One-pot synthesis of nucleoside 5'-triphosphates from nucleoside 5'-H-phosphonates

Nucleoside 5'-triphosphates (NTPs) play key roles in biology and medicine. However, these compounds are notoriously difficult to synthesize. We describe a one-pot method to prepare NTPs from nucleoside 5'-H-phosphonate monoesters via pyridinium phosphoramidates, and we used this approach to synthesize ATP, UTP, GTP, CTP, ribavirin-TP, and 6-methylpurine ribonucleoside-TP (6MePTP). Poliovirus RNA-dependent RNA polymerase efficiently employed 6MePTP as a substrate, suggesting that the cognate nucleoside, a poorly understood antiviral agent, may damage viral RNA.     

Convenient synthesis of nucleoside 5'-triphosphates for RNA transcription

By generating a selective phosphitylating reagent in situ, nucleoside 5'-triphosphates can be conveniently synthesized in one pot. This novel strategy without nucleoside protection has been developed to largely simplify synthesis of the nucleoside triphosphates. This demonstrated principle can be applied to the 5'-triphosphate synthesis of both native and modified nucleosides.     

Synthesis and properties of DNA oligomers containing 2'-deoxynucleoside N-oxide derivatives

Cytosine and adenine N-oxide derivatives have long been known as products resulting from the oxidative damage of DNA by peroxides such as hydrogen peroxide. Although the synthesis and properties of 2'-deoxynucleoside N-oxide derivatives have been well described, little has been reported about the chemical and biochemical behavior of initially formed DNA oligomers containing these N-oxide bases. In this study, we established a convenient method for the solid-phase synthesis of oligodeoxynucleotides incorporating 2'-deoxycytidine N-oxide (dC O) or 2'-deoxyadenosine N-oxide (dA O) by using the postsynthetic oxidation of N-protected DNA oligomers except for the target dC or dA site with m-CPBA in MeOH in a highly selective manner. In this strategy, the benzoyl, phthaloyl, and (4-isopropylphenoxy)acetyl groups proved to serve as base protecting groups to avoid oxidation of adenine, cytosine, and guanine, respectively, at the unmodified sites.     

Improved method for the solid-phase synthesis of oligoribonucleotide 5'-triphosphates

We have developed an improved solid-phase method for the synthesis of 5'-triphosphates (5'-TPs) of oligoribonucleotides. The method is based on the use of salicyl phosphorochloridite as the phosphitylating reagent and the improvement is characterized by the use of the highly reactive pyrophosphorylating reagent tris(tetra-n-butylammonium) hydrogen pyrophosphate instead of the conventional tri-n-butylammonium salt for the nucleophilic substitution reaction to form the cyclic ester intermediate. The improved method can be used to generate oligoribonucleotide 5'-TPs efficiently and reproducibly.     

Efficient one-pot synthesis of ethyl 2-substitued-4-methylthiazole-5-carboxylates

A new and practical one-pot procedure for the synthesis of several 2-sustituted-4-methylthiazole-5-carboxylates from commercially available starting materials is described. Under mild reaction conditions, some of the products with alkyl group on the 2-amino group or with various groups on 2-substituted phenyl ring were obtained in good yields from ethyl acetoacetate, N-bromosuccinimide, thiourea, or its N-substituted derivatives in an efficient way instead of the traditional two-step reaction.     

Facile one-pot synthesis of 5-substituted hydantoins

5-Substituted and 5,5-disubstituted hydantoins are synthesised from the corresponding aldehydes or ketones, using a one-pot, gallium(III) triflate-catalysed procedure that is compatible with a range of substrates and solvents.     

A three-component one-pot synthesis of 2-alkoxy-4-amino-N- arylthiazole-5-carboxamides

A facile and efficient protocol was developed to access 2-alkoxy-4-amino-N-arylthiazole-5-carboxamides through a three-component one-pot reaction, which involved potassium methyl cyanimidodithiocarbonate, 2-halo-N-arylacetamides and alcohols. The easy availability and the broad structural diversity of substrates make the reaction useful for the construction of libraries in drug discovery.     

Programmable one-pot multistep organic synthesis using DNA junctions

A system for multistep DNA-templated synthesis is controlled by the sequential formation of DNA junctions. Reactants are attached to DNA adapters which are brought together by hybridization to DNA template strands. This process can be repeated to allow sequence-controlled oligomer synthesis while maintaining a constant reaction environment, independent of oligomer length, at each reaction step. Synthesis can take place in a single pot containing all required reactive monomers. Different oligomers can be synthesized in parallel in the same vessel, and the products of parallel synthesis can be ligated, reducing the number of reaction steps required to produce an oligomer of a given length.     

