乙醛和不饱和三氟甲基酮不对称Aldol反应合成光学活性的β-三氟甲基-β-羟基-δ-戊内酯

以手性伯胺为催化剂催化共轭不饱和三氟甲基酮与乙醛的不对称反应为关键步骤,合成了光学活性的β-三氟甲基?-β-羟基-δ-戊内酯.合成过程中包含乙醛和共轭不饱和三氟甲基酮的不对称Aldol反应、氧化反应、碘内酯化以及脱碘反应.     

高效液相色谱-质谱法鉴定总合草苔虫中的草苔虫内酯成分

 采用高效液相色谱分离与质谱检测的联用技术,对总合草苔虫中的草苔虫内酯成分进行定性分析。在以体积比为80∶20的甲醇-水溶液为流动相、采用ODS柱进行分离的色谱条件下,10种草苔虫内酯成分均可获得良好的分离。分析结果表明：深圳大亚湾产地的总合草苔虫中共含有9种已知和1种未知的草苔虫内酯成分。已知成分分别是bryostatin 4,5,6(9),7,8,10,16,17,18,其中bryostatin 7和17是首次从中国海域总合草苔虫中发现的2种痕量草苔虫内酯。该方法简便、准确、灵敏度高,可以很好的对总合草     

3,7-二甲基-7-羟基-2-辛烯-6-内酯类似物的合成及杀菌活性（英文）

以环氧化-内酯化和Sharpless不对称双羟基化反应作为关键步骤,以55%～90%的总收率实现了消旋及光活性3,7-二甲基-7-羟基-2-辛烯-6-内酯类似物的合成.它们的结构经过~1H NMR, ~(13)C NMR, HR-ESI-MS和X射线衍射的表征.对它们的杀菌活性进行了评价,结果表明活性最好的化合物3-苯基-7-甲基-7-羟基-2-辛烯-6-内酯(4)和3-(呋喃-2-基)-7-甲基-7-羟基-2-辛烯-6-内酯(5)对6种植物病原菌的EC_(50)值为0.5～20.0μg/mL,可以作为先导结构进行进一步结构优化.     

含有二氟亚甲基的Fostriecin类似物的设计和合成研究

Fostriecin是近年来备受瞩目的新型抗肿瘤天然产物.根据构效关系分析,设计了具有潜在更高活性的含有二氟亚甲基的Fostriecin类似物4,并进行了合成研究.目标分子的骨架结构由片段a,b,c经螯合控制的加成反应和Stille偶联反应汇聚合成.在含氟片段a的合成中应用了以下关键反应:(Z)-烯基碘8与溴二氟乙酸乙酯在铜粉作用下的偶联反应;酶动力学拆分构建C-5位的手性中心.合成甲基酮片段b的关键步骤包括:酶动力学拆分构建C-11位的手性中心和CBS不对称还原α,β-不饱和酮23.从商业可得的原料出发,经最长线性步骤18步以1.28%的总产率成功地得到未脱保护的含有二氟亚甲基的Fostriecin类似物42.但在对42脱除保护基时,没有得到目标分子4.这可能是由于偕二氟亚甲基的强吸电子作用使内酯环极化程度增大,从而导致内酯环易发生水解开环反应.     

反相高效液相色谱法同时测定墨旱莲中的蟛蜞菊内酯和异去甲基蟛蜞菊内酯

建立了同时测定墨旱莲中香豆草醚类成分蟛蜞菊内酯和异去甲基蟛蜞菊内酯含量的高效液相色谱法。采用Kromasil C18柱(250 mm×4.6 mm, 5 μm),流动相为甲醇-0.5%醋酸水溶液(体积比为55∶45),流速为1.0 mL/min,检测波长为351 nm,柱温为30 ℃,进样量为20 μL。在上述条件下测得的异去甲基蟛蜞菊内酯和蟛蜞菊内酯的质量浓度分别在1.6~32.0 mg/L和5.6~112.0 mg/L时与色谱峰面积之间的线性关系良好,二者高、中、低浓度条件下的平均加标回收率分别为97.5%～ 98.2%和99.0%～ 100.2%。该方法简便、快速、准确,可作为墨旱莲质量控制的一个有效方法。     

L-抗坏血酸作为手性元用一手性稠环类化合物合成的研究

研究了L－抗坏血酸和甲基乙烯酮不对称反应的控制条件以及后处理方法，经 重结晶得到了产率高（71％）、光学纯度高（≥98% ee）的二环内酯类衍生物3。 通过化学／物理方法、X射线晶体测定了化合物3的物理常数、化学结构、立体化学 以及晶体结构。在此基础上，化合3分别在氯化氢／无水醇介质中(CH_3OH, C_2H_5OH)进一步反应，通过分子内差向异构化／羟醛缩合／亲核脱水反应分别得 到了新的含有多个官能团和多个手性中心的稠环类化合物4a和4b。此研究结果可以 为L－抗坏血酸手性元在不对称合成中应用，为具有生物活性的复杂化合物的合成 提供新的途径。     

