Solid phase synthesis of structurally diverse tetra substituted pyrimidines for potential use in combinatorial chemistry

A new pyrimidine based scaffold has been identified for generation of combinatorial libraries using solid phase technique. The utility of the scaffolds was demonstrated by synthesizing small libraries of 12 substituted pyrimidines (4a-4l).     

Efficient synthesis of taurine and structurally diverse substituted taurines from aziridines

Taurine and substituted taurines were synthesized efficiently from aziridines via ring-opening reaction with thioacetic acid, oxidation with performic acid, and hydrolysis in hydrochloric acid. The current method shows more benefit in purification and efficiency in the preparation of taurine and structurally diverse 2-substituted, 2,2-disubstituted, and 1,2-, 2,2-, and 2,N-alkylene taurines.     

Design and synthesis of novel 5,6-bisindolylpyrimidin-4-ones structurally related to ruboxistaurin (LY333531)

2,3-Bis(1-methyl-1H-indol-3-yl) methyl-3-oxopropionate is a key intermediate in the synthesis of a new family of LY333531 analogues. Base-mediated cyclocondensation with thiourea afforded novel 5,6-bis(1-methyl-1H-indol-3-yl)-2-thioxo-2,3-dihydropyrimidin-4(1H)-one, which was efficiently converted to the pyrimidin-2,4(1H,3H)-dione congener. Synthesis of a six-membered K-252c analogue, 5,6-bis(1-methyl-1H-indol-3-yl)pyrimidin-4(3H)-one, is also described.     

Synthesis of certain substituted pyrimidines as potential schistosomicidal agents

A convenient route is reported for the synthesis of seven new pyrimidine derivatives namely: 2-bromometh-yl-4,6-dimethoxypyrimidine ( 3 ), 2-dibromomethyl-4,6-dimethoxypyrimidine ( 4 ), 2-acetoxymethyl-4,6-dimeth-oxypyrimidine ( 5 ), 2-hydroxymethyl-4,6-dimethoxypyrimidine ( 6 ), 4,6-dimethoxypyrimidine-2-carboxaldehyde ( 7 ), 2-acetoxymethyl-6-methoxy-3,4-dihydropyrimidin-4-one ( 8 ) and 2-hydroxymethyl-3,4-dihydro-6-methoxy-pyrimidin-4-one ( 9 ).     

Design and synthesis of a structurally constrained aminoglycoside

The synthesis of a constrained tricyclic aminoglycoside derivative is described. This constrained compound fixes the spatial orientation of two critical rings for the minimal motif for binding to biological macromolecules such as RNA and proteins. Methanolysis of neomycin B under acidic conditions produced the bicyclic neamine. Transient protection by the Cu2+ ion and regioselective introduction of protective groups led to intermediate 7, which was used for a key annulation reaction that introduced the tricyclic nucleus into the structural framework. A final hydrogenolysis step to remove the protective groups produced the desired target molecule. The efficient eight-step synthesis was accomplished in 8% overall yield.     

去甲斑蝥素抗惊厥衍生物的设计与合成

癫痫是一种由多种原因引起的脑部神经元群阵发性异常放电所致的植物神经功能异常的疾病,以反复发作性、短暂性、通常为刻板性的中枢神经系统功能失常为特征的综合征.世界上大约4千万到5千万人遭受癫痫的折磨,其中80%在发展中国家[1].     

Design,synthesis, and anti- Trypanosoma cruzi evaluation of a new class of cell-growth inhibitors structurally related to Fenoxycarb

Several compounds, structurally related to the insect-growth regulator Fenoxycarb ( 1 ), were designed and synthesized. These compounds were tested as growth inhibitors of Trypanosoma cruzi cells (epimastigotes). Compounds 6, 16, 18 , and 22 were very active against T. cruzi making them promising good candidates either for blood-bank sterilization of Chagas'-disease surveillance, while compounds 11 , 12 , 13 , and 19 showed a moderate degree of activity.     

