2-Imidazolines. III (1). 1-Aryl- and 1-acyl-2-amino-(ormethoxy)-4,5-diamino-4,5-dihydroimidazoles. Synthesis and properties

Diimmonium salt (5) reacts with guanidines (6) and o-methylisoureas (7) affording 2-amino-4,5-dimorpholinoimidazolines (9) . 1-Aryl-2-amino-4,5-dimorpholinoimidazolines lose the amino functionality under mild acidic conditions with formation of 2-amino-5-morpholinoimidazole derivatives (10) whereas 1-acyl derivatives undergo under the same conditions a ring expansion process leading to pyrimidine derivatives (13) .     

Lactose does not interfere with the analysis of sialic acids as their 1,2-diamino-4,5-methylenedioxybenzene derivatives

In 2007, Martin et al. developed a method for the analysis of sialic acids by HPLC following 1,2-diamino-4,5-methylenedioxybenzene (DMB) derivatisation (Martín et al., Anal Bioanal Chem 387:2943–2949, 2007). Within the article, the authors noted that lactose interfered with the analysis, giving erroneously high results when lactose-containing products were analysed. Such an observation is important when analysing milk-based products, yet was contradictory to the observations of Nakamura et al. (Chem Pharm Bull 35(2):687–692, 1987) who demonstrated that DMB was specific for α-keto acids and did not react with simple sugars such as glucose or lactose. In order to clarify the situation, this phenomenon was investigated and it was confirmed that lactose does not interfere with the analysis. However, it was found that most commercial preparations of lactose do contain small amounts of sialic acids, either as the free monosaccharide or bound to lactose in the form of 3′- and 6′-sialyllactose.     

A new route for the synthesis of 4,5-diamino-6-arylsulfanylpyrimidine derivatives and also purines on their basis

5-Acylamino-4-amino-6-arylsulfanylpyrimidines were formed by the reaction 3-arylsulfanyl-2-acylami- no-3-chloroacrylonitriles with benzamidine. The products were converted into new derivatives of 6-aryl- sulfanyl-substituted purine bases by treatment with polyphosphoric acid.     

Copper-catalyzed synthesis of 2-imidazolines and their N-hydroxyethyl derivatives under various conditions

A rapid and efficient method for the synthesis of 2-imidazolines and their N-hydroxyethyl derivatives from the reaction of aromatic nitriles with ethylenediamine (EDA) or N-(2-aminoethyl)ethanolamine (AEEA) using cupric indole-3-acetate (Cu(II)-(IAA)₂) as a reusable catalyst under reflux and microwave conditions is reported. And seven new N-hydroxyethyl-imidazolines were reported for the first time.     

Short synthesis of enantiopure C2-symmetric 1,2:4,5-diepoxypentane and "pseudo"-C2-symmetric 3-azido-1,2:4,5-diepoxypentane from arabitol

On the basis of our previously described selective protection of arabitol as its 1,2:4,5-bis-pentylidene acetal 5, we report a straightforward synthesis of the novel "pseudo"-C(2)-symmetric 3-azido-1,2:4,5-diepoxypentane building block 4 in 6 steps from arabitol. Using a similar synthetic route, an improved synthesis of the C(2)-symmetrical 1,2:4,5-bis-epoxypentane building block 1 is described, also in 6 steps from arabitol. Both enantiomers of 1 and 4 are accessible, and all reactions involved are easily amenable for large-scale synthesis.     

The synthesis of 3,6-diamino-2,3,4,6-tetradeoxy-dl-threo-hexopyranose derivatives,substrates for the synthesis of negamycin

Three synthetic routes to derivatives of 3,6 - diamino - 2,3,4,6 - tetradeoxy - DL - threo - hexopyranose were investigated. Addition of sodium azide in acetic acid to 6 - phthalimido - 5,6 - dihydro - 2 - pyrone gave 4-azido compound (7) of the erythro configuration. From methyl 2,4 - dideoxy - β -dl- erythro - hexopyranoside threo 4 - phthalimido - 6 - phthalimidomethyl - tetrahydro - 2 - pyrone (17) was obtained in three steps in low overall yield. Addition of sodium azide in acetic acid to butyl 6 - oxo - 2 - hydroxy - hex - 4 - enoate followed by methylation, amonolysis of the ester group, and reduction gave methyl 3,6 - diacetamido - 2,3,4,6 - tetradeoxy - α - DL - threo - hexopyranoside (26).     

Stereoselective synthesis of substituted 2,5-diazabicyclo[2.2.1]heptanes by iodine-mediated cyclization of optically pure compounds containing the 4,5-diamino-1,7-octadiene and 1,2-diamino-4-alkene moieties

3,7-endo-Disubstituted 2,5-diazabicyclo[2.2.1]heptanes were obtained by iodo-cyclization of N,N′-di[(S)-1-phenylethyl]-(E,E)-4,5-diamino-1,8-diphenyl-1,7-octadiene and substituted N,N′-di[(S)-1-phenylethyl]-1,2-diamino-4-alkenes. Removal of only one N-substituent of the bridged piperazines was achieved by reduction with ammonium formate and Pd/C. Unexpected cleavage of the skeleton of vinyl-substituted bridged piperazines was observed using hydrogen, leading to substituted 3-aminopyrrolidines.     