L-抗坏血酸作为手性元用一手性稠环类化合物合成的研究

研究了L－抗坏血酸和甲基乙烯酮不对称反应的控制条件以及后处理方法，经 重结晶得到了产率高（71％）、光学纯度高（≥98% ee）的二环内酯类衍生物3。 通过化学／物理方法、X射线晶体测定了化合物3的物理常数、化学结构、立体化学 以及晶体结构。在此基础上，化合3分别在氯化氢／无水醇介质中(CH_3OH, C_2H_5OH)进一步反应，通过分子内差向异构化／羟醛缩合／亲核脱水反应分别得 到了新的含有多个官能团和多个手性中心的稠环类化合物4a和4b。此研究结果可以 为L－抗坏血酸手性元在不对称合成中应用，为具有生物活性的复杂化合物的合成 提供新的途径。     

选择性碘内酯化反应的研究进展

碘内酯化反应是通过含碘试剂与烯酸化合物进行反应生成碘代内酯，该反应具 有较强的区域和立体选择性，在不对称有机合成中起重要作用，主要综述近年来碘 内酯化反应的区域选择性控制和立体选择性控制（包括非对映选择性和对映选择性 控制）及其在不对称合成应用中的进展。     

不对称高效构筑新颖螺环氧化吲哚α-甲基仲康酸酯

关于含三个手性中心的螺环氧化吲哚γ-内酯的不对称合成鲜有报道.丙醛和氧化吲哚烯烃首先经有机催化进行不对称Michael加成反应;随后,在水/油两相条件下,Michael加成物经H_2O_2/K_2CO_3体系调节,进行α-羟基化/半缩醛化的串联反应;最后经氯铬酸吡啶(PCC)氧化,得到新颖的螺环氧化吲哚α-甲基仲康酸酯化合物.该合成策略具有条件温和、收率高(91%~98%)、对映选择性优秀(87%~95%)的特点,为手性多取代的螺环氧化吲哚γ-内酯的合成提供了一种简易的新方法.所有新产物均通过核磁共振谱和高分辨质谱对其结构进行确证.     

催化不对称碘代内酯化反应

卤代内酯化反应是一种重要的化学转变,在有机合成领域被广泛地应用于从不饱和羧酸、羧酸酯或酰胺出发构建具特殊结构的内脂[1].在立体选择性的卤代内酯化反应的研究中,针对由手性底物控制的不对称卤代内酯化反应报导颇多,而通过手性试剂诱导的不对称卤代内酯化反应方面的研究非常有限[2].发展高效手性诱导试剂或催化剂,并将其应用于卤代内酯化反应中,得到具有光学活性的卤代内酯,是近期该研究领域中的核心内容.     

Design,synthesis, and characterization of novel pyrimidines bearing indole as antimicrobial agents

Pyrimidines and pyrimidine bearing indole derivatives are very important species in organic chemistry due to their wide use as bioactive compounds with a broad range of good biological activities. Due to the wide spread of different species of bacteria and fungi nowadays, in the present work, a novel series of indolyl‐pyrimidines (2–13) were synthesized starting from 3‐chloro‐1H‐indole‐2‐carbaldehyde (1) . Elemental analysis, IR, 1H‐NMR, 13C‐NMR, and mass spectral data elucidated the structure of newly synthesized compounds. All compounds were screened for their in vitro antibacterial and antifungal activity, and they demonstrated promising results; all the new compounds synthesized from compound (1) , which allowed reactions with thiourea and ethyl cyanoacetate, gave the target compound (2) , which was used as a precursor for the synthesis of indolylthiazolopyrimidine derivatives (3–8) by reactions with halocarbonyl compounds such as chloroacetone, phancyl bromide, and chloroacetic acid through alkylation of the mercapto group followed by cyclization through a nucleophilic attack. When compound (2) subjected to react with hydrazine hydrate gave 4‐indolyl‐2‐hydrazinopyrimidine (5) , the latter compound, when allowed to react with ethyl chloroacetate or diethyloxalate, gave indolylpyrimidotriazine derivatives (10 , 11) ; in contrast, when the compound reacted with acetic anhydride or formic acid, it gave triazolopyrimidine derivatives (12, 13) .     

