲酸
DAST diethylaminosulfur trifluoride / 二乙胺基三氟化硫DCM dichloromethane / 二氯甲烷
DMAP 4-N,N-dimethylaminopyridine / 4-N,N-二甲氨基吡啶DMF N,N-dimethylformamide / N,N-二甲基甲酰胺
DMP Dess-Martin periodinane / 戴斯-马丁氧化剂
DMSO dimethylsulfoxide / 二甲基亚砜
DMTSF dimethyl(methylthio)sulfonium tetrafluoroborate
Et ethyl / 乙基
HMPA hexamethylphosphoric acid triamide / 六甲基磷酰三胺ISC intersystem crossing / 系间窜越
LAH lithium aluminum hydride / 氢化铝锂
LDA lithium diisopropylamide / 二异丙基胺基锂
播放路
LED light emitting diodes / 发光二极管
Me methyl / 甲基
MEM (2-methoxyethoxy)methyl / (2-甲氧基乙氧基)甲基
mp melting point / 熔点
Ms methanesulfonyl / 甲磺酰基
NMO N-methylmorpholine oxide / N-甲基吗啉氧化物
毛刷制作PCC pyridinium chlorochromate / 氯铬酸吡啶盐
Ph phenyl / 苯基
PMP para-methoxyphenyl / 对甲氧基苯基
PPTS pyridinium p-toluenesulfonate / 对甲苯磺酸吡啶盐
i-Pr isopropyl / 异丙基
Py pyridine / 吡啶
quant. quantitative / 定量的
RCM ring-closing metathesis / 关环复分解反应
TBAF tetrabutylammonium fluoride / 四丁基氟化铵
TBAI tetra-n-butylammonium iodide / 四丁基碘化铵
人机对弈TBS tert-butyldimethylsilyl / 叔丁基二甲基硅基
Triton B benzyl(trimethyl)azanium hydroxide / 苄基三甲基氢氧化铵Ts p-toluenesulfonyl / 对甲苯磺酰基
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