苯酚(醌)与烯烃的不对称[3+2]环化反应: 手性二氢苯并呋喃的合成进展

二氢苯并呋喃结构单元广泛存在于具有良好生物活性和药用价值的天然产物之中, 因而引起了有机合成化学家和药物化学家们的关注. 针对该结构单元所包含的C2和C3邻二立体中心的对映选择性构建, 也是目前有机合成方法学研究的挑战性问题之一. 在众多解决方案中, 以苯酚(醌)与烯烃为底物, 具体采用催化不对称和手性辅剂诱导的[3+2]环化两种方式, 可以构建具有光学活性的二氢苯并呋喃结构单元. 本综述将不同类型的手性催化剂和手性辅剂进行分类梳理, 介绍了近年来不对称[3+2]环化反应的发展, 并重点剖析其中涉及的立体选择性控制. 同时, 简要介绍了该关键方法在二氢苯并呋喃天然产物合成中的应用. 为了启发更加高效和普适性的新催化体系出现, 最后总结和展望了不对称[3+2]环化反应的发展趋势.     

胶束催化体系中的对映选择性环醚化反应

The enantioselective cycloetherification of substituted keto phenols into their corresponding dihydrobenzofuran derivatives was carried out using hydrogen peroxide and chiral quaternary ammonium iodide in micellar media. This approach increased the conversion rate of cycloetherification and also widened the scope of this particular reaction for various substituted keto phenols with electron withdrawing as well as electron donating functionalities. The use of a surfactant in the cycloetherification reaction ...     

8-5’新木脂素类化合物的合成方法研究

对羟基桂皮酸甲酯和阿魏酸甲酯分别在氧化银催化下发生自由基仿生氧化偶联反应, 合成得苯并二氢呋喃环结构化合物1, 1经甲基化反应得2. 1a和1和2分别在无水碳酸钾、10%氢氧化钠水溶液等不同的碱性条件下进行反应, 获得了11个苯并二氢呋喃环开环产物, 即8-5’新木脂素类化合物3a～9b, 实现了由苯并二氢呋喃新木脂素向8-5’新木脂素的转变, 也为合成芪类化合物提供了一种新方法. C-8位上的吸电子基团如酯基的影响使苯并二氢呋喃环易在碱性条件下开环形成8-5’新木脂素类化合物．所合成化合物的结构由MS, IR, 1H NMR和13C NMR进行了表征.     

新型苯并二氢呋喃合二酮酸类化合物的合成及其与整合酶分子对接研究

以阿魏酸甲酯为原料,通过氧化偶联构建2-芳基苯并二氢呋喃骨架,再经傅克酰基化和酯缩合反应依次制得(E)-3-［2-(4-羟基-3-甲氧基-5-乙酰基)苯基-3-甲氧羰基-7-甲氧基-2,3-二氢苯［b］并呋喃-5-基］丙烯酸甲酯（3）和(E)-3-［2-(4-羟基-3-甲氧基-5-甲氧羰基乙酰基)苯基-3-甲氧羰基-7-甲氧基-2,3二氢苯并［b］呋喃-5-基］丙烯酸甲酯（4）; 4经水解反应合成3-【2-羟基-3-甲氧基-5-｛5-［2-（甲氧基羰基）乙烯基］-7-甲氧基-3-甲氧羰基-2,3-二氢苯并［b］呋喃-2-｝基】苯基-3-氧丙酸（5）,化合物3~5未见文献报道,其结构经¹H NMR, ¹³C NMR和MS(ESI)表征。采用分子对接软件Autodock vina对化合物2~5与HIV-1整合酶核心部位高度同源的PFV IN（PDB: 3L2V）进行对接,计算结果显示该类化合物能与整合酶形成稳定的复合物,具有1,3-二酮基团的化合物3, 4和5能与整合酶中金属离子产生螯合作用,其中化合物5的结合作用最强。     

A new dihydrobenzofuran lignan and potential α-glucosidase inhibitory activity of isolated compounds from Mitrephora teysmannii