First Synthesis of Double Headed 1,2,4‐Triazino[5,6‐b]indole Acyclo C‐Nucleosides

Heterocyclization of bis(2‐oxo‐indol‐3‐ylidene)‐galactaric acid hydrazide ( 3 ) with a variety of one‐nitrogen cyclizing agents gave the corresponding 1,4‐bis{1,2,4‐triazino[5,6‐b]indol‐3‐yl}‐galacto‐tetritols 4–8 . Acetylation of the latter double headed acyclo C‐nucleosides with acetic anhydride in the presence of pyridine at ambient temperature resulted in N‐ and O‐acetylation to give the corresponding 1,2,3,4‐tetra‐O‐acetyl‐1,4‐bis{1,2,4‐triazino[5,6‐b]indol‐3‐yl}‐galacto‐tetritols 9–13 which were found to exist in centro‐symmetric zigzag conformations 20 . The assigned structures were corroborated by ¹H, ¹³C NMR as well as mass spectra.     

Highly Enantioselective Methanolysis of Meso‐Cyclic Anhydride Mediated by Bifunctional Thiourea Cinchona Alkaloid Derivatives: Access to Asymmetric Total Synthesis of (+)‐Biotin

An enantioselective asymmetric total synthesis of (+)?biotin ( 1 ) via the Hoffmann–Roche lactone–thiolactone strategy has been accomplished from commercially available cis‐1,3‐dibenzyl‐2‐imidazolidone‐4,5‐dicarboxylic acid ( 2 ). Strategic transformations include a cinchona alkaloid‐based bifunctional thiourea mediated methanolytic desymmetrization of prochiral cyclic anhydride 3 to produce the enantiomerically enriched precursor of Roche lactone 5 and an improved introduction of the 4‐carboxybutyl side chain at C‐4 position of Roche thiolactone 6 via Grignard reaction.     

Synthesis and properties of organosoluble poly(amide imide imide)s based on tetraimide dicarboxylic acid condensed from 4,4′‐(hexafluoroisopropylidene)diphthalic anhydride, 4,4′‐oxydianiline,and trimellitic anhydride and various aromatic diamines

A novel tetraimide dicarboxylic acid was synthesized with the ring‐opening addition of 4,4′‐(hexafluoroisopropylidene)diphthalic anhydride, 4,4′‐oxydianiline, and trimellitic anhydride in a 1/2/2 molar ratio in N‐methyl‐2‐pyrrolidone followed by azeotropic condensation to tetraimide dicarboxylic acid. A series of poly(amide imide imide)s (PAIIs) with inherent viscosities of 0.8–1.1 dL/g were prepared from tetraimide dicarboxylic acid with various aromatic diamines by direct polycondensation. Most of the PAIIs were readily soluble in a variety of amide polar solvents and even in less polar m‐cresol and pyridine. Solvent‐cast films had tensile strengths ranging from 99 to 106 MPa, elongations at break ranging from 8 to 13%, and initial moduli ranging from 2.0 to 2.3 GPa. The glass‐transition temperatures of these PAIIs were recorded at 244–276 °C. They had 10% weight losses at temperatures above 520 °C in air or nitrogen atmospheres. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 1092–1102, 2002     

Synthesis of reactive three‐arm star‐shaped oligoimides with narrow molecular weight distribution

Series of star‐shaped three arms oligoimides (SOI) with terminal amino groups with narrow MWD ((M_w/M_n = 1.1–2) was synthesized by the one‐stage high‐temperature polycondensation in molten benzoic acid at 140 °C. The (B3+AB′) approach with the “slow addition of monomer” method was used for this synthesis, where B3 is 2,4,6‐tris(4‐aminophenoxy)toluene and AB′ is 3‐aminophenoxy phthalic acid. The SOI arm's length was controlled by the AB′/B3 mole ratio of 10:1, 20:1, 40:1, and 100:1. By the reaction of SOI's terminal amino groups with acetic anhydride, corresponding acetamide derivatives were obtained. SOI synthesized are soluble in selected organic solvents. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 2004–2009     

Asymmetric Synthesis of the C（17）——C（28） Subunit of Didemnaketal B

The stereocontrolled synthesis of the C（17）--C（28） fragment 3 of didemnaketal B was accomplished in 21 steps from the natural （R）-（＋）-pulegone and （S）-（--）-citronellal. The key steps involved diastereoselective construction of two chiral carbon centers through the intramolecular chiral induction and uncommon Julia olefination of ketone forming the E-trisubstituted C（22）--C（23） double bound.     

