Thermodynamics of a series of harmine alkaloid derivatives

The enthalpies of solution in water and ethanol of a series of harmine alkaloid derivatives, harminium di(o-carborano-1,2-dimethyl)borate, harminium tosylate, harminium thiocyanate, N(2)-hydroxyharminium hydrogen sulfate, and adduct of harmine N-oxide with phthalic anhydride, were determined by isothermal calorimetry. The standard heats of combustion, melting, and formation of these compounds were calculated by approximate methods.     

A convenient synthesis of 8-substituted indolizines as precursors to 5-substituted cycl{3.2.2}azine derivatives

The synthesis of 8-substituted indolizines is described via a two step process in which a 1,4-diketone, containing a rerf-butyl group, is cyclocondensed with a trialkylsilyl protected pyrrole to provide 5,8-disubstituted indolizines in higher yields than the identical reaction with unprotected pyrrole. Cleavage of the tert-butyl group from the indolizine 5-position, by treatment with 85% phosphoric acid, provides 8-substituted indolizines in good yields. Treatment of 8-substituted indolizines with dimethyl acetylenedicarboxylate, in the presence of palladium-on-carbon, provides novel 5-substituted cycl{3.2.2) derivatives.     

Isolation of a new carboline alkaloid from Trigonostemon lii

A new carboline alkaloid, 1-(7-methoxy-quinolinyl-4′-yl)-3,4-dihydro-β-carboline (1), was isolated from the leaves and twigs of Trigonostemon lii Y.T. Chang, together with three known ones, trigonostemonines C and D (2 and 3), and trigonoliimine A (4). Their structures were elucidated by spectroscopic analyses, including 2D-NMR techniques.     

Synthetic entries to 6-fluoro-7-substituted indole derivatives

Three practical synthetic entries of functionalized 6-fluoro-7-substituted indole derivatives were developed in connection with the preparation of 7-fluoro-8-substituted-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid derivatives 11 . The first route, which permits group modification about position 8 of the pyranoindole skeleton, employs 2-bromo-3-fluoroaniline ( 18 ) as a key intermediate, the preparation of which was achieved by either a novel ortho metalation of 15 or via the intermediacy of 22 . The second route utilizes 32 to append a terminally functionalized three carbon side chain onto the indole template and in addition leads to 43 from 40 . The third route to the 7-fluoro-8-substituted-pyranoindole skeleton complements route two in that the synthetic pathway exploits 32 in a nucleophilic fashion to construct a terminally functionalized two carbon appendage onto the indole nucleus.     

Diastereospecific synthesis of new 4-substituted l-theanine derivatives

Considering the biological activity of l-theanine as a potent agonist of NMDA receptors, impacting on glutamatergic synapse activity, we have developed an asymmetric synthesis of new enantiomerically pure 4-substituted l-theanine derivatives. The key step is a stereospecific alkylation on a previously synthesized and correctly protected (S)-pyroglutamate.     

Convenient synthesis of N1-substituted orotic acid derivatives

A convenient and efficient method for the synthesis of N1-substituted orotic acid derivatives is reported. The synthetic route utilizes substituted maleimide as synthetic intermediate and takes only four simple steps from readily available starting materials. As a result, orotic acid derivatives with various alkyl and aromatic groups at N1 can be readily synthesized.     

A new versatile synthesis of 4-substituted diaminopyridine derivatives

A new convenient method for the synthesis of substituted 2,6-diacetamido pyridines has been developed. It starts from 4-hydroxypyridine and comprises the introduction of the amino groups by the Chichibabin reaction. After several protection and deprotection steps 2,6-diacetamido-4-hydroxy pyridine is obtained, which is regarded as a key compound for the synthesis of various substituted 2,6-diacetamido pyridines. It is shown that the free hydroxy group is susceptible for nucleophilic substitution. This provides an easy access to the introduction of different functional groups at 4-position of 2,6-diacetamido pyridine. The advantages over other procedures described in the literature are discussed.     

Electrochemical approach for synthesis of 3-substituted indole derivatives

An efficient and economical method was developed for synthesis of 3-substituted indole by using electrochemically induced condensation of various aldehyde, indole and malononitrile.     

Chemo-enzymatic synthesis of chiral 2-substituted succinic acid derivatives

Prochiral discrimination by the biocatalyst Alcalase^®, an enzyme preparation of subtilisin Carlsberg, was used to effect enantio- and regioselective monohydrolysis of a variety of (RS)-2-substituted succinate diesters to afford the corresponding half esters in modest to excellent enantiomeric excesses (>99%). Exploitation of malonate chemistry, as well as recycling of the unhydrolyzed isomer from the enantioselective hydrolysis, has resulted in a process which is both practical and economical.     

New synthesis of 3-methoxy-4-substituted pyrazole derivatives

A simple and efficient protocol for the synthesis of 3-methoxy-4-arylmethylene- and 3-methoxy-4-heteroarylmethylenepyrazoles has been developed. These derivatives are obtained in one step from alcohols 3 or 8a-b.     