A new dihydrobenzofuran lignan, (2R,3S)-2-(3′,4′-dimethoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-2,3-dihydrobenzofuran-3-methyl acetate, named as mitredrusin (1), was isolated from the leaves of Mitrephora teysmannii (Annonaceae) together with 12 known compounds including a related dihydrobenzofuran lignan: (?)-3′,4-di-O-methylcedrusin (2), four polyacetylenic acids: 13(E)-octadecene-9,11-diynoic acid (3), 13(E),17-octadecadiene-9,11-diynoic acid (4), octadeca-9,11,13-triynoic acid (5) and octadeca-17-en-9,11,13-triynoic acid (6), five lignans: (?)-eudesmin (7), (?)-epieudesmin (8), (?)-phillygenin (9), magnone A (10) and forsythialan B (11) and two megastigmans: (3S,5R,6S,7E,9R)-7-megastigmene-3,6,9-triol (12) and annoionol A (13). The chemical structures of these compounds were established on the basis of their 1-D and 2-D NMR spectroscopic data. All compounds were evaluated for their α-glucosidase inhibitory activity. Among these isolates, polyacetylenic acids 3 and 4 showed more than 20-fold much higher activity compared with that of the antidiabetic drug acarbose.     

Copper‐Catalyzed Intramolecular Desymmetric Aryl CO Coupling for the Enantioselective Construction of Chiral Dihydrobenzofurans and Dihydrobenzopyrans

O‐Heterocyclic structures such as 2,3‐dihydrobenzofurans are key motifs in many natural compounds and pharmaceuticals. Enantioselective formation of chiral dihydrobenzofurans and analogues was achieved through a copper‐catalyzed desymmetrization strategy with a chiral cyclic 1,2‐diamine. A broad range of substrates are compatible with this Cu^I‐diamine catalytic system and afford the desired coupling products with chiral tertiary or quaternary carbon centers in high yields and good to excellent enantioselectivities under mild conditions.     

Gas‐phase fragmentation reactions of protonated benzofuran‐ and dihydrobenzofuran‐type neolignans investigated by accurate‐mass electrospray ionization tandem mass spectrometry

We have investigated gas‐phase fragmentation reactions of protonated benzofuran neolignans (BNs) and dihydrobenzofuran neolignans (DBNs) by accurate‐mass electrospray ionization tandem and multiple‐stage (MSⁿ) mass spectrometry combined with thermochemical data estimated by Computational Chemistry. Most of the protonated compounds fragment into product ions B ([M + H–MeOH]⁺), C ([ B –MeOH]⁺), D ([ C –CO]⁺), and E ([ D –CO]⁺) upon collision‐induced dissociation (CID). However, we identified a series of diagnostic ions and associated them with specific structural features. In the case of compounds displaying an acetoxy group at C‐4, product ion C produces diagnostic ions K ([ C –C₂H₂O]⁺), L ([ K –CO]⁺), and P ([ L –CO]⁺). Formation of product ions H ([ D –H₂O]⁺) and M ([ H –CO]⁺) is associated with the hydroxyl group at C‐3 and C‐3′, whereas product ions N ([ D –MeOH]⁺) and O ([ N –MeOH]⁺) indicate a methoxyl group at the same positions. Finally, product ions F ([ A –C₂H₂O]⁺), Q ([ A –C₃H₆O₂]⁺), I ([ A –C₆H₆O]⁺), and J ([ I –MeOH]⁺) for DBNs and product ion G ([ B –C₂H₂O]⁺) for BNs diagnose a saturated bond between C‐7′ and C‐8′. We used these structure‐fragmentation relationships in combination with deuterium exchange experiments, MSⁿ data, and Computational Chemistry to elucidate the gas‐phase fragmentation pathways of these compounds. These results could help to elucidate DBN and BN metabolites in in vivo and in vitro studies on the basis of electrospray ionization ESI‐CID‐MS/MS data only.     

Stereoselective cyclization of stilbene derived carbocations

Cyclodimerization of 2,6-dimethoxy-4-methylstilbene under acidic conditions affords the rotationally restricted 1,3-bis-(2,6-dimethoxy-4-methylphenyl)-2-phenyl-1,2,3,4-tetrahydronaphthalene. Nucleophilic addition of this stilbene to 1,4-benzoquinone and maleic anhydride, respectively, followed by an intramolecular cyclization yields dihydrobenzofuran derivatives and a trisubstituted butanolide, respectively. These stereoselective cyclizations involving stilbene derived carbocations apparently biomimic the cyclization of naturally occurring stilbenes during oxidative oligomerization.