3,4‐Bis(bromomethyl)thieno[2,3‐b]thiophene: Versatile Precursors for Novel Bis(triazolothiadiazines), Bis(quinoxalines), Bis(dihydrooxadiazoles), and Bis(dihydrothiadiazoles)

A synthesis of novel bis(triazolothiadiazines) 11 , 12 , 13 , 14 , bis(quinoxalines) 16 and 17 , bis(thiadiazoles) 24 and 25 , and bis(oxadiazole) 31 , which are linked to the thieno[2,3‐b]thiophene core via phenoxymethyl group, was reported. Thus, reaction of the bis(α‐bromoketones) 6 and 7 with the corresponding 4‐amino‐3‐mercapto‐1,2,4‐triazole derivatives 8 , 9 , 10 in ethanol–DMF mixture in the presence of a few drops of triethylamine as a catalyst under reflux afforded the novel bis(5,6‐dihydro‐s‐triazolo[3,4‐b]thiadiazines) 11 , 12 , 13 , 14 in 60–72% yields. The bis(quinoxalines) 16 and 17 were also synthesized as a sole product in high yields by the reaction of 6 and 7 with o‐phenylenediamine 15 in refluxing acetonitrile in the presence of piperidine as a catalyst. Cyclization of the bis(aldehyde thiosemicarbazones) 20 and 21 with acetic anhydride afforded the corresponding bis(4,5‐dihydro‐1,3,4‐thiadiazolyl) derivatives 24 and 25 in good yield. Bis(5‐phenyl‐2,3‐dihydro‐1,3,4‐oxadiazole) derivative 31 could be obtained in 67% yield by cyclization of the appropriate bis(N‐phenylhydrazone) 29 in refluxing acetic anhydride for 3 h.     

Synthesis and Reactions of Some Heterocyclic Candidates Based on 2‐Amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene Moiety as Anti‐Arrhythmic Agents

In continuation of our previous work, a series of novel thiophene derivatives 4 , 5 , 6 , 8 , 9 , 9a , 9b , 9c , 9d , 9e , 10 , 10a , 10b , 10c , 10d , 10e , 11 , 12 , 13 , 14 , 15 , 16 were synthesized by the reaction of ethyl 2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carboxylate ( 1 ) or 2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carbonitrile ( 2 ) with different organic reagents. Fusion of 1 with ethylcyanoacetate or maleic anhydride afforded the corresponding thienooxazinone derivative 4 and N‐thienylmalimide derivative 5 , respectively. Acylation of 1 with chloroacetylchloride afforded the amide 6 , which was cyclized with ammonium thiocyanate to give the corresponding N‐theinylthiazole derivative 8 . On the other hand, reaction of 1 with substituted aroylisothiocyanate derivatives gave the corresponding thiourea derivatives 9a , 9b , 9c , 9d , 9e , which were cyclized by the action of sodium ethoxide to afford the corresponding N‐substituted thiopyrimidine derivatives 10a , 10b , 10c , 10d , 10e . Condensation of 2 with acid anhydrides in refluxing acetic acid afforded the corresponding imide carbonitrile derivatives 11 , 12 , 13 . Similarly, condensation of 1 with the previous acid anhydride yielded the corresponding imide ethyl ester derivatives 14 , 15 , 16 , respectively. The structures of newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR, MS spectral data, and elemental analysis. The detailed synthesis, spectroscopic data, LD₅₀, and pharmacological activities of the synthesized compounds are reported.     

Organocatalytic Asymmetric Cascade Reactions of 7‐Vinylindoles: Diastereo‐ and Enantioselective Synthesis of C7‐Functionalized Indoles

The first catalytic asymmetric cascade reaction of 7‐vinylindoles has been established by the rational design of such substrates. Cascade reactions with isatin‐derived 3‐indolylmethanols in the presence of a chiral phosphoric acid derivative allow the diastereo‐ and enantioselective synthesis of C7‐functionalized indoles as well as the construction of cyclopenta[b]indole and spirooxindole frameworks (all >95:5 d.r., 94–>99 % ee). This approach not only addresses the great challenge of the catalytic asymmetric synthesis of C7‐functionalized indoles, but also provides an efficient method for constructing biologically important cyclopenta[b]indole and spirooxindole scaffolds with excellent optical purity. Investigation of the reaction pathway and activation mode has suggested that this cascade reaction proceeds through a vinylogous Michael addition/Friedel–Crafts process, in which dual H‐bonding activation of the two reactants plays a crucial role.     

Total Synthesis of the 7,10‐Epimer of the Proposed Structure of Amphidinolide N,Part I: Synthesis of the C1–C13 Subunit

Amphidinolide N, the structure of which has been recently revised, is a 26‐membered macrolide featuring allyl epoxide and tetrahydropyran moieties with 13 chiral centers. Due to its challenging structure and extraordinary potent cytotoxicity, amphidinolide N is a highly attractive target of total synthesis. During our total synthesis studies of the 7,10‐epimer of the proposed structure of amphidinolide N, we have synthesized the C1–C13 subunit enantio‐ and diastereoselectively. Key reactions include an l ‐proline catalyzed enantioselective intramolecular aldol reaction, Evans aldol reaction, Sharpless asymmetric epoxidation and Tamao–Fleming oxidation. To aid late‐stage manipulations, we also developed the 4‐(N‐benzyloxycarbonyl‐N‐methylamino)butyryl group as a novel ester protective group for the C9 alcohol.