Approach to the synthesis of indoline derivatives from diaryliodonium salts

An effective method of constructing the indoline moiety via intramolecular nucleophilic ring closure of a diaryliodonium salt is described. Diacetoxyiodoarene compounds (1a-1e) were converted into intermediate Koser's reagent and coupled with arylstannanes (7-10) to form diaryliodonium salts (11a-14e). Indoline compounds with different N-protecting groups, 15, 16, 17, and 18, were synthesized in higher yields by treating salts (11a-14e) with Cs(2)CO(3) and TEMPO. Regardless of the electronic environment of five para-substituted iodoarenes and the natures of four N-protected arylstannane groups, the conversion proceeded well to afford corresponding indolines in yields of 72-84 and 70-84%, respectively.     

Heterocyclic amines. A convenient synthesis of 3,5-diamino-1,2,4-triazine derivatives

A facile synthesis of 3, 5-diamino-1, 2,4-triazines (I) via condensations in acidic media of acylnitriles with aminoguanidine and subsequent base-catalyzed cyclization of the resulting acylnitrile amidinohydrazones (IV) is described.     

Irreversible enzyme inhibitors. CXI. Candidate active-site-directed irreversible inhibitors of dihydrofolic reductase derived from 4,6-diamino-1,2-dihydro-l-phenyl-s-triazines. V.

Condensation of 5-(p-nitrophenyl)-2-pentanone with phenylbiguanide hydrochloride (V) gave a 2-methyl-2-(p-nitrophenylpropyl)-1,2-dihydro-s-triazine (IX); hydrogenation of the nitro group to amino followed by bromoacetylation afforded the candidate irreversible inhibitor of dihydrofolic reductase, namely, 2-(p-bromoacetamidophenylpropyl)-4,6-diamino-1,2-dihydro-2-methyl-s-triazine hydrochloride (VIII). Similarly, the o, m, and p-isomers of 5-nitrophenoxy-2-pentanone were converted to the corresponding 2-(bromoacetamidophenoxypropyl)-1,2-dihydro-s-triazines (XI). The four candidate irreversible inhibitors were evaluated on the dihydrofolic reductases from pigeon liver, Walker-256 rat tumor, and L-1210/FR8 mouse leukemia. Only VIII was an irreversible inhibitor; VIII slowly inactivated the L-121-/FR8 mouse leukemia enzyme with a half-life of 2–3 hours at 37°, but VIII showed no inactivation of the other two dihydrofolic reductases—a species specific inactivation.     

2-Ethoxy-3,4-dihydroquinoline in the synthesis of 4,5-dihydroimidazo[1,2-a]quinolines

The amination of 2-ethoxy-3,4-dihydroquinoline by phenacylammonium salts has been studied. The products of this reaction are 2-phenacylamino-3,4-dihydroquinoline hydrochlorides and these are converted to 1-aryl-4,5-dihydroimidazo[1,2-a]quinolines by refluxing in aqueous solution with a catalytic amount of HCl.T. G. Shevchenko Teaching Institute, Chernigov 250038. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 946–949, July, 1997.     

Catalyzed Diels-Alder reaction of alkylidene- or arylideneacetoacetates and Danishefsky's dienes with lanthanide salts aimed at selective synthesis of cis-4,5-dimethyl-2-cyclohexenone derivatives.

The first successful example of the catalyzed Diels-Alder reaction of 1-methoxy-3-trimethylsiloxy-1,3-diene (Danishefsky's diene, 2a), giving the corresponding carbocyclic adducts, is described. The reaction of (Z)-ethylideneacetoacetate 1a with 2a is catalyzed with lanthanide salts such as Yb(OTf)(3) at 0 degrees C, affording the corresponding 2-cyclohexenone 3a in good yield with complete integrity of the starting geometry of 1a. The thermal version of the same cycloaddition results in a decrease in the cis arrangement of the 5-methyl and the 4-alkoxycarbonyl groups on 2-cyclohexenone. The catalyzed reaction of (E)-1a unexpectedly affords the cis-arranged 3a. The reaction path for the catalyzed Diels-Alder reaction is postulated on the basis of these results.     

Functionalization of substituted 2(1H)-pyridones. V. The synthesis of 1,2-dihydro-2-oxo-3,5-pyridinedicarboxylic acid derivatives through a novel dianion route

A new pyridone dianion was prepared by halogen-metal exchange from 5-bromo-1,2-dihydro-2-oxo-3-pyrid-inecarboxylic acid, t-butyl ester and two equivalents of n-butyllithium. This 1,5-dianion readily reacted at C₅ with electrophiles. Quenching with carbon dioxide gave the previously unreported 1,2-dihydro-2-oxo-3,5-pyridine dicarboxylic acid, 3-t-butyl ester. The 5-carboxyl groups were selectively converted to the ethyl ester and the ethyl amide through the 5-imidazolide. The 3-t-butyl ester was easily removed from all derivatives with acid hydrolysis.     

Synthesis of 4,5-decamethyleneimidazole, 4,5-decamethyleneoxazole, 4,5-decamethyleneisoxazole, 4,5-decamethyleneimidazolone-2, and 4,5-decamethylenepyrazole from cyclododecanone derivatives

4,5-Decamethyleneimidazole, 4,5-decamethyleneoxazole, and 4,5-decamethyleneimidazolone-2 were synthesized by reactions of 2-bromocyclododecanone and 2-hydroxycyclododecanone with formamide, ammonium formate, and urea, respectively. Condensation of 2-formylcyclododecanone with hydroxylamine and hydrazine hydrate resulted in 4,5-decamethyleneisoxazole, and 4,5-decamethylenepyrazole, respectively.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 891–893, May, 1994.