Simple and efficient method for the synthesis of 2′,3′-didehydro-3′-deoxythymidine (d4T)

2′,3′-Didehydro-3′-deoxythymidine (d4T) is an orally active antiviral drug used in the treatment of AIDS. A novel two-step synthetic method was developed for the synthesis of d4T using inexpensive reagents. An improvement in the yield was achieved for the conversion of the intermediate oxetane to d4T. This is the first simple and efficient method for the large-scale synthesis of d4T.     

A new, facile, and protection-free one-pot chemical synthesis of 2′-deoxynucleoside-5′-tetraphosphates

A new straight forward, reliable, and an efficient method for the chemical synthesis of 2′-deoxynucleoside-5′-tetraphosphate is reported. The present ‘one-pot, three step’ synthetic strategy involves the monophosphorylation of nucleoside followed by reaction with tris-(tri-n-butylammonium) triphosphate and hydrolysis of the putative cyclic tetrametaphosphate intermediate to provide the corresponding 2′-deoxynucleoside-5′-tetraphosphate in moderate yield with high purity.     

Concise and efficient synthesis of 3′-O-triphosphates of 2′-deoxyadenosine and 2′-deoxycytidine

We describe concise and efficient synthesis of 2′-deoxyadenosine-3′-O-triphosphate (2′-d-3′-ATP) and 2′-deoxycytidine-3′-O-triphosphate (2′-d-3′-CTP) which are well known for their various biological applications. One-pot synthetic methodology was used to convert N⁶-Benzoyl-5′-O-levulinoyl-2′-deoxyadenosine into N⁶-Benzoyl-5′-O-levulinoyl-2′-deoxyadenosine-3′-O-triphosphate in 72% yield. One-step concurrent deprotection of N⁶-Benzoyl and 5′-O-levulinoyl groups using concentrated aqueous ammonia resulted in 2′-d-3′-ATP in 75% yield. The same synthetic strategy was successfully employed to convert N⁴-Benzoyl-5′-O-levulinoyl-2′-deoxycytidine into 2′-d-3′-CTP in 66% yield.     

A facile synthesis of fused aromatic spiroacetals based on the 3,4,3′,4′-tetrahydro-2,2′-spirobis(2H-1-benzopyran) skeleton

The facile synthesis of a series of aromatic 6,6-spiroacetals based on the parent 3,4,3′,4′-tetrahydro-2,2′-spirobis(2H-1-benzopyran) heterocyclic system is reported. Key steps included the use of a Sonogashira coupling for the synthesis of an aryl acetylene that was coupled to an aryl aldehyde to form a propargyl alcohol intermediate. Hydrogenation of the alkynol followed by oxidation produced a masked dihydroxy ketone that upon treatment with trimethylsilyl bromide underwent deprotection and cyclisation to the fused aromatic spiroacetal.     

Synthesis of 3′-deoxy-3′-C-methyl-β-d-ribonucleoside analogs

3′-Deoxy-3′-C-methyl-β-d-ribonucleoside analogs bearing the five canonical bases of nucleic acids have been synthesized. All these derivatives were prepared by glycosylation of the corresponding heterocyclic bases with a suitable peracylated 3-C-methyl sugar precursor. The synthesis of the 3-C-methyl sugar precursor is described following a new stereoselective synthetic pathway.     

5,5′-二甲基-2,2′-二茚满-1,1′,3,3′-四酮的合成及结构表征

本文以4-甲基邻苯二甲酸酐为原料, 成功地合成了5,5′-二甲基-2,2′-二茚满-1,1′,3,3′-四酮(2). 通过元素分析、核磁共振、红外光谱及质谱等测试手段, 确定了化合物2的结构与存在形式, 通过ESR测试发现化合物2具有顺磁性.     

