3′-Amino-5′-carboxymethyl-3′,5′-dideoxy nucleosides for the synthesis of fully amide-linked RNA mimics

A convenient protocol is developed for the synthesis of 3′-[N-(fluorenylmethoxycarbonyl)-amino]-5′-carboxymethyl derivatives of all four natural ribonucleosides from cheap chiral pool compound glucose. Synthesis of fully amide-linked RNA analogues of small oligonucleotides containing, for the first time, all four nucleoside amino acids using standard solid phase Fmoc-chemistry is described.     

Solid-phase synthesis of 3-amino-1,2,4-triazoles

A solid-phase synthesis of 3-amino-1,2,4-triazoles is described. Reaction of resin bound S-methylisothiourea 2 with carboxylic acids yielded resin-bound S-methyl-N-acylisothioureas 3, which reacted with hydrazines under mild conditions to afford the corresponding resin-bound 3-amino-1,2,4-triazoles 4 with regioselectivity. Following cleavage, the desired products 5 were obtained in good yields and purities.     

A new scheme for the mechanism of Fischer indolization of arylhydrazones

A new scheme for the mechanism of Fischer indolization of arylhydrazones has been suggested based on quantum-chemical calculations by the MNDO AM1 method.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 961–962, May, 1994.     

A new synthesis of 4-oxygenated β-carboline derivatives by Fischer indolization

A new and short synthetic route to the 4-methoxy-β-carboline skeleton is described. The route involves Fischer indolization of enehydrazine of 1-tosylpiperidine-3,5-dione and successive acetalization-elimination for aromatization of 1,2,3,4-tetrahydro-2-tosyl-9H-β-carbolin-4-one. This method is efficiently applicable to synthesis of the benzene-part substituted 4-oxygenated β-carboline derivatives.     

Synthetic studies towards dendridine A: synthesis of hemi-dendridine A acetate by Fischer indolization

A short synthesis of hemi-dendridine A acetate has been accomplished. The synthesis is based on a modified Fischer indolization that represents a rare example of the single-step synthesis of a 7-oxytryptamine from an ortho-oxygenated phenylhydrazine. The synthetic route required developing an efficient synthesis of N-acetyl-2-pyrroline, the key coupling partner for the modified Fischer indolization. Some interesting chemistry associated with the abnormal Fischer indolization has been uncovered, whereby two molecules of the phenylhydrazine substrate combined along the abnormal reaction pathway, affording an unusual N-phenylindoleamine product.     

Solid-phase synthesis of substituted 1,3,4-thiadiazoles

Two novel and facile syntheses strategies for the synthesis of substituted 1,3,4-thiadiazoles on solid support are described based on a resin-bound thiosemicarbazide: (a) treatment with aldehydes to form immobilised thiosemicarbazones, and oxidative cyclodehydration with iron(III) chloride forms resin-bound 1,3,4-thiadiazoles; and (b) treatment with di-(2-pyridyl)thionocarbonate affords immobilised 1,3,4-thiadiazole-2-thione which is selectively mono-S-alkylated to yield resin-bound 2-alkylthio-1,3,4-thiadiazoles. Acidic cleavage with trifluoroacetic acid yields the products from both studies in good yield and excellent purity.     

A convenient synthesis of substituted 2,2′:6′,2″-terpyridines

The 2,2′:6′,2″-terpyridines 8a and 8b were prepared in good yield by reacting α-acetoxy-α-chloro-β-keto-esters 1 (R¹ = ⁿPr and Ph) with the bis-amidrazone 7 and 2,5-norbornadiene 5 in ethanol at reflux.     

A convenient synthesis of substituted 2,2′:6′,2″-terpyridines

The 2,2′:6′,2″-terpyridines 7a-c were prepared in good yield by reacting α-acetoxy-α-chloro-β-keto-esters 3a-c with bis-amidrazone 4 and 2,5-norbornadiene 6 in ethanol at reflux. Compounds 3a and 3b gave the 2,2′:6′,2″-terpyridines 9a and 9b, respectively, in moderate yield when treated with compound 4 and enamine 8.     

Microwave-assisted one-pot synthesis of substituted tetrahydrocarbazole and 8,9,10,11-tetrahydro-7H-pyrido[a]carbazoles

One-pot synthesis of one-substituted tetrahydrocarbazole and 4-substituted 8,9,10,11-tetrahydro-7H-pyrido[a]carbazoles from substituted quinolinylhydrazines and cyclohexanone in acetic acid was performed by microwave irradiation in a controlled temperature with simultaneous cooling system in closed vessel. The optimization procedures of process variables, power, temperature, and irradiation time are reported in detail, and the results from microwave processes are compared with conventional ones.     

Application of ring-rearrangement metathesis in organic synthesis: A grand design

In this report, we compiled various strategies involving a ring-rearrangement metathesis as a key step to assemble diverse molecules. Popular name reactions such as Grignard reaction, Overman rearrangement, Fischer indolization, Beckmann rearrangement and Diels–Alder reaction were used in combination with ring-rearrangement metathesis to construct complex targets. Additionally, CH activation and RRM strategy has been used to assemble azacycles. In some instances, the ring-rearrangement metathesis was expected to occur; however, ring-opening metathesis products were realized. These methods were included in the miscellaneous section. We anticipate that the lessons learned here are useful in designing complex polycyclic and heterocyclic targets suitable for biological and material science applications. Beside our work, we have also included others work as a background information.     