Synthesis of certain 1,7,7-trimethyl-bicyclo[2.2.1]heptane derivatives with anticonvulsant, hypoglycemic and anti-inflammatory potential

Starting from (1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylideneamino)-acetic acid methyl esters 6a, 6b, the aryl esters of exo-2-[methyl-(1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amino]-ethanol (10a-f) and exo-2-[methyl-(1,7,7-trimethyl-bicyclo[2.2.1]hept-2-yl)-amino-2-phenyl-ethanol (10g-n) are prepared. Also, from the reaction of 1,7,7-trimethyl-bicyclo[2.2.1]heptan nitramine 4 with either 2-amino-1-(4-nitrophenyl)-propane-1,3-diol (17) or 1-aminomethyl-cyclohexanol (18), the alcohol exo-1-[(1,7,7-trimethyl-bicylo[2.2.1]hept-2-ylamino)-methyl]-cyclohexanol (13), exo-1-(4-aminophenyl)-2-(1,7,7-trimethyl-bicyclo[2.2.1]hept-2-ylamino)-propane-1,3-diol (14) and 1-(4-aminophenyl)-2-[methyl-1,7,7-trimethylbicyclo[2.2.1]hept-2-yl]-amino]-propane-1,3-diol (16) are synthesized. At a dose level of 12.5 mg/kg, compounds 16 and 14 show a significant anticonvulsant protection against pentylenetetrazole seizures (100% and 83% protection, respectively) compared with diphenylhydantoin sodium (50 mg/kg, 100%) and deramciclane fumarate (25 mg/kg, 83%), used as reference drugs. Compound 10b at dose level of 50 mg/kg displayed 41%, hypoglycemic activity, compared with gliclazide (10 mg/kg, 23%) as reference drug. Furthermore, the prepared compounds are screened for their anti-inflammatory potential at a dose level of 50 mg/kg. Compounds 10i, 10g, 14 and 10m exhibited 92%, 90%, 88% and 80% inhibition in rat paw weight, respectively, with no sign of ulcerogenicity, compared with indomethecin (5 mg/kg, 81%).     

Design and synthesis of semiflexible substituted polyacetylenes with helical conformation

In this review article, we summarize our recent efforts on the design and synthesis of helical polymers from propiolic esters. Stereoregular cis-transoidal poly(propiolic esters) prepared with Rh catalysts have proven to possess semiflexible main chain, which drives the main chain to the helical conformation with long persistence length. Based on the chiroptical properties of poly(propiolic esters) bearing various chiral pendants, we established the design strategy for the production of well-ordered helical poly(propiolic esters). NMR study of various poly(propiolic esters) enabled estimation of not only the activation energy of helix reversal, but also the free energy difference between the helical and disordered states. The helix sense of poly(propiolic esters) is determined by the configuration of the chiral center, structure of the pendant groups, temperature, and solvent.     

Synthesis of aminopyrimidylindoles structurally related to meridianins

The synthesis of new meridianin derivatives substituted at the C-5′ position of the 2-aminopyrimidine ring by various aryl groups and substituted or not by a methyl group on the indole nitrogen is described. The 2-aminopyrimidine ring was obtained via a Bredereck synthesis. Aryl groups were introduced by Suzuki cross-coupling after bromination of the 2-aminopyrimidine ring at the C-5′ position.     

Inositolphosphoglycan mediators structurally related to glycosyl phosphatidylinositol anchors: synthesis, structure and biological activity

The preparation of the pseudopentasaccharide 1a, an inositol-phosphoglycan (IPG) that contains the conserved linear structure of glycosyl phosphatidylinositol anchors (GPI anchors), was carried out by using a highly convergent 2+3-block synthesis approach which involves imidate and sulfoxide glycosylation reactions. The preferred solution conformation of this structure was determined by using NMR spectroscopy and molecular dynamics simulations prior to carrying out quantitative structure--activity relationship studies in connection with the insulin signalling process. The ability of 1a to stimulate lipogenesis in rat adipocytes as well as to inhibit cAMP dependent protein kinase and to activate pyruvate dehydrogenase phosphatase was investigated. Compound 1a did not show any significant activity, which may be taken as a strong indication that the GPI anchors are not the precursors of the IPG mediators.     

Syntheses of some indazoles structurally related to equilenin

This study reports the complete synthesis and characterization of the 15, 16-diazaequilenin derivative 10,11-dihydro-3H-naphth[1,2-g]indazol-7-ol ( 2b ) as well as the methyl ether 2a of the above compound and the novel “model” compound 4,5-dihydro-1H-benz[g]indazol-7-ol ( 3b ). Indazoles 2a and 3a have demonstrated in vitro activity against a variety of microorganisms.     