A practical synthesis of 2′-aminoacylamino-2′-deoxyadenosines

A practical and efficient synthesis of 2′-aminoacylamino-2′-deoxyadenosine derivatives is reported. EDCI/HOBt-mediated coupling of a 3′,5′-diprotected 2′-amino-2′-deoxyadenosine derivative to various N-Cbz-l-amino acid derivatives followed by global deprotection affords analytically pure 2′-aminoacylamino-2′-deoxyadenosine derivatives without the necessity for preparative HPLC purification. These compounds are non-hydrolysable isosteres of 2′-aminoacyladenosines, which are of use in X-ray studies for the elucidation of the editing mechanism of various tRNA synthetases.     

One-pot synthesis of 5,5′-dibromo-2,2′-dipyridylacetylene and its boronic acid derivative

5,5′-Dibromo-2,2′-dipyridylacetylene was prepared from 2,5-dibromopyridine and (trimethylsilyl)acetylene via the new one-pot synthesis approach using a regioselective palladium-catalyzed coupling reaction with a 60% yield. Several protocols of lithium-halogen exchange were then attempted to synthesize 6,6′-(1,2-ethynediyl)bis[3-pyridylboronic acid] from 5,5′-dibromo-2,2′-dipyridylacetylene. The former was successfully obtained with a 54% yield by a reverse addition method using toluene and THF and it showed potential as a useful building block for cross-coupling reactions in the formation of carbon-carbon bonds.     

An efficient synthesis of new 1-H-4′-methyl-3′,4′-dihydrospiro[piperidine-4,2′(1′H)quinoline] scaffolds

Efficient synthesis of new 3′,4′-dihydrospiro[piperidine-4,2′(1′H)quinolines] by a four step synthetic route based on 1-benzyl-4-piperidone reactivity is reported.     

Acid-catalyzed condensation of 2,2′-diamino-1,1′-biaryls for the synthesis of benzo[c]carbazoles

2,2′-Diamino-1,1′-biaryls were found to undergo ring-closure condensation reaction to afford benzo[c]carbazoles in good to excellent yield. Coupled with the synthesis of 2,2′-biaryldiamines from diaryl hydrazides via [3,3]-sigmatropic rearrangement, it constitutes a new efficient synthetic method for benzo[c]carbazoles and related compounds.     

New reagent for the preparation of oligonucleotides involving a 5′-thiophosphate or a 5′-phosphate group

We report here a novel, simple reagent enabling the chemical incorporation of a thiophosphate or a phosphate group at the 5′-end of oligonucleotides using very mild basic deprotection conditions. This method can be useful in the case of alkali sensitive modified oligonucleotides. This reagent also gives access to the preparation of bifunctional oligonucleotides with either a thiophosphate group at the 5′-end and a phosphate at the 3′-end, or two thiophosphate groups at both the 5′- and the 3′-ends, or a 5′-thiophosphate group and a 3′-amino-containing linker.     

Scandium triflate-catalyzed 6,6′-diiodination of 2,2′-dimethoxy-1,1′-binaphthyl with 1,3-diiodo-5,5-dimethylhydantoin

Scandium triflate-catalyzed iodination of 2,2′-dimethoxy-1,1′-binaphthyl with 2 equiv of 1,3-diiodo-5,5-dimethylhydantoin (DIH) proceeded to give 6,6′-diiodo-2,2′-dimethoxy-1,1′-binaphtyl in 98% yield and subsequent deprotection of methyl groups provided 6,6′-diiodo-1,1′-binaphthol, which is a useful ligand or reagent for many enantioselective transformations. Use of 2 equiv of NIS in place of DIH in the presence of scandium triflate, however, did not successfully yield 6,6′-diiodo-2,2′-dimethoxy-1,1′-binaphtyl, indicating that one of two types of iodine atoms in DIH is more reactive toward the iodination than iodine in NIS.     

Stereoselective synthesis of (1′S,3R,4R)-4-acetoxy-3-(2′-fluoro-1′-trimethylsilyloxyethyl)-2-azetidinone

A stereoselective synthesis of (1′S,3R,4R)-4-acetoxy-3-(2′-fluoro-1′-trimethylsilyloxyethyl)-2-azetidinone as a new fluorine-containing intermediate towards β-lactams, is described. The synthetic key step relies upon the dynamic kinetic resolution (DKR) of ethyl 2-benzamidomethyl-4-fluoro-3-oxo-butanoate via asymmetric transfer hydrogenation catalyzed by [Ru(η⁶-arene)(S,S)-R₂NSO₂DPEN].     