Chemoselective one-pot synthesis of 2-phenylamino-5-alkylthio-1,3,4-thiadiazole derivatives from phenylthiosemicarbazide and CS2

A novel and fairly efficient chemoselective one-pot method has been developed for the synthesis of both 2-phenylamino-5-alkylthio-1,3,4-thiadiazole and bis-(2-phenylamino-5-alkylthio-)1,3,4-thiadiazole derivatives from phenylthiosemicarbazide and CS₂.     

Natural eutectic salts catalyzed one-pot synthesis of 5-arylidene-2-imino-4-thiazolidinones

The rapid, very simple and green one-pot synthesis of 5-arylidene-2-imino-4-thiazolidinones by condensation of the thioureas with chloroacetyl chloride and an aldehyde in natural deep eutectic solvent with good to excellent yields is described.     

Palladium-catalyzed one-pot synthesis of 2-alkyl-2-arylcyanoacetates

A one-pot procedure for the synthesis of 2-alkyl-2-arylcyanoacetates based on a Pd(OAc)2/DPPF (DPPF = 1,1'-diphenylphosphino ferreocene)-catalyzed enolate arylation followed by in situ alkylation has been developed. This procedure tolerates a diverse range of aryl and heteroaryl bromides, and provides a rapid entry to a variety of 2-alkyl-2-arylcyanoacetates in good to excellent yield.     

Solvent-free one-pot synthesis of 2-pyridone derivatives

An efficient synthesis of methyl 4-hydroxy-6-oxo-1,6-dihydro-2-pyridine carboxylates is described.This involves three component reactions between primary alkyl amines,malonyl dichloride and methyl propiolates.     

An effective one-pot synthesis of 5-substituted tetronic acids

An expeditious one-pot synthesis of 5-substituted tetronic acids from aldehydes and terminal conjugated alkyne as starting materials is described. The entire process embodies two consecutive chemical events: a catalytic domino reaction to build the 1,3-dioxolane scaffolds 5 and a two-step acid-catalyzed trans-acetalization-lactonization reaction to furnish the tetronic acid derivatives 6.     

Organocatalytic synthesis of N-Phenylisoxazolidin-5-ones and a one-pot synthesis of beta-amino acid esters

A novel N-heterocyclic carbene (NHC)-catalyzed C-N bond formation by the reaction of alpha,beta-unsaturated aldehydes and nitrosobenzene to N-phenylisoxazolidin-5-ones, followed by an acid-catalyzed esterification and Bamberger-like rearrangement in a mild one-pot protocol leads to N-p-methoxyphenyl (N-PMP) protected beta-amino acid esters.     

Diastereoselective one-pot synthesis of 7- and 8-substituted 5-phenylmorphans

Novel 7- and 8-alkyl and aryl substituted 5-phenylmorphans were synthesized from substituted allyl halides and N-benzyl-4-aryl-1,2,3,6-tetrahydropyridine by a highly efficient and diastereoselective reaction series, "one-pot" alkylation and ene-imine cyclization followed by sodium borohydride reduction. Mild cyclization conditions gave the desired substituted 5-phenylmorphans in good yield as a single diastereomer.     

BOP-mediated one-pot synthesis of C5-symmetric macrocyclic pyridone pentamers

We report here, for the first time, the BOP-mediated one-pot macrocyclization that is facilitated and guided by internally placed intramolecular H-bonds to allow for the highly selective formation of five-residue cation-binding macrocycles.     

Facile one-pot synthesis of N-difluoromethyl-2-pyridone derivatives

[reaction: see text] A novel one-pot synthesis of N-difluoromethyl-2-pyridones is described. N-(Pyridin-2-yl)acetamide derivatives were excellent precursors for the preparation of N-difluoromethyl-2-pyridone derivatives. Difluoromethylation of 2-acetaminopyridine derivatives was achieved with sodium chlorodifluoroacetate as a difluorocarbene source in the presence of a catalytic amount of 18-crown-6. Subsequent in situ hydrolysis of resultant 1,2-dihydro-2-acetimino-1-difluoromethylpyridines proceeded under mild acidic conditions to afford the corresponding N-difluoromethyl-2-pyridones in moderate to good yields.     

Rapid and straightforward one-pot expeditious synthesis of 2-amino-5-alkylidene-thiazol-4-ones at room temperature

A new methodology has been developed towards the room temperature synthesis of novel 2-amino-5-alkylidenethiazol-4-ones from aldehydes, amines and rhodanine in one-pot. A heterogeneous dipolar catalyst has been utilized for this reaction. The unique properties of this catalyst effectively synthesize such compounds at room temperature in contrast to all earlier reports.