Threo-(±)-开环异落叶松脂醇二阿魏酸酯的全合成

报道了双木脂素threo-(±)-开环异落叶松脂醇二阿魏酸酯的全合成.以香草醛为原料,经过两步Sto-bbe反应构建木脂素骨架,然后再用LiAlH4还原、加氢后,产物经柱层析分离,得到2个异构体meso-和threo-(±)-开环落叶松脂素;根据其NMR,IR和HRMS等谱图确认发现,极性较小的产物threo-(±)-开环落叶松脂素为合成的关键中间体.threo-(±)-开环落叶松脂素与甲氧甲基(MOM)保护的阿魏酸缩合得到目标产物threo-(±)-开环异落叶松脂醇二阿魏酸酯.合成采用汇聚法,经11步,以约8%的总产率得到了目标产物.该合成方法具有原料价廉易得及操作简便的优点,并具有一定的实用价值.     

倍半木脂素threo-(±)-3,4-二香草基四氢呋喃阿魏酸酯的全合成

报道了一条合成天然产物3,4-二香草基四氢呋喃阿魏酸酯的方法.以香草醛为原料,经过两步Stobbe反应构建木脂素骨架,然后再加氢、LiAlH4还原,产物经柱层析分离后得到两个异构体meso-和threo-(±)-开环落叶松脂素;它们分别与TsCl作用,发生分子内反应得到关键的四氢呋喃木脂素中间体meso-和threo-(±)-shonanin;最后,分别与MOM保护的阿魏酸缩合得到倍半木脂素threo-(±)-3,4-二香草基四氢呋喃阿魏酸酯和衍生物erythro-(±)-3,4-二香草基四氢呋喃阿魏酸酯.合成采用汇聚法,经13步,以约8%～9%的总产率得到了目标产物.     

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.     

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2．1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．     

(-)-(1R,2S)-肉豆蔻木脂素的不对称合成

报道了天然产物(-)-肉豆蔻木脂素的全合成. 以香草醛为起始原料, 经Wittig反应、LiAlH₄还原和Sharplass不对称双羟化等反应构建了苏式结构的中间体; 以焦性没食子酸为原料, 经Claisen重排反应制得另一种苯丙素片段; 2个中间体通过Mitsunobu反应, 缩合并使构型翻转, 得到赤式-(-)-肉豆蔻木脂素. 为赤式8-O-4′新木脂素的合成提供了一种新方法.     

从D-甘露糖醇合成(2S, 3R)-鞘氨醇

以D-甘露糖醇为原料, 在制得了(2E)-4, 5-氧异亚丙基戊烯酸酯(5)以后,经不对称双羟基化反应、环硫酸酯化和叠氮化钠区域选择性开环等12步反应以7.7%的总产率合成了标题化合物的2, 3-二苯甲酰产物, 由此为鞘氨醇和神经鞘脂类化合物的合成开辟了又一新的途径。     

螺环倍半萜(±)-茅苍术醇和(±)-沉香螺醇的改进合成

以2,4-二氧代戊酸甲酯(1)和1,5-二甲基-6-亚甲基环己烯(2)为原料,通过[2+2]光环加成和retro-Benzilicacid重排,合成了具有螺[4,5]癸烷结构的岩兰烷基本碳架的化合物3.用锌粉选择还原五元环上碳碳双键得螺环二酮(4),对环外羰基实施保护并将环上酮基转化为亚甲基得到重要的合成前体6,经与甲基溴化镁的格氏反应生成混合的标题化合物.利用羟基和异氰酸苯酯的反应生成一对N-苯基氨基甲酸酯异构体(12),二者分离后经四氢铝锂还原,完成了螺环倍半萜(±)-茅苍术醇和(±)-沉香螺醇的全合成.     

