Synthesis of some 8-substituted 5-deazaflavins

Treatment of 8-fluoro-3,10-dimethyl-5-deazaflavin (Ia) with ethyl cyanoacetate in ethanol in the presence of potassium carbonate gave the corresponding 8-(1-cyano-1-ethoxycarbonylmethyl)-5-deazaflavin, which was converted into 3,8,10-trimethyl-5-deazaflavin by refluxing in aqueous dimethylformamide. Treatment of Ia with sodium azide in ethanol yielded 8-azido-3,10-dimethyl-5-deazaflavin (V). Compound V was converted into the corresponding 8-amino-, 8-acetamido-, and 8-benzamido-5-deazaflavins by heating in high boiling alcohols, acetic anhydride, and benzoic anhydride, respectively. Fusion of compound V with dimethyl acetylenedicarboxylate yielded 4,5-bis(methoxycarbonyl)-1-(3,10-dimethyl-5-deazaflavin-8-yl)-1,2,3-triazole.     

Synthesis of water soluble 8-substituted 5-deazaflavins

By oxidative cyclization of 5,5′-arylmethylenebis(6-methylaminouracil) derivatives with diethyl azodicarb-oxylate a number of 5-deazaisoalloxazines were synthesized having at the C(8) position a substituent that causes a bathochromic shift varying between 20 and 130 nm, depending on the substituent. To increase the solubility in aqueous media 8-substituted 5-deazaflavins were prepared having a carboxymethyl group at the N(3) position. The carboxymethyl group was introduced prior to the oxidative cyclization.     

The photoreduction of 8-substituted 5-deazaflavins and the 5-deazaflavin catalyzed photoreduction of methyl viologen

Prolonged illumination of 8-X-5-deazaflavins (X = C1, N(CH₃)₂, NH₂, p-NH₂-C₆H₄) in the presence of an electron donor leads to the formation of a 5,5′-dimer and/or a 6,7-dihydro compound. The course and rate of these photoreductions were established and discussed in terms of electronic and steric effects, exerted by the substituent at position 8 and the electron donor. Pseudo first-order kinetics were found to apply to the photoreduction of 8-X-5-deazaflavins (X = Cl, NH₂, p-NH₂-C₆H₄) while the rate of the photoreduction of 8-X-5-deazaflavin (X = N(CH₃)₂) appeared to contain an autocatalytic element. The catalytic effect of 8-X-5-deazaflavins in the photoreduction of methyl viologen by EDTA was investigated. The substituent effect on the rate of the 8-X-5-deazaflavin mediated photoreduction of methyl viologen by EDTA was found to be comparable with that on the photoreduction rate of 8-X-5-deazaflavin in the presence of EDTA with the exception of 8-X-5-deazaflavin (X = N(CH₃)₂), which showed a remarkable relative enhancement of the reactivity towards methyl viologen photoreduction.     

Synthesis of 2-amino-2-deoxo-5-deazaflavins and related compounds

10-Alkyl-2-amino-2-deoxo-5-deazaflavins were prepared by the condensation of 2-amino-6-chloro-5-formylpyrimidin-4(3H)-one with the corresponding N-alkylanilines. 2-Amino-10-p-tolyl-2-deoxo-5-deazaflavin was prepared by the condensation of 2-amino-6-p-toluidinopyrimidin-4(3H)-one with o-chlorobenzaldehyde. Some reactivities of 2-aminopyrimidin-4(3H)-ones are described.     

Synthesis and characterization of 5-substituted 8-hydroxyquinoline derivatives and their metal complexes

5-Aminomethyl-8-hydroxyquinoline (QN) was synthesized as a scaffold to generate dimers, trimers, and tetramer metalloquinolates. Starting from QN, a series of 5-substituted 8-hydroxyquinoline derivatives conjugated with small bioactive molecules were synthesized. Absorption and emission spectra indicate that these QN derivatives chelate well with metal ions, which may serve as a new platform to explore the applications of metalloquinolates for a variety of potential applications.     

Synthesis of C5-substituted imidazolines

5-(Hydroxymethyl)-3-(t-butyloxycarbonyl)imidazoline 2 was prepared in four steps from 2,3-diaminopropionic acid in 72% overall yield. Mitsunobu reaction with a series of phenol derivatives gave the corresponding 5-(aryloxymethyl)-3-(t-butyloxycarbonyl)imidazolines 8a-l. Phthalimide and N-benzyl trifluoroacetamide also reacted.     

Reactivity of 4a,5-epoxy-5-deazaflavins

Reactions of 4a,5-epoxy-5-deazaflavins with aqueous potassium carbonate, Vilsmeier reagent (dimethylformamide-phosphorus oxychloride), acetic anhydride-acetic acid, pyridine and triethanolamine gave the corresponding oxazolonoquinolines, 5-chloro-5-deazaflavins, 4a,5-diacetoxy-5-deazaflavins, 1,5-dihydro-5-deazaflavin-5-ones, and deoxygenated 5-deazaflavins, respectively.     

Synthesis of ω-substituted 5-alkylorotic acids

The lactone of 5 - -hydroxyethylorotic acid, the thiolactone of 5-(-mercaptoethyl)orotic acid, and 5-(-benzamidobutyl)orotic acid were synthesized from substituted 5-carb-ethoxymethylenehydantoins obtained by the condensation of urea with -ethoxalyl derivatives of -butyrolactone, -thiobutyrolactone, and ethyl -benzamidocaproate. The lactam of 5-(-aminoethyl)orotic acid was synthesized by the ammonolysis of the lactone of 5 -(-hydroxyethyl)orotic acid. The acid hydrolysis of 5-(-benzamidobutyl)orotic acid gave 5-(-aminobutyl)orotic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1280–1282, September, 1971.     

13C NMR spectra of 5-substituted 8-mercaptoquinolines

The increments of the substituents were determined from the ¹³C NMR spectra of 5-substituted quinolines. It is shown that the increments correlate with those in benzenes, as well as with the Swain-Lupton constants. The ¹³C chemical shifts of some 5-substituted 8-mercapto-, 8-(methylthio)-, and 8-hydroxyquinolines were investigated. Their values are in satisfactory agreement with the additive contribution. of the increments of the substituents. The deviations from additivity are associated with the steric hindrance to interaction of the substituents with the ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 932–936, July, 1981.     

Synthesis of N-hydroxymethyl derivatives of 5-substituted tetrazoles

Mixtures of isomeric 1- and 2-hydroxymethyl derivatives are formed in the reaction of tetrazole and 5-alkyltetrazoles with formaldehyde in aqueous media, while only one isomer is formed from 5-phenyl- and 5-trifluoromethyltetrazoles. The structures and ratios of the isomers were determined by PMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 415–418, March, 1983.     

Synthesis of some new 5-substituted 1H-tetrazoles

4-Substituted 1-naphthyl selenocyanates and thiocyanates, as well as 2-naphthyl selenocyanate, were synthesized from the corresponding naphthylamines and were converted into 5-naphthyl-1H-tetrazoles by treatment with sodium azide in the presence of triethylamine hydrochloride in toluene. The structure of the newly synthesized compounds was confirmed by IR, ¹H NMR, and mass spectra. Published in Russian in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 1, pp. 153–155. The text was submitted by the authors in English.     

Synthesis of 1-substituted 2, 5-bischloromethylpyrrolidines

A number of 1-substituted 2, 5-bischloromethylpyrrolidines, cyclic analogs of bis--chloroethylamine, have been synthesized. The previously unreported 1-phenyl- and 1-benzyl-2, 5-bis(N-cycloalkylaminomethyl)pyridines and their methiodides have been obtained.     

Synthesis of 6-substituted 1-alkoxy-5-alkyluracils

Synthesis of 6-substituted 1-alkoxy-5-alkyluracils 2a-c have been achieved from readily accessible 2-alkyl-3,3-di(methylthio)acryloyl chlorides 4a,b in high overall yields. Treatment of 4a,b with silver cyanate followed by reaction of the resulting isocyanates 5a,b with an appropriate alkoxyamine afforded N-alkoxy-N′-[2-alkyl-3,3-di(methylthio)acryloyl]ureas 6a,b in 85–88% yields. Cyclization of 6a,b in acetic acid containing methanesulfonic acid followed by oxidation with 3-chloroperoxybenzoic acid gave high yields of 1-alkoxy-5-alkyl-6-(methylsulfonyl)uracils 9a,b. Nucleophillic addition-elimination reaction of 9a,b with sodium azide, phenylthiol, or phenylselenol produced 6-azido-1-butoxythymine ( 2a , 98%), 5-ethyl-1-(2-phenoxyethoxy)-6-(phenylthio)uracil ( 2b , 95%), or 5-ethyl-1-(2-phenoxyethoxy)-6-(phenylselenenyl)uracil ( 2c , 91%).     

Synthesis of 1-substituted 2, 5-bischloromethylpyrrolidines

A number of 1-substituted 2, 5-bischloromethylpyrrolidines, cyclic analogs of bis-Β-chloroethylamine, have been synthesized. The previously unreported 1-phenyl- and 1-benzyl-2, 5-bis(N-cycloalkylaminomethyl)pyridines and their methiodides have been obtained.     

5- and 7-substituted 2-methyl-8-quinolinols

The synthesis and characterization of the 5- and 7-monosubstituted 2-methyl-8-quinolinols where the substituents are fluorine, chlorine, bromine, iodine, nitro, amino, and sulfonic acid groups were carried out. The bischelates with copper(II) of those ligands containing hydrogen, fluorine, chlorine, bromine, iodine, and nitro are also reported.     

3-N-乙酰基-2-取代芳基-5-[5'-甲基-异噁唑-3']-Δ3-1,3,4－噁唑啉类化合物的合成

甲基-异噁唑甲酰肼;3-N-乙酰基-2-取代芳基-5-[5'-甲基-异噁唑-3']-Δ3-1;3;4－噁唑啉类化合物的合成