30273-65-5

Upstream product

• 867-13-0 diethoxyphosphoryl-acetic acid ethyl ester 
• 86-81-7 3,4,5-trimethoxy-benzaldehyde 
• 64-17-5 ethanol 
• 141-82-2 malonic acid 
• 141-78-6 ethyl acetate 
• 4521-61-3 3,4,5-Trimethoxybenzoyl chloride 
• 140-88-5 ethyl acrylate 
• 20329-98-0 (E)-3,4,5-trimethoxy-cinnamic acid 
• 541-41-3 chloroformic acid ethyl ester 
• 1099-45-2 ethyl (triphenylphosphoranylidene)acetate 
• 20329-99-1 (Z)3,4,5-trimethoxycinnamic acid 
• 18638-99-8 3,4,5-trimethoxybenzylamine 
• 31930-36-6 ethyl (Z)-3-iodopropenoate 
• 2675-79-8 1-bromo-3,4,5-trimethoxybenzene 

Downstream Products

• 1253204-25-9 C₁₄H₂₀O₇ 
• 63541-21-9 (E)-5-(3-chloroprop-1-en-1-yl)-1,2,3-trimethoxybenzene 
• 88197-48-2 (E)-1-{4-[2-oxo-2-(pyrrolidin-1-yl)ethyl]piperazin-1-yl}-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one 
• 88053-13-8 N-(3,4,5-trimethoxy cinnamoyl)-piperazine 
• 20069-09-4 piperlongumine 

Relevant academic research and scientific papers

First synthesis of tabamides A–C and their derivatives: In vitro nitric oxide inhibitory activity

The first synthesis of natural phenolic amides, tabamides A–C (1–3), and their derivatives (4–12) was accomplished using Stobbe condensation and amide coupling reactions as key steps. The in vitro nitric oxide (NO) inhibitory effects of these compounds in LPS-induced RAW-264.7 macrophages were evaluated as an indicator of anti-inflammatory activity. All compounds tested had a concentration-dependent inhibitory effect on NO production by RAW-264.7 macrophages without significant cytotoxicity. Compound 6, a tabamide A derivative (IC50 = 82.6 μM), followed by tabamide A (1, IC50 = 100.7 μM), was the most potent from the series. The present study revealed that tabamide A (1) could be considered as a lead structure to develop NO production-targeted anti-inflammatory agents.

Hypervalent iodine(iii) induced oxidative olefination of benzylamines using Wittig reagents

We have developed hypervalent iodine(iii) induced oxidative olefination of primary and secondary benzylamines using 2C-Wittig reagents, which provides easy access to α,β-unsaturated esters. Mild reaction conditions, good to excellent yields with high (E) selectivity, and a broad substrate scope are the key features of this reaction. We have successfully carried out the gram-scale synthesis of α,β-unsaturated esters.

Synthesis method of beta-chloro acid ester and alpha, beta-unsaturated acid ester compound

The invention belongs to the technical field of organic chemistry, and particularly relates to a synthesis method of beta-chloro acid ester and an alpha, beta-unsaturated acid ester compound. The structure of the compound is characterized by 1H NMR and 13C NMR and is confirmed. The method comprises the steps of by taking acetonitrile as a solvent, carrying out fragmentation on olefin, chlorooxalic acid monoester and 2, 6-dimethyl pyridine under a photocatalytic condition to generate an alkoxyacyl free radical intermediate, carrying out free radical addition reaction on the alkoxyacyl free radical intermediate and the olefin to generate carbon free radicals, then carrying out chlorination reaction to obtain the beta-chloro acid ester compound, and carrying out dehydrochlorination reaction under a DBU condition to generate the alpha, beta-unsaturated acid ester compound. The preparation method of the compound disclosed by the invention has the advantages of starting from olefin, being mild in condition, simple and efficient, strong in functional group compatibility and wide in substrate application range, and various beta-chloro acid ester and alpha, beta-unsaturated acid ester compounds can be synthesized from highly commercialized raw materials. On the basis of photoreaction of fluid chemistry, a target product can also be obtained with a relatively good yield, and the method has very good industrial and medicinal chemistry application values.

