Diastereoselective imino-aldol condensation of chiral 3-(p-Tolylsulfinyl)-2-furaldimine and ester enolates

(Ss)-3-(p-Tolylsufinyl)-2-furaldimine was synthesized, and condensation of the chiral furaldimine with lithium ester enolates has been examined. The product distribution of the reaction is dependent upon reaction conditions and on the kind of the substituent placed on the esters. Disubstituted ester enolate resulted in the exclusive formation of (4R)-beta-lactam, while unsubstituted, tert-butyl ester enolate preferentially gave (3R)-beta-amino ester. With the monosubstituted ester enolates, the condensation afforded (4R)-beta-lactams and/or (3R)-beta-amino esters as major products. This method has been applied to an efficient route to chiral furyl beta-lactams.     

Rearrangements of 4-(2-Aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid diethyl ester

The treatment of 4-(2-aminophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinecarboxylic acid diethyl ester (III) with refluxing toluene or pyridine afforded 1,2,3,6-tetrahydro-2,4-dimethyl-2,6-methano-1,3-benzodiazocine-5,11-dicarboxylic acid diethyl ester (IV) as the major product. In addition, the following minor products were isolated: 2-methyl-3-quinolinecarboxylic acid ethyl ester (V), 3-(2-aminophenyl)-5-methyl-6-azabicyclo[3,3,1]-hept-1-ene-2,4-dicarboxylic acid diethyl ester (VI), and 5,6-dihydro-2,4-dimethyl-5-oxobenzo[c][2,7]naphthyridine-1-carboxylic acid ethyl ester (VII). In contrast, acidic conditions caused the conversion of III into V in a 95% yield. The formation of the latter appears to involve IV as an intermediate, since IV degraded rapidly in acid to give V in a quantitative yield.     

Reactions of polyfunctional amines with 3-amino-4-(anilinothio-methylidene)-2-cyano-2-pentenedioic acid diethyl ester

3-Amino-4-(anilinothiomethylidene)-2-cyano-2-pentenedioic acid diethyl ester reacts with ethylenedi-amine, 1,3-propylenediamine and 1,4-butylenediamine affording bicyclic cyclocondensation products. The title compound reacts with diethylenetriamine and 2-(2-aminoethylamino)ethanol to give new seven membered ring tricyclic compounds. The mechanism for these reactions is discussed.     

(R)-4-氰基-3-羟基丁酸乙酯的合成

研究了一条新的路线用于他汀类药物的重要中间体(R)-4-氰基-3-羟基丁酸乙酯的合成. 以廉价、易得的L-(－)-苹果酸为起始原料, 经酯化、还原、溴代和氰化四步反应得到目标化合物(R)-4-氰基-3-羟基丁酸乙酯, 合成总收率为56.7%. 所有中间体和最终产物均由ESI-MS, 1H NMR和13C NMR光谱及比旋光度表征并与文献值比较. 该方法原料易得、操作简便、收率良好, 产物容易分离纯化, 是一条适合大规模制备(R)-4-氰基-3-羟基丁酸乙酯的新合成工艺路线.     

Total synthesis of oxidized phospholipids. 3. The (11E)-9-hydroxy-13-oxotridec-11-enoate ester of 2-lysophosphatidylcholine

A total synthesis of (11E)-9-hydroxy-13-oxotridec-11-enoate ester of 2-lysophosphatidylcholine (HOT-PC) was devised to facilitate identification of this oxidized phospholipid. A lactone, 8-(3-oxo-1H,6H-2-oxinyl)octanoic acid (1), believed to be generated through an intermediate (11E)-9-hydroxy-13-oxotridec-11-enoic acid (HOT), is produced upon autoxidation of linoleic acid. A synthesis of lactone 1 methyl ester was accomplished from HOT involving a novel trans-cis isomerization that is driven to completion by cyclization to a hemiacetal. An alternative route to this carbon skeleton was also achieved that provides the lactone 1 itself.     

3-(2-氧代环烷基)丙酸与(R)-2-硫代四氢噻唑-4-羧酸乙酯的反应

３－（２－氧代环烷基）丙酸与（Ｒ）－２－硫代四氢噻唑－４－羧酸乙酯的反应李叶芝,田颜清,黄化民（吉林大学化学,长春,１３００２３）关键词（Ｒ）－２－硫代四氢噻唑－４－羧酸乙酯,Ｎ－３－（２－氧代环烷基）丙酰－２－硫代四氢噻唑－４－羧酸乙酯,环合反应,...     