Synthesis of some 2-substituted pyrrolidine alkaloid analogues: N-benzyl-2-(5-substituted 1,3,4-oxadiazolyl) pyrrolidine derivatives and pharmacological screening

Six of N-benzyl-2-(5-substituted 1,3,4-oxadiazolyl) pyrrolidine derivatives 5(a-f) were synthesized from l-proline and characterized by IR, 1H NMR, 13C NMR, and GC–MS. All compounds were tested for antioxidant activity in vitro by the DPPH method. The decrease in absorption of the reaction mixture is considered to have strong antioxidant activity. Among the composites (2, 3, the 5 (b-f)) which bear N-benzyl-2-(5-substituted 1,3,4-oxadiazolyl) pyrrolidine moieties are the most active because they contain donor groups: -Ph-(p-NH₂); -Ph-(p-F); -Ph-(p-Cl); N-Bz-Pyrrolidyl-. Antibacterial activities of the synthetic compounds assessed using the paper disk diffusion and broth dilution methods against Gram-negative bacteria: Escherichia coli ATCC 25922, Pseudomonas aerugenosa ATCC 27853 and Gram-positive bacteria, Staphylococcus aureus ATCC25923, Enterococcus faecalis (ATCC-29212) derived from ATCC 11778 and they showed a variable effect. Gentamycin was used as a positive reference.     

Studies on 8-methoxyquinolones: synthesis and antibacterial activity of 7-(3-amino-4-substituted)pyrrolidinyl derivatives

A series of 8-methoxyquinolones bearing 3-amino-4-methylpyrrolidines or 3-amino-4-fluoromethylpyrrolidines at the C-7 position was synthesized and their physicochemical and biological properties were evaluated. All of the compounds synthesized showed more potent activity than LVFX (3) against both gram-positive and negative bacteria. Increases in lipophilicity of these compounds had desirable effects on their potency of single intravenous toxicity and pharmacokinetic profiles in animals. Among the compounds synthesized, 1-fluorocyclopropyl derivatives 17 and 20, and 7-(cis-3-amino-4-fluoromethylpyrrolidinyl) derivative 19 (DC-756h) showed negative responses in the micronucleus test in mice while 1-cyclopropyl-7-(3-aminopyrrolidinyl) derivative 16 showed a positive response. These results suggested that the introduction of a fluorine atom into the 3-aminopyrrolidinyl substituent resulted in favorable influence on genetic toxicity as well as into the N-1 cyclopropyl substituent.     

Design synthesis and biological evaluation of 3-substituted triazole derivatives

Based on the active site of lanosterol 14α-demethylase of azole antifungal agents,sixteen 1-(1H-1,2,4-triazole-1-yl)- 2-(2,4- difluorophenyl)-3-(N-n-butyl-N-1-substitutedbenzyl-4-methylene-1H-1,2,3-triazole)-2-propanols have been designed,synthesized and evaluated as antifungal agents.Results of preliminary antifungal tests against eight human pathogenic fungi in vitro showed that some of the compounds exhibited excellent activities with broad spectrum.     

Recent advances in asymmetric synthesis of 2-substituted indoline derivatives

Recent advances in asymmetric synthesis of 2-substituted indoline derivatives are discussed.     

2-取代-环戊烯酮及其衍生物的简易合成

本文报道以2-氯环戊酮的加成重排反应合成2-取代环戊酮。如再引入硫硫双键,则可合成2-取代环戊烯酮。取代环戊酮和取代环戊烯酮是合成药物和合成香料的重要中间体。     

Ammonium metavanadate： A novel catalyst for synthesis of 2-substituted benzimidazole derivatives

Ammonium metavanadate (10 tool%) was found to be a useful catalyst for the synthesis of various 2-substituted aryl benzimidazoles. It was used as an oxidizing agent for the condensation of o-pbenylenediamine with different substituted aryl aldehydes at room temperature in ethanol. The method was proved to be simple, convenient and the product was isolated with good yields (79-91%).     

A facile and rapid one-step synthesis of 8-substituted xanthine derivatives via tandem ring closure at room temperature

N-Bromo succinimide (NBS) was found to be an efficient and regioselective reagent in combination with AIBN for an unprecedented, facile and rapid one-step synthesis of 8-substituted xanthine derivatives at room temperature. The inexpensive, nontoxic and readily available NBS efficiently promoted the condensation of several aryl/cycloaryl/heteroaryl aldehydes with 5,6-diamino-1,3-dimethyluracils in presence of catalytic amount of AIBN in a single step via radical chain reaction. The notable advantages of this protocol were short reaction time, milder reaction conditions, simple work-up procedure, no requirement for chromatographic separation, use of non-hazardous reagent/solvent and applicable to a variety of substrates.