Chiral syntheses of 6′-β-fluoroaristeromycin, 6′-β-fluoro-5′-noraristeromycin and aristeromycin

Carbocyclic nucleosides substituted at the C-6′ position are receiving increasing attention. Chiral synthetic accessibility to the biologically promising 6′-β-fluoroaristeromycin is lacking. Its preparation and that of the 5′-nor analogue are described. Along the way, a new method to aristeromycin arose as an outgrowth of a requisite structure proof.     

Improved synthesis of 4,4′-diamino-2,2′-bipyridine from 4,4′-dinitro-2,2′-bipyridine-N,N′-dioxide

A superior synthetic route to 4,4′-diamino-2,2′-bipyridine has been developed. This procedure compares favorably with existing methods, producing 4 times the yield previously reported. In addition, mild reaction conditions are utilized, allowing a considerably more efficient production, and subsequent purification, of the diamino complex.     

New and efficient synthesis of 5′-amino-5′-(S)-methyl-2′,5′-dideoxynucleosides

A short, efficient synthesis of 5′-amino-5′-(S)-methyl-2′,5′-dideoxynucleosides 1 has been developed through the diastereoselective addition of methylmagnesium bromide or methyllithium to an intermediate tert-butylsulfinimide.     

Reactivity between acetone and single-stranded DNA containing a 5′-capped 2′-fluoro-N7-methyl guanine

DNA-mediated catalysis is an emerging field in bioorganic chemistry and chemical biology. However, the functional group diversity and known reactivity of DNA (A, T, C, and G) is relatively limited in scope. This relatively defined reactivity can limit the utility of DNA as a catalyst. In an effort to expand the functional group diversity and chemical reactivity of DNA, we sought to explore reactions involving single-stranded DNA equipped with a stabilized variant of N7-methyl guanine (2′-fluoro-5′-N7-methyl guanine). Here, we show that 5′-capped 2′-fluoro-N7-methyl guanine-labeled single-stranded DNA reacts with a ketone to afford a ketone-labeled DNA. This reaction likely proceeds through a reactive ylide or N-heterocyclic carbene. Taken together, our findings suggest that 2′-fluoro-5′-N7-methyl guanine is a stable adduct that can be selectively incorporated into ssDNA and functionalized with a ketone moiety by reaction with a simple ketone. Incorporation of this nucleoside into ssDNA may be useful for the evolution of novel deoxyribozymes that catalyze new reactions, including those which proceed via a reactive ylide or N-heterocyclic carbene-mediated chemistry.     

Regiodirected phosphorylation of 2,2′,7,7′-tetrahydroxydinaphthylmethane

The phosphorylation of 2,2′,7,7′-tetrahydroxydinaphthylmethane was studied and the influence of molecule pre-organization on the regioselectivity of functionalization was investigated. The reactions of 2,2′,7,7′-tetrahydroxydinaphthylmethane with phosphorous amides containing 1-3 amide bonds gave oligophosphorylated derivatives differing in the number and the nature of phosphorus fragments and in the size of phosphorus rings: tetraphosphorus macrocycles containing one 24-membered and two eight-membered phosphorus rings, triphosphorus compounds containing a phosphocine ring and two acyclic phosphorus fragments, and tetraphosphorylated derivatives with four phosphorus groups in the molecule. The possibility of controlling the regioselectivity of phosphorylation by using reagents differing in the number and activity of P-N bonds was demonstrated.     

Synthesis of 2′,3′-dideoxy-6′,6′-difluoro-3′-azanucleosides

The straightforward synthesis of four novel 2′,3′-dideoxy-6′,6′-difluoro-3′-azanucleosides 1a-d is described. Efficient construction of the fluorine-containing pyrrolidine ring through two different ways and installation of pyrimidine rings using the amino groups in the intermediates 12, 26 were the key steps of our synthesis.