Synthesis and Incorporation of k2U into RNA

Lysidine (k²C) is one of the most modified pyrimidine RNA bases. It is a cytidine nucleoside, in which the 2-oxo functionality of the heterocycle is replaced by the ϵ-amino group of the amino acid lysine. As such, lysidine is an amino acid-containing RNA nucleoside that combines directly genotype (C-base) with phenotype (lysine amino acid). This makes the compound particularly important in the context of theories about the origin of life and here especially for theories that target the origin of translation. Here, we report the total synthesis of the U-derivative of lysidine (k²U), which should have the same base pairing characteristics as k²C if it exists in the isoC-like tautomeric form. To investigate this question, we developed a phosphoramidite building block for k²U, which allows its incorporation into RNA strands. Within RNA, k²U can base pair with the counter base U and isoG, confirming that k²U prefers an isoC-like tautomeric structure that is also known to dominate for k²C. The successful synthesis of a k²U phosphoramidite and its use for RNA synthesis now paves the way for the preparation of a k²C phosphoramidite and RNA strands containing k²C.     

Amino Acid Modified RNA Bases as Building Blocks of an Early Earth RNA-Peptide World

Fossils of extinct species allow us to reconstruct the process of Darwinian evolution that led to the species diversity we see on Earth today. The origin of the first functional molecules able to undergo molecular evolution and thus eventually able to create life, are largely unknown. The most prominent idea in the field posits that biology was preceded by an era of molecular evolution, in which RNA molecules encoded information and catalysed their own replication. This RNA world concept stands against other hypotheses, that argue for example that life may have begun with catalytic peptides and primitive metabolic cycles. The question whether RNA or peptides were first is addressed by the RNA-peptide world concept, which postulates a parallel existence of both molecular species. A plausible experimental model of how such an RNA-peptide world may have looked like, however, is absent. Here we report the synthesis and physicochemical evaluation of amino acid containing adenosine bases, which are closely related to molecules that are found today in the anticodon stem-loop of tRNAs from all three kingdoms of life. We show that these adenosines lose their base pairing properties, which allow them to equip RNA with amino acids independent of the sequence context. As such we may consider them to be living molecular fossils of an extinct molecular RNA-peptide world.     

Regioselective synthesis of N(3)‐ and O‐acylmethyl derivatives of 2‐methylthio‐4(3H)‐quinazolinone

Reaction of 2‐methylthio‐4(3H)‐quinazolinone with chloroacetone, ω‐bromoacetophenone or ethyl bromoacetate in different solvents (methanol, acetonitrile, dimethylformamide and toluene) using sodium methoxide or potassium carbonate as a base were studied. Regioselective N₍₃₎‐alkylation took place in toluene using potassium carbonate, whereas in dimethylformamide O‐acylmethyl derivatives were obtained. However chloroacetone reacted with 2‐methylthio‐4(3H)‐quinazolinone under various conditions to give a mixture of N₍₃₎/O‐isomers.     

Reactions of 5-(6-Methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,3,4-oxadiazole-2-thione with Electrophiles

 Treatment of 5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,3,4-oxadiazole-2-thione with haloalkanes yielded oxadiazole S-alkyl derivatives, whereas its reaction with formaldehyde and amines resulted in formation of oxadiazole N(3)-aminomethyl derivatives. The alkylation of 2-alkylsulfanyl-5-(6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,3,4-oxadiazoles with methyl bromoacetate proceeded at the N(1)-position of pyrimidine to give 2-alkylsulfanyl-5-(1-methoxycarbonylmethyl-6-methyl-2,4-dioxo-1,2,3,4-tetrahydro-3-pyrimidinyl)-methyl-1,3,4-oxadiazoles, whereas aminomethylation, bromination, or nitration took place at position 5 of pyrimidine ring and afforded the corresponding 5-pyrimidine substituted derivatives.     

WO3 coatings for photoelectrochemical synthesis of persulfate: efficiency,stability and applicability

Journal of Solid State Electrochemistry - Light-assisted electrochemical processes have the potential to replace energy-intensive electrosynthesis technologies, especially in the area of strong...     