One-pot synthesis of substituted 3-amino-2-nitrothiophenes and selenophenes

In this work, we described an easy preparation of substituted 3-amino-2-nitrothiophenes and selenophenes. Substituted β-chloroacrylonitriles were reacted with sodium sulfide or sodium selenide and bromonitromethane to yield the expected compounds in a one-pot three-step procedure in good yields.     

Solid-phase synthesis of asymmetrically substituted "AB3-type" phthalocyanines

Synthesis of phthalocyanines with asymmetrical substitution on the periphery is often difficult due the problems in purification of the phthalocyanine mixtures obtained. Using a poly(ethylene glycol) (PEG)-based support with a Wang-type linker, we have developed the synthesis of monohydroxylated, oligoethylene glycol substituted phthalocyanines utilizing an amidine-base-promoted phthalonitrile tetramerization reaction. The use of a hydrophilic support allows symmetrical phthalocyanine product formed in solution to be readily and completely removed by washing while leaving the "AB3" product on the support. Acid cleavage with 10% trifluoroacetic acid provides the pure unsymmetrically substituted Pc. This method was applied to several metallo Pcs. Additionally, methods to avoid premature reactions on-resin that give A2B2 products are provided.     

Solid-phase synthesis of quinoxaline, thiazine, and oxazine analogs through a benzyne intermediate

A solid-phase synthetic route to quinoxaline, thiazine, and oxazine analogs is described. N-Alloc-3-amino-3-(2,4-difluoro-5-nitrophenyl)propanoic acid was tethered to Rink resin via its carboxylic acid group. The 4-arylfluorine was displaced with a primary amine, alcohol, or thiol to create, respectively, a resin bound aniline, phenol, or thiophenol derivative with one diversity element and one single atom (e.g., N, S, or O) diversity point. A fused heterocyclic system was subsequently created via a benzyne heterocyclization initiated by dehydrofluorination with strong base. Acid treatment released the desired products in high yield and moderate purity.     

Solid-phase synthesis of （Z）-allyl iodides from 3-acetoxy-2-methylene-alkanoates with recyclable polymer-supported selenium bromide

Reaction of polystyrene-supported lithium selenide with 3-acetoxy-2-methylene-alkanoates afforded the corresponding allyl selenide resins and subsequent cleavage from the polymer by treating with methyl iodide to furnish(Z)-allyl iodides in good yields and high purities.The polymeric selenium reagent can be regenerated and reused.So it is a environmentally benign reagent.     

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.     

Enantioselective synthesis of homocarbocyclic-2′-oxo-3′-azanucleosides

The enantioselective synthesis of homocarbocyclic-2′oxo-3′-azanucleosides has been performed by cycloaddition reaction of the N-glycosyl nitrones with allyl nucleobases. The use of nitrones originated from two different carbohydrates, the N-ribosyl nitrone and the N-mannosyl nitrone, proceeded in a stereocontrolled and predictable manner with a good degree of enantioselectivity, so allowing an easy entry to both enantiomers.     

Synthesis of a novel bridged nucleoside bearing a fused-azetidine ring, 3′-amino-3′,4′-BNA monomer

A novel bridged nucleic acid monomer, 3′-amino-3′-deoxy-5-methyl-3′-N,4′-C-methyleneuridine, was successfully synthesized via a useful and convenient azetidine ring formation under Staudinger's conditions. A ¹H NMR experiment and a PM3 calculation revealed that the sugar moiety of the novel bridged nucleic acid monomer, 3′-amino-3′,4′-BNA, was restricted to S-type conformation.     

Multicomponent reactions for the synthesis of new 3′-indolyl substituted heterocycles under microwave irradiation

A series of polysubstituted (3′-indolyl)pyrazolo[3,4-b]pyridine and (3′-indolyl)benzo[h]quinoline derivatives were synthesized via one-pot multicomponent reactions of aldehydes, 3-cyanoacetyl indoles with 5-aminopyrazol or naphthylamine under microwave irradiation. Particularly valuable features of this method include high yields of products, broad substrate scope, short reaction time and straightforward procedure.     

A facile synthesis of novel 2-amino-6-arylmethyl-7-carboxamido-7,8-dihydropyrimido[5,4-f][1,4]thiazepin-5-ones

A facile synthesis of novel 2-amino-6-arylmethyl-7-carboxamido-7,8-dihydropyrimido[5,4-f][1,4]thiazepin-5-ones is described. The synthesis was developed on solid phase and was applied to provide a series of analogs in good yield. The key reactions are acylation of a cysteine derivative with 2,4-dichloropyrimidine-5-carbonyl chloride followed by cyclization to generate a 6-arylmethyl-7-carboxamido-2-chloro-7,8-dihydropyrimido[5,4-f][1,4]thiazepin-5-one, which is further derivatized with an amine to give the desired 2-amino-6-arylmethyl-7-carboxamido-7,8-dihydropyrimido[5,4-f][1,4]thiazepin-5-one.     

Solid-phase synthesis of biarylalanines via Suzuki cross-coupling and intramolecular N-acyliminium Pictet-Spengler reactions

Solid-supported masked peptide aldehydes containing 3- or 4-iodophenylalanine residues were subjected to Pd-catalyzed Suzuki cross-coupling reactions with arylboronic acids. The biarylalanines generated were applied in intramolecular N-acyliminium Pictet-Spengler reactions. In this way, a range of pharmacologically interesting aryl-substituted pyrroloisoquinolines was obtained in excellent purity (>95%).