木脂素类化合物的全合成研究

综述了本研究小组近几年在木脂素全合成研究中取得的新进展。主要包括三部分：通过β-酮酸酯偶联反应来合成去甲二氢愈创木酸及多种其它类型木脂素;通过氧化银偶联和DDQ合环首次合成黄酮木脂素(±)-Sinaiticin;通过Sharpless不对称双羟化为关键步骤首次手性合成1,4-苯并二氧六环类新木脂素。     

二苯丁脂类木脂素及衍生物的合成和抗肿瘤活性研究

以胡椒醛和藜芦醛为原料, 通过Stobbe缩合和烷基化反应构建木脂素骨架、手性试剂拆分, 经官能团转换后, 得到了10个二苯丁脂类木脂素, 其中4个为天然产物. 合成得到的化合物进行了抗肿瘤活性测定, 结果表明, 部分化合物物具有较强的抑制乳腺癌细胞活性.     

超声波辐射下异阿魏酸对氯苯酚酯的一步合成

室温超声辐射下,4-二甲氨基吡啶(DMAP)作催化剂,二环己基碳二亚胺(DCC)作脱水剂,不需保护异阿魏酸分子中的羟基,异阿魏酸和对氯苯酚的一步反应直接合成了异阿魏酸对氯苯酚酯。在n(异阿魏酸):n(对氯苯酚):n(DCC):n(DMAP)=1:1.2:1.2:0.1混合时,室温超声反应2.5h,得产率76.2%。目标化合物的结构经元素分析、1HNMR和IR测试技术得到确证。缩短了反应时间,提高了产率。     

Synthesis of vinca alkaloids and related compounds. Part 102: Simple synthesis and ring transformation of (±)-minovincine. First synthesis of (±)-vincaminine

A molecule with an indole skeleton, containing a latent acrylic ester function—acting as a diene—readily reacted with benzoic acid (4-bromomethylene-5-oxo)hexyl ester that had been built up from pentane-2,4-dione. Dehydration of the enamine and subsequent [4+2] cycloaddition supplied epimers having the d-secoaspidospermane skeleton. These compounds directly or after epimerization gave (±)-minovincine. Oxidative ring transformation of (±)-minovincine under different conditions led to (±)-16-acetyl-16-deethylapovincamine and (±)-vincaminine.     

Concise total syntheses of (±)isopaucifloral F, (±)quadrangularin A, and (±)pallidol

Concise total syntheses of (±)isopaucifloral F, (±)quadrangularin A, and (±)pallidol, starting from commercially available 3,5-dimethoxybenzoic acid, have been achieved by a sequential process. The overall synthetic strategy involves Nazarov cyclization, Ramberg-Backlund olefination, and Friedel-Crafts alkylation.     

Synthesis of (±)-6-oxa-3-azabicyclo[3.1.1]heptan-2-thione: a potential synthon for the preparation of novel heteroaryl-annulated bicyclic morpholines

The novel bridged bicyclic morpholinethione (±)-6-oxa-3-azabicyclo[3.1.1]heptan-2-thione (9) has been prepared in six steps. This conformationally restricted morpholinethione was prepared stereoselectively using straightforward chemistry and inexpensive starting materials. The key oxetane ring was formed via an intramolecular alkylation reaction.     

Synthesis of (±)-coerulescine and a formal synthesis of (±)-horsfiline

A straightforward synthesis of (±)-coerulescine and (±)-horsfiline has been established from 3-formyl-3-phenylpyrrolidine employing 4-hydroxypiperidine as the starting material. There are two remarkable steps for the synthesis of (±)-coerulescine and (±)-horsfiline. One is the rapid access to produce 3-formyl-3-phenylpyrrolidine by Lewis acid-catalyzed rearrangement of 3,4-dihydroxy-4-phenylpiperidine. The other key step is an intramolecular electrophilic cyclization from 3-benzylcarbamoyl-3-phenylpyrrolidine to the 3,3-spirocyclic 2-oxindole ring skeleton.     