Synthesis and intramolecular cyclization of 2‐methylsulfany‐4‐oxo‐3(4H)‐quinazolinyl)acetohydrazide

Treatment of ambident sodium salt of 2‐methylsulfanyl‐4(3H)‐quinazolinone with methyl bromoacetate resulted in N₍₃₎‐alkyl ester formation. Reaction of the resulted ester with hydrazine hydrate gave 2‐methylsulfanyl‐4‐oxo‐3(4H)‐quinazolinyl)acetohydrazide, which underwent intramolecular cyclization under heating in dimethylformamide to give 1‐aminoimidazo[2,1‐b]quinazoline‐2,5(1H,3H)‐dione. The latter took place in acylation reaction and in condensation with aromatic aldehydes.     

Convenient way to 5‐substituted 4‐amino‐2,3‐dihydro‐4H‐1,2,4‐triazole‐3‐thiones

Various 4‐amino‐2,3‐dihydro‐4H‐triazoles with aromatic, aliphatic and heterocyclic substituents at the C(5) position were synthesized from corresponding esters and thiocarbohydrazide. This method allows the synthesis these heterocycles in a short time and at reduced expenses.     

Glycerol-1,2-carbonate: A mild reagent for the N-glycerylation of pyrazolecarboxylates

In this study, glycerol-1,2-carbonate was employed as a convenient reagent for the synthesis of more complex pyrazole-containing heterocyclic systems. 3-O-Tosylated glycerol-1,2-carbonate (TGC) was used for alkylation of NH-pyrazolecarboxylates. The obtained N-glycerylated pyrazoles were further treated with diverse nucleophiles for 2-oxo-1,3-dioxolane ring cleavage. The synthesized 1-(2,3-dihydroxypropyl)-1H-pyrazole-5-carboxylates were subsequently hydrolyzed and treated with p-toluenesulfonic acid, yielding a series of 6-(hydroxymethyl)-6,7-dihydro-4H-pyrazolo[5,1-c][1,4]ox-azin-4-ones.     

Synthesis of 2‐imino‐7‐methyl‐2,3‐dihydroimidazo[1,2‐a]‐pyrimidin‐5(1H)‐ones and their reactions with nucleophiles

[2‐Alkylthio‐6‐methyl‐4‐oxopyrimidin‐3(4H)‐yl]acetonitriles ( 3‐5 ) treated with sodium methoxide in methanol followed by ammonium chloride were cyclized to 2‐imino‐7‐methyl‐2,3‐dihydroimidazo[1,2‐a]‐pyrimidin‐5(1H)‐ones ( 6‐8 ). Under acid or base‐catalyzed hydrolysis they were converted to 7‐methyl‐imidazo[1,2‐a]pyrimidine‐2,5‐[1H,3H]‐diones ( 9‐11 ), whereas in the reaction with butyl‐ or benzylamine the corresponding 7‐methyl‐2‐(substitutedamino)imidazo[1,2‐a]pyrimidin‐5(3H)‐ones ( 13‐18 ) were produced. The latter were found to exist in two tautomeric forms in CDCl₃ solution.     

Sol–gel synthesis of calcium hydroxyapatite thin films on quartz substrate using dip-coating and spin-coating techniques

Sol–gel synthesis route was suggested to prepare calcium hydroxyapatite (Ca₁₀(PO₄)₆(OH)₂, CHA) thin films on quartz substrates. CHA thin films were obtained using dip-coating and spin-coating techniques by coating the substrates 1, 5, 15 and 30 times. In the sol–gel process, the ethylenediaminetetraacetic acid and 1,2-ethandiol as complexing agents were used. Moreover, triethanolamine and polyvinyl alcohol were used as gel network forming materials. After each coating procedure the films were annealed at 1,000 °C. The results obtained from dip-coating and spin-coating techniques were compared in this study. It was demonstrated, that the formation of calcium hydroxyapatite depends on dipping (or spinning) time and annealing duration.