Accessing dihydro-1,2-oxazine via cloke-wilson-type annulation of cyclopropyl carbonyls: application toward the diastereoselective synthesis of pyrrolo[1,2- b][1,2]oxazine

A convenient additive-free synthesis of dihydro-4H-1,2-oxazines via a Cloke-Wilson-type ring expansion of the aryl-substituted cyclopropane carbaldehydes with the hydroxylamine salt is introduced. Comparatively less active cyclopropyl ketones also follow a similar protocol if supplemented by catalytic p-toluene sulfonic acid monohydrate. The transformation is performed in an open-to-air flask as it shows negligible sensitivity toward air/moisture. Dihydro-4H-1,2-oxazines when subjected to cycloaddition with the cyclopropane diester afford a trouble-free formulation of the valued hexahydro-2H-pyrrolo[1,2-b][1,2]oxazine derivatives. A cascade one-pot variant of this two-step strategy offers a comparable overall yield of the final product.

Iron-Catalyzed Cross-Coupling of Bis-(aryl)manganese Nucleophiles with Alkenyl Halides: Optimization and mechanistic investigations

Various substituted bis-(aryl)manganese species were prepared from aryl bromides by one-pot insertion of magnesium turnings in the presence of LiCl and in situ trans-metalation with MnCl2 in THF at ?5 ?C within 2 h. These bis-(aryl)manganese reagents undergo smooth iron-catalyzed cross-couplings using 10 mol% Fe(acac)3 with various functionalized alkenyl iodides and bromides in 1 h at 25 ?C. The aryl-alkenyl cross-coupling reaction mechanism was thoroughly investigated through paramagnetic 1H-NMR, which identified the key role of tris-coordinated ate-iron(II) species in the catalytic process.

Preparation method for cinepazide maleate

The invention provides a preparation method for cinepazide maleate, which comprises the following steps of: (1) carrying out Wittig reaction on 3, 4, 5-trimethoxybenzaldehyde serving as an initial rawmaterial and phosphine ylide to obtain (E)-3, 4, 5-trimethoxyethyl cinnamate (intermediate I), (2) hydrolyzing the (E)-3, 4, 5-trimethoxyethyl cinnamate to obtain a key intermediate 3, 4, 5-trimethoxy cinnamic acid (intermediate II), (3) in the presence of 1-hydroxybenzotriazole, triethylamine and carbodiimide hydrochloride, coupling the intermediate I with anhydrous piperazine to synthesize 1-(3, 4, 5-trimethoxycinnamoyl) piperazine (intermediate III), (4) reacting the 1-(3, 4, 5-trimethoxycinnamoyl) piperazine with 2-bromo-1 (pyrrolidine-1-yl) ethyl ketone to generate cinepazide (an intermediate IV), and (5) salifying the cinepazide in the step (4) and maleic acid to generate the target product cinepazide maleate. The preparation method has the advantages of cheap and easily available raw materials, simple operation, short production period, high yield, easy purification, good control of the product quality, reduction of the pollutant discharge, environmental protection, and realization of industrial production.

Synthesis of Functionalized Indolines and Dihydrobenzofurans by Iron and Copper Catalyzed Aryl C-N and C-O Bond Formation

A simple and effective one-pot, two-step intramolecular aryl C-N and C-O bond forming process for the preparation of a wide range of benzo-fused heterocyclic scaffolds using iron and copper catalysis is described. Activated aryl rings were subjected to a highly regioselective, iron(III) triflimide-catalyzed iodination, followed by a copper(I)-catalyzed intramolecular N-or O-arylation step leading to indolines, dihydrobenzofurans, and six-membered analogues. The general applicability and functional group tolerance of this method were exemplified by the total synthesis of the neolignan natural product, (+)-obtusafuran. DFT calculations using Fukui functions were also performed, providing a molecular orbital rationale for the highly regioselective arene iodination process.