First synthesis of (±)-bis-homosarkomycin ethyl ester

A five step synthesis of (±)-bis-homosarkomycin ethyl ester 6 has been achieved starting from commercially available ethyl phosphonoacetate and ethyl 5-bromovalerate. The successful synthetic approach to 6 uses α-methylene pimelate 3 as a key intermediate.     

Cyclopropylcarbinyl radicals as three-carbon insertion units: easy synthesis of C-15 macrocyclic ketones by three-carbon ring expansion

Thermal isomerization of cyclic 3-cyclopropyl ketones under FVP conditions at 620 °C provides a new and convenient route to δ,ε-unsaturated cycloalkanones. The synthetic potential of this novel three-carbon ring expansion has been demonstrated by the synthesis of (±)-muscone from inexpensive C-12 starting material.     

A variation of the Pictet-Spengler reaction via a sequential reduction-cyclization reaction of N-acylcarbamates: synthesis of 1-substituted tetrahydroisoquinoline derivatives

A new variation of the Pictet-Spengler reaction for the synthesis of 1-substituted tetrahydroisoquinoline derivatives has been developed. The reaction employs the reduction of N-acylcarbamates by DIBAL-H followed by simultaneous cyclization mediated by BF₃·OEt₂. The synthetic potential of this method has been illustrated by the synthesis of the tetrahydroisoquinoline alkaloids, (±)-xylopinine, (±)-laudanosine, (±)-8-oxo-O-methylbharatamine, and (±)-isoindoloisoquinolone.     

Chemoenzymatic preparation of optically active 4-aryl-5-carboxy-6-methyl-3,4-dihydro-2(1H)-pyridone derivatives

A series of racemic 4-aryl-5-(tert-butoxycarbonyl)-6-methyl-3,4-dihydro-2(1H)-pyridones have been prepared by means of a modified Hantzsch reaction using commercially available starting materials. An easy removal of the tert-butyl group of these pyridones and subsequent reaction with cesium carbonate and chloromethyl 2-methylpropanoate provided us suitable substrates (±)-5 to be used in lipase-catalyzed hydrolysis reactions. Lipase B from Candida antarctica (CAL-B) was the most adequate lipase in the hydrolysis of (±)-5. Despite the low enantioselectivity values obtained (E≤12), several optically active pyridone derivatives were finally isolated with high enantiomeric excesses (ee≥91%) and moderate yields.     

Leontopodic acid—a novel highly substituted glucaric acid derivative from Edelweiss (Leontopodium alpinum Cass.) and its antioxidative and DNA protecting properties

Leontopodic acid—a novel full substituted hexaric acid derivative, was isolated from the aerial parts of Edelweiss (Leontopodium alpinum Cass.) as one of the major compounds. The complex structure of leontopodic acid-2-[(3S)-3-hydroxybutanoate]-3,4,5-tris-[(2E)-3-(3,4-dihydroxyphenyl)-2-propenoate]-d-glucaric acid—was elucidated by mass spectrometry, 1D- and 2D NMR spectroscopy and HPLC monitored transesterification. Leontopodic acid exhibited pronounced antioxidative effects in the Briggs-Rauscher (BR) model [(r.a.c.)_m 3.4±0.5] and the trolox equivalent antioxidant capacity (TEAC) method (TEAC value of 1.53±0.11). The antioxidative properties of this compound were confirmed by the 3D method, an in vitro assay evaluating DNA protection against oxidative damage (IC₅₀: 1.89 μM).     

A Morita-Baylis-Hillman adduct allows the diastereoselective synthesis of styryl lactones

We disclosed herein a diastereoselective approach for the total syntheses of (±)-Leiocarpin A and (±)-Goniodiol. These biologically active styryl lactones were obtained from a common intermediate, prepared in five steps and 40% overall yield, using a simple synthetic sequence starting from a Morita-Baylis-Hillman adduct. The total syntheses of these styryl lactones were accomplished in nine steps. This is the first report on the total synthesis of this class of natural products starting from Morita-Baylis-Hillman adduct.