Synthesis of certain 1-β-D-ribofuranosyl-1,2-dihydro-2-oxopyridines structurally related to nicotinamide ribonucleoside

Several substituted 1-β-D-ribofuranosyl-1,2-dihydro-2-oxopyridines have been prepared as congeners of nicotinamide ribonucleoside. Direct glycosylation of the silylated 3-ethylcarboxylate 5 or 3-carbamoyl 6 derivative of 1,2-dihydro-2-oxopyridine with 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose ( 7 ) in the presence of trimethylsilyl triflate gave the corresponding blocked nucleosides 8 and 9 , respectively in good yield. Ammonolysis of 8 and 9 with methanolic ammonia furnished 1-β-D-ribofuranosyl-1,2-dihydro-2-oxopyridine-3-carboxa-mide ( 10 ), the structure of which was established by single-crystal X-ray diffraction analysis. Thiation of 9 with Lawesson's reagent and subsequent deacetylation of the thiated product 11 with methanolic ammonia furnished 1-β-D-ribofuranosyl-1,2-dihydro-2-oxopyridine-3-thiocarboxamide ( 12 ). Modification of the carbo-nitrile function of 1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1,2-dihydro-2-oxopyridine-4-carbonitrile ( 13 ) gave a series of 4-substituted-1-β-D-ribofuranosyl-1,2-dihydro-2-oxopyridines, in which the 4-substituent is a thiocarboxamide 15 , carboxamide 16 , carboxamidoxime 17 , carboxamidine 18 and aminomethyl 19 group. None of these compounds exhibited any significant antitumor or antiviral effects in vitro.     

Synthesis of certain substituted triphenylcarbinols

Conclusion Methods were developed for synthesizing triphenylcarbinol derivatives, possessing acetyl groups or fragments with a triple bond as substituents.Translated from Izvestiya Akademii NaukSSSR, SeriyaKhimicheskaya, No. 1, pp. 208–210, January, 1967.     

The synthesis and chemical reactivity of 6-selenoguanosine and certain related derivatives

The synthesis of 6-selenoguanosine ( 2 ) has been accomplished by a nucleophilic displacement of the chloro group from 2-amino-6-chloro-9-(β- D -ribofuranosyl)purine ( 1 ) with either selenourea or sodium hydrogen selenide. Treatment of 2 with Raney nickel has revealed that the seleno group can be removed much easier under these conditions than the corresponding mercapto group. Alkylation of 2 with several alkylating agents occurred at the exocyclic 6-seleno group to furnish several 6-alkylseleno-2-amino-9-(β- D -ribofuranosyl)purines. Nucleophilic displacement of the 6-benzylseleno group from 2-amino-6-benzylseleno-9-(β- D -ribofuranosyl)purine ( 3c ) with sodium methoxide has been observed to occur at a faster rate than that observed for the corresponding 6-benzylmercapto derivative. A study on the relative stability between 2 and 6-seleno-9-(β- D -ribofuranosyl)purine toward basic conditions has revealed that the amino group at position two imparts an increase in stability.     

Synthesis of new ether glycerophospholipids structurally related to modulator

A series of new glycerophospholipids, bearing a short-chain carboxylic acid in position sn-1 and phosphocholine or phosphoserine in postion sn-3 of glycerol, have been prepared in good overall yields. Compound 11, 1-0-(6-carboxyhexyl)-sn-glycero-3-phosphoserine, a strict analog of the structure proposed for modulator, has been synthesized in a stereoselective way from (R)-1,2-isopropylideneglycerol 1.     

Enzymatic enantiomeric resolution of phenylethylamines structurally related to amphetamine

Both enantiomers of several phenylethylamines, structurally related to amphetamine, have been prepared in good yields and excellent enantiomeric purity by enzymatic kinetic resolution using CAL-B and ethyl methoxyacetate as the acyl donor. In the case of the 4-hydroxyderivative of amphetamine (compound 4i), the S enantiomer racemized possibly in a dynamic kinetic resolution (DKR) under the enzymatic conditions used.