Excavating precursors from the traditional Chinese herb Polygala tenuifolia and Gastrodia elata: Synthesis, anticonvulsant activity evaluation of 3,4,5-trimethoxycinnamic acid (TMCA)ester derivatives

Epilepsy is a group of neurological disorders characterized by recurrent seizures that disturbs about 60 million people worldwide. In this article, a novel series of 3,4,5-trimethoxycinnamic acid (TMCA)ester derivatives 1–35 were designed inspired from the traditional Chinese herb pair drugs Polygala tenuifolia and Gastrodia elata and synthesized followed by in vivo and in silico evaluation of their anticonvulsant potential. All the synthesized derivatives were biologically evaluated for their anticonvulsant potential using two acute model of seizures induced in mice, the maximal electroshock (MES)and sc-pentylenetetrazole (PTZ)models. Simultaneously, the motor impairment as a surrogate of acute neurotoxicity and in vitro screening of cytotoxicity against HepG-2 cells line were assessed through the rotarod performance test and CCK-8 assay, respectively. In addition, the physicochemical and pharmacokinetic parameters of the active compounds were determined. Our results showed that compounds 5, 7, 8, 13, 20, 25, 28, 30 and 32 exhibited preferable anticonvulsant activity in primary evaluation, with compounds 28 and 32 being the most promising anticonvulsant agents in according to results of subsequent pharmacology and toxicity evaluation. Additionally, the molecular modeling experiments predicted good binding interactions of part of the obtained active molecules with the gamma-aminobutyric acid (GABA)transferas. Therefore, it could be concluded that the synthesized derivatives 28 and 32 would represent useful lead compounds for further investigation in the development of anticonvulsant agents.

Mild, Metal-Free and Protection-Free Transamidation of N-Acyl-2-piperidones to Amino Acids, Amino Alcohols and Aliphatic Amines and Esterification of N-Acyl-2-piperidones

Amides are indispensable building blocks of biological systems, pharmaceuticals, and materials. We report a highly selective method for the synthesis of amides via transamidation process. Transamidation of N-acyl-2-piperidones with a broad range of amines is demonstrated under exceedingly mild and metal-free reaction condition that relies on the amide bond twist to weaken the amidic resonance. Transamidation proceeds under the neat condition at room temperature, in short reaction times (30–90 min) with good yields. Considerable variation is tolerated with both amine and imide substrates. Of note, amines bearing carboxylic acids (glycine and serine) and hydroxyl groups (dopamine, tyramine, etc.) are well tolerated which are otherwise problematic under the metal-catalyzed protocol. Our current method is applicable for transamidation of both alkyl and aryl-N-acyl-2-piperidones. The practical value of the method is highlighted by the synthesis of four natural product amide alkaloids in high yields under mild reaction conditions. In the absence of nucleophilic amines, N-acyl-2-piperidones undergoes esterification with EtOH at elevated temperature. Single crystal X-ray analysis of an N-acyl-2-piperidone shows amide bond twist, τ = –20.39° and pyramidalization, χN = –11.73°. This weakens the amidic conjugation and might be the factor controlling the reactivity and selectivity of these imides. We envision that the N-acyl-2-piperidone scaffold would be useful in the synthesis of pharmaceuticals and materials.

Design, Antileishmanial Activity, and QSAR Studies of a Series of Piplartine Analogues

Piplartine is an alkamide found in different Piper species and possesses several biological activities, including antiparasitic properties. Thus, the aim of the present study was to evaluate a series of 32 synthetic piplartine analogues against the Leishmania amazonensis promastigote forms and establish the structure-activity relationship and 3D-QSAR of these compounds. The antileishmanial effect of the compounds was determined using the MTT method. Most compounds were found to be active against L. amazonensis. Among 32 assayed derivatives, compound (E)-(-)-bornyl 3-(3,4,5-trimethoxyphenyl)-acrylate exhibited the most potent antileishmanial activity (IC50 = 0.007 ± 0.008 μM, SI > 10), followed by benzyl 3,4,5-trimethoxybenzoate (IC50 = 0.025 ± 0.009 μM, SI > 3.205) and (E)-furfuryl 3-(3,4,5-trimethoxyphenyl)-acrylate (IC50 = 0.029 ± 0.007 μM, SI > 2.688). It was found that the rigid substituents contribute to increasing antiparasitic activity against L. amazonensis promastigotes. The presence of the unsaturated heterocyclic substituent in the phenylpropanoid chemical structure (furfuryl group) resulted in a bioactive derivative. Molecular simplification of benzyl 3,4,5-trimethoxybenzoate by omitting the spacer group contributed to the bioactivity of this compound. Furthermore, bornyl radical appears to be important for antileishmanial activity, since (E)-(-)-bornyl 3-(3,4,5-trimethoxyphenyl)-acrylate exhibited the most potent antileishmanial activity. These results show that some derivatives studied would be useful as prototype molecules for the planning of new derivatives with profile of antileishmanial drugs.