Vibrational spectra and structure of the photochromic 2-(2′,4′-dinitrobenzyl)pyridine

The molecular structure of the pale yellow crystals of 2-(2′,4′-dinitrobenzyl)pyridine (CH₂ form) and its photo induced ‘enamine’ NH tautomer (dark blue crystals) have been studied by means of vibrational spectra and ab initio calculations. The Raman spectrum of the photo-sensitive CH₂ form was registered by NIR FT-Raman spectroscopy by means of the Nd:YAG laser as an excitation source. Ab initio calculations have been performed for the CH₂ and NH tautomers at the Hartree-Fock level using a 6-21G** basis set. The theoretical geometrical parameters for the isolated 2-(2′,4′-dinitrobenzyl)pyridine molecule (CH₂ form) are close to the literature X-ray diffraction data. According to the theory the dihedral angle between the benzene and pyridine ring planes in the NH photo induced tautomer is about 46°, the ortho-nitro group is twisted about 25° towards the benzene ring plane, whereas the para-nitro group is coplanar to the benzene ring. The assignment of the fundamental vibration frequencies of both 2-(2′,4′-dinitrobenzyl)pyridine tautomers CH₂ and NH have been performed on the basis of Raman and infrared spectra and ab initio force field calculations. The computed frequencies are in coincidence with the registered ones; the mean deviations are between 23.7 and 28.5 cm⁻¹.     

A ring-closing metathesis based synthesis of bicyclic nucleosides locked in S-type conformations by hydroxyl functionalised 3′,4′-trans linkages

A [4.3.0]bicyclic nucleoside that contains an unsaturated hydroxylated 3′,4′-trans linkage has been efficiently synthesised. Thus, from diacetone-d-glucose as the starting material, stereoselective Grignard reactions for the introduction of allyl groups, a nucleobase coupling and, subsequently, a ring-closing metathesis (RCM)-reaction were applied as the key reactions. The cyclohexene moiety introduced in this nucleoside reveals a large potential for further derivatisation, and as the first example, a stereoselective dihydroxylation followed by deprotection afforded a multihydroxylated bicyclic nucleoside. The configuration and conformational behaviour was determined by NMR spectroscopy and ab initio calculations, and both this bicyclic nucleoside and its unsaturated analogue were found to be strongly restricted in S-type conformations.     

Synthesis, single crystal X-ray structure and optical properties of 3,4-dimethyl-dithieno[2,3-b:3′,2′-d]thiophene-7,7-dioxide

The synthesis of the title compound (4), starting from commercial 3-bromo-4-methylthiophene, is described. The single crystal packing mode of 4, as well as the absorption and photoluminescence properties in solution and in the solid state are reported and analyzed in relation to those of the isomeric 3,5-dimethyl-dithieno[3,2-b:2′,3′-d]thiophene-4,4-dioxide (7). The different reactivities of 4 and 7 towards bromination are analyzed in the light of the results of ab initio B3LYP/6-31G^∗ calculations on both compounds.     

Novel and efficient syntheses of 3′,5′-diamino derivatives of 2′,3′,5′-trideoxycytidine and 2′,3′,5′-trideoxyadenosine. Protonation behavior