药物曲美布汀对映体在涂敷三(4-甲基苯甲酸)纤维素酯手性固定 相上的HPLC分 离

涂敷15%(wt)三(4-甲基苯甲酸)纤维素酯于大孔硅胶担体上,制备手性固定相,以此手性固定相作填料,湿法装填液相色谱柱,直接分离(±)-曲美布汀对映体。确定对映体在固定相与洗脱液之间分配的自由能变之差值、焓变之差值和熵变之差值,考察洗脱液正己烷-异丙醇(v/v)中异丙醇含量在色谱分离对映体性能方面的影响。当洗脱液中异丙醇含量增加时,对映体的容量因子逐渐降低,分离因子变化不大,分离度逐渐降低。     

Synthesis of phenyl analog of retinoic acid methyl ester proceeding from 3-(bromomethyl)but-3-enal diethylacetal

Aromatic analog of retinoic acid methyl ester was prepared using a convenient prenylating agent, 3-(bromomethyl)but-3-enal diethylacetal, and Barbier reaction in the key stage of building up the carbon chain of target molecules. A version is offered of the synthesis of methylidene analog of aromatic retinoic acid.     

A simple and practical approach to enantiomerically pure (S)-3-hydroxy-γ-butyrolactone: synthesis of (R)-4-cyano-3-hydroxybutyric acid ethyl ester

The oxidation of α- or β-(1,4) linked disaccharides or oligosaccharides with cumene hydroperoxide in the presence of a base gave (S)-3,4-dihydroxybutyric acid, which was cyclized under acidic conditions to furnish (S)-3-hydroxy-γ-butyrolactone. This was subsequently converted into (R)-cyano-3-hydroxybutyric acid ethyl ester, an intermediate for statin based drugs and other related compounds.     

Studies on penem and carbapenem. I. Syntheses and oral absorption of ester-type prodrugs of sodium (5R,6S)-2-(2-fluoroethylthio)-6-[(1R)-1-hydroxyethyl]penem-3-c arboxylat e

Acyloxyalkyl esters (2a-d), alkyloxycarbonyloxyalkyl esters (2e-g) and (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl ester (2h) of (5R,6S)-2-(2-fluoroethylthio)-6-[(1R)-1-hydroxyethyl]penem-3- carboxylic acid (1) were synthesized. Enhanced oral absorption was observed in mice reflecting increased lipophilicity, compared with the parent 1 itself. Among them, the ester 2h showed a prolonged plasma level and a large area under the blood concentration-time curve (AUC) in rats. These ester-type prodrugs of penem 1 in phosphate buffer (pH 6.86) were much more stable than those of cephalosporins which easily degraded via isomerization to delta 2 cephalosporins.     

用NaBH4还原3-(3,4-二苄氧基苯基)-2-羟基丙烯酸甲酯

用NaBH4还原3-(3,4-二苄氧基苯基)-2-羟基丙烯酸甲酯得到3-(3,4-二苄氧基苯基)-乳酸甲酯和3,4-二苄氧基苯基-1,2-丙二醇(1)。1的结构经1HNMR,13CNMR和MS确定。     

A crystallization-induced asymmetric transformation to prepare (R)-4-chlorophenylalanine methyl ester

A second order asymmetric transformation of racemic 4-chlorophenylalanine methyl ester was achieved via salt formation with (2S,3S)-(−)-tartaric acid in the presence of salicylaldehyde to afford the desired (R)-enantiomer of 4-chlorophenylalanine methyl ester in good yield and high enantiomeric purity.     

Synthesis of 5-Aryl(heteryl)-1-hydroxyethyl-4-(furyl-2-carbonyl)-3-hydroxy-3-pyrroline-2-ones

5-Aryl(heteryl)-1-hydroxyethyl-4-(furyl-2-carbonyl)-3-hydroxy-3-pyrroline-2-ones were synthesized via reactions of methyl ester of furyl-2-carbonylpyruvic acid with a mixture of aromatic or heterocyclic aldehyde and ethanolamine in dioxane. Antibacterial and antifungal activities of the synthesized compounds was studied.     

1,4-二氢-2,6-二甲基-4-(3-硝基苯基)-3,5-吡啶二羧酸二(2-甲氧基乙基)酯的合成

对1，4－二氢吡啶类钙拮抗剂西尼地平进行了结构修饰。以双乙烯酮和乙二醇单甲醚为原料，经酯化、缩合、氨化和Hantzsch环化等反应合成了1，4－二氢－2，6二甲基－4－（3－硝基苯基）－3，5－吡啶二羟酸二（2－甲氧基乙基）酯，总收率71％。目标产物结构经^1H NMR和MS确证。     

Stereospecific preparation of (Z)- and (E)-2,3-difluoro-3-stannylacrylic ester synthons and a new, efficient stereospecific route to (Z)- and (E)-2,3-difluoroacrylic esters

[reaction: see text] The (Z)-2,3-difluoro-3-stannylacrylic ester is readily prepared from (Z)-1,2-difluorovinyltriethylsilane via stereospecific stannyl/silyl exchange with KF/(Bu3Sn)2O or Bu3SnCl in DMF at 70 degrees C. The corresponding (E)-2,3-difluoro-3-stannylacrylate is prepared by stereospecific carbonylation of (E)-1,2-difluorovinyl iodide followed by low temperature/in situ stannylation of the resultant (Z)-2,3-difluoroacrylic ester. With Cu(I) iodide and Pd(PPh3)4 catalysis, the (Z)- and (E)-stannylacrylate esters readily couple with aryl iodides and vinyl bromides, as well as 2-iodothiophene, at room temperature to stereospecifically produce the respective (E)- and (Z)-2,3-difluoro-3-aryl substituted acrylic esters or conjugated dienes in high yields.     

Microwave solid phase synthesis, characterization, and antimicrobial activities of one mononuclear manganese(II) complex with 4-chlorobenzoic acid 4-[3-(4-chlorophenyl)-3-hydroxyacryloyl]-3-hydroxyphenyl ester

One mononuclear complex has been designed and synthesized by a β-dikertone ligand 4-chlorobenzoic acid 4-[3-(4-chlorophenyl)-3-hydroxyacryloyl]-3-hydroxyphenyl ester (L) with MnCl₂ · 4H₂O in microwave radiation assistance. The complex was characterized by X-ray crystallography, confirming that the central manganese(II) atom was coordinated by four oxygens from two L and two oxygens from two water. The complex was assayed for in vitro antibacterial (B. subtilis, S. aureus, S. faecalis, P. aeruginosa, E. coli, and E. cloacae) activities and showed better antimicrobial activity against Gram positive strains than Gram negative strains.     

(R)-3-叔丁基二甲基硅氧丁基苯硫醚的合成方法改进

以4-(二甲氨基)吡啶为催化剂,通过(R)-3-叔丁基二甲基硅氧丁醇与甲磺酰氯之间的改进烷基磺酰化反应得到(R)-3-叔丁基二甲基硅氧丁基甲磺酸酯(2b,收率98%),2b再与苯硫酚钠反应生成(R)-3-叔丁基二甲基硅氧丁基苯硫醚(3,总收率89%)。2和3的结构经1H NMR,IR和MS表征。     

4-(N-乙基-3-甲基苯胺基）丁酸甲酯的合成

以γ-丁内酯为起始原料,经开环氯化和醇解反应合成4-氯丁酸甲酯（2）; 2与N-乙基间甲苯胺经亲核取代反应合成了4-(N-乙基-3-甲基苯胺基）丁酸甲酯,纯度97.5%,总收率75.3%,其结构经¹H NMR确证。     

Solvatochromism of 3-[2-(4-diphenylaminophenyl)benzoxazol-5-yl]alanine methyl ester. A new fluorescence probe

The photophysical properties of 3-[2-(4-diphenylaminophenyl)benzoxazol-5-yl]alanine methyl ester (1b) and its Boc derivative (1a) were studied in a series of solvents. Its UV-Vis absorption spectra are less sensitive to the solvent polarity than the corresponding fluorescence spectra which show pronounced solvatochromic effect leading to large Stokes shifts. Using an efficient solvatochromic method, based on the molecular-microscopic empirical solvent polarity parameter E(T)(N), a large change of the dipole moment on excitation has been found. From an analysis of the solvatochromic behaviour of the UV-Vis absorption and fluorescence spectra in terms of bulk solvent polarity functions, f(epsilon(r),n) and g(n), a large excited-state dipole moment (mu(e) = 11D), almost perpendicular to the smaller ground-state dipole moment, was observed. This demonstrates the formation of an intramolecular charge-transfer excited state. Large changes of the fluorescence quantum yields as well as the fluorescence lifetimes with an increase of a solvent polarity cause that the new non-proteinogenic amino acid, 3-[2-(4-diphenylaminophenyl)benzoxazol-5-yl]-alanine methyl ester, is a new useful fluorescence probe for biophysical studies of peptides and proteins.     

((3-(3-硅胶丙基)硫基)丙基)硫酸酯作为可回收催化剂用于合成4,4'-芳亚甲基-双(1H-吡唑-5-醇)(英文)

Sulfuric acid ([3-(3-silicapropyl)sulfanyl]propyl)ester is employed as a recyclable catalyst for the condensation reaction between aromatic aldehydes and 3-methyl-l-phenyl-5-pyrazolone. This condensation reaction was performed in ethanol under refluxing conditions giving 4,4'-alkylmethylene-bis(3-methyl-5-pyrazolones) in 74-90% yields. The heterogeneous catalyst was recycled and used in eleven runs for the reaction between benzaldehyde and 3-methyl-l-phenyl-5-pyrazolone without losing catalytic activity.