Regioselective synthesis of 6-alkylated lumazine derivatives

The regiospecific synthesis of alkylated lumazines is achieved by hetero Diels-Alder addition between an oxadiazinone 2 and enamine. The reactions proceed stepwise by cycloaddition, decarboxylation and deamination to produce the 6-alkylated lumazines.     

A new synthesis of anthyridine derivatives

An Ullmann reaction between 2-bromonicotinic acid and 2,6-diaminopyridine gave 6 -amino-2,2 -dipyridylamino-3-carboxylic acid (V). The latter was converted into 7-amino-5H-dipyrido-[1,2-a:2,3 -d]pyrimidin- 5-one (VII) by heating with polyphosphoric acid and into 2-amino-5,10 H-anthyridin-5-one (VIII) by heating with concentrated sulfuric acid. Structure proofs of VII and VIII are given and some derivatives of VIII are described.     

A novel synthesis of theophylline derivatives

Treatment of 6-amino-5-arylazo-1,3-dimethyluracils with ethyl propiolate gave the corresponding Michael-type adducts, 5-arylazo-1,3-dimethyl-6-ethoxycarbonylvinylaminouracils, which on treatment with a mixture of hydrochloric acid and acetic acid caused the acid-catalyzed rearrangement accompanied with rearrangement to give rise to the corresponding 8-anilinomethyltheophylline derivatives. In the case that the arylazo group possesses an electron-releasing substituent such as methoxy, the reaction proceeded in a different way to afford 1,2-bis(theophyllin-8-yl)ethane. The presumable reaction mechanisms for the above purine syntheses were proposed.     

A novel synthesis of coumarin derivatives

The chemical behaviors of 3-ethynylcoumarin towards benzyl bromide,diazonium chic ride,hydrogen chloride,ethyl magnesium bromide and its self-coupling are reported.     

A synthesis of 2-fluoroglucal derivatives

3,4,6-Tri-O-methyl-d-glucal, readily prepared from 3,4,6-tri-O-acetyl-d-glucal, undergoes lithiation at −78 °C in THF with t-BuLi to afford a vinyl carbanion, which can be trapped with electrophiles in moderate overall yields. The palladium coupling and Dötz-type reactions of these intermediates are also described.     

Ruthenium complexes with lumazine derivatives: structural,electrochemical, computational and radical scavenging studies

In this research study, the formation and characterization of new ruthenium(II) and (III) complexes encompassing multidentate ligands derived from 6-acetyl-1,3,7-trimethyllumazine (almz) are reported. The 1:1 molar coordination reactions of trans-[RuCl₂(PPh₃)₃] with N-1-[1,3,7-trimethyllumazine]benzohydride (bzlmz) and 6-(N-methyloxime)-1,3,7-trimethyllumazine (ohlmz) formed a diamagnetic ruthenium(II) complex, cis-[RuCl₂(bzlmz)(PPh₃)] (1), and paramagnetic complex, cis-[Ru^IIICl₂(olmz)(PPh₃)] (2) [Holmz = 6-(N-hydroxy-N′-methylamino)-1,3,7-trimethyllumazine], respectively. These ruthenium complexes were characterized via physico-chemical and spectroscopic methods. Structural elucidations of the metal complexes were confirmed using single crystal X-ray analysis. The redox properties of the metal complexes were investigated via cyclic voltammetry. Electron spin resonance spectroscopy confirmed the presence of a paramagnetic metal centre in 2. The radical scavenging activities of the metal complexes were explored towards the DPPH and NO radicals. Quantum calculations at the density functional theory level provided insight into the interpretation of the IR and UV–Vis experimental spectra of 1.     

A novel synthesis for quinoline derivatives

Condensation of ethyl 2-(2-oxo-2,3-dihydro-1H-indolid-3-ene)cyanoacetate and/or 2-(2-oxo-2,3-dihydro-1H-indolid-2-ene)malononitrile with 3-methylpyrazolin-5-one, 1-phenyl-3-methyl-pyrazolin-5-one, benzoyl acetonitrile or ethyl acetoacetate affords different substituted quinolines. The reaction is suggested to proceed through a nucleophilic addition followed by ring opening and recyclization steps.     

A convenient synthesis of 3,3,3-trifluoroalanine derivatives

A one-pot synthesis of N-substituted 3,3,3-trifluoroalanine esters from alkyl trifluoropyruvates and carboxamides or substituted ureas was developed.     

A convenient synthesis of 2,4-diaminoquinoline derivatives

Base or Lewis acid induced cyclisation of the o-amidinobenzonitriles (III) provides 2,4-diaminoquinoline derivatives (IV) in high yield.     

A concise enantioselective synthesis of iminosugar derivatives

The concise de novo synthesis of amino- and iminosugar derivatives is presented; the four stereocenters of the iminosugar derivatives are created in two-steps with high chemoselectivity and excellent enantioselectivity.     

A convenient one-step synthesis of fluoroethylidene derivatives

A convenient one-step synthesis of gem-monofluoroalkylolefins starting from aldehydes or ketones was developed. This method comprises the utilisation of 2-(1-fluoroethyl)sulfonyl-1,3-benzothiazole according to Julia's procedure and opens a new opportunity for the synthesis of fluoroalkylidene derivatives.     

A new palladium-catalyzed synthesis of indoxyl derivatives

The reaction of iodoanilines with phenylacetylene and carbon monoxide catalyzedby a palladium(0) catalyst leads to indoxyl derivatives.     

A convenient synthesis of tricyclic purine derivatives

A convenient synthesis of new heterocycles such as 7,8-dihydro-1H-imidazo[2,1-i]purin-5(4H)-ones ( 2 , n = 0) and 5,6-dihydro-1H-imidazo[2,1-b]purin-9(8H)-ones ( 3 ) was described. The syntheses of 2 and 3 were accomplished by treatment of 6-methylthio-7H-purin-2(3-H)-ones 7 or 2-benzylthio-1-methyl-9-triphenylmethyl-9H-purin-6(1H)-one ( 15 ) with appropriate aminoalcohol followed by dehydrative cyclization using thionyl chloride. Compound 15 was efficiently prepared by benzylation of 6-hydroxy-2-mercaptopurine ( 12 ) followed by tritylation and N-methylation.     

A two-step practical synthesis of dehydroalanine derivatives

A two-step practical synthesis of dehydroalanine derivatives from commercially available starting materials is reported. The approach comprises an Ugi four-component reaction using 2-benzoylacetaldehyde, followed by an elimination process of the benzoate group. This protocol provided access to several dehydroalanine derivatives modified with diverse functional groups, which might be useful for further transformations in the construction of more complex molecules.     

A convenient synthesis of 8-oxoprotoberberine derivatives

The annulation of isoquinoline derivatives to form the 8-oxoprotoberberine derivatives is described. The key step of the reaction involves intramolecular alkylation of the Reissert compounds.     

Design, synthesis, and evaluation of acyclic C-nucleoside and N-methylated derivatives of the ribitylaminopyrimidine substrate of lumazine synthase as potential enzyme inhibitors and mechanistic probes

Lumazine synthase and riboflavin synthase catalyze the last two steps in the biosynthesis of riboflavin, a vitamin that is involved in many critical biochemical reactions that are essential for the maintenance of life. To obtain inhibitors and structural probes that could be useful in studying the structures of bound reaction intermediates, the ribitylamino N-H moiety of the lumazine synthase substrate was replaced by CH(2) and N-CH(3) groups. The CH(2) replacement unexpectedly and completely abolished the affinity for lumazine synthase, thus revealing a critical, yet unexplained, role of the ribitylamino N-H moiety in conferring affinity for the enzyme. In contrast, the N-CH(3) replacement resulted in an inhibitor of both lumazine synthase and riboflavin synthase. Replacement of the ribitylamino N-H moiety with epimeric C-F moieties led to inhibition of lumazine synthase and riboflavin synthase when combined with the replacement of the 5-amino group with a nitro substituent.     

A metastable prerequisite for the growth of lumazine synthase crystals

Dense liquid phases, metastable with respect to a solid phase, form in solutions of proteins and small-molecule materials. They have been shown to serve as a prerequisite for the nucleation of crystals and other ordered solid phases. Here, using crystals of the protein lumazine synthase from Bacillus subtilis, which grow by the generation and spreading of layers, we demonstrate that within a range of supersaturations the only mechanism of generation of growth layers involves the association of submicrometer-size droplets of the dense liquid to the crystal surface. The dense liquid is metastable not only with respect to the crystals, but also with respect to the low-concentration solution: dynamic light scattering reveals that the droplets' lifetime is limited to several seconds, after which they decay into the low-concentration solution. The short lifetime does not allow growth to detectable dimensions so that liquid-liquid phase separation is not observed within a range of conditions broader than the one used for crystallization. If during their lifetime the droplets encounter a crystal surface, they lower their free energy not by decay, but by transformation into crystalline matter, ensuring perfect registry with the substrate. These observations illustrate two novel features of phase transformations in solutions: the existence of doubly metastable, short-lifetime dense phases and their crucial role for the growth of an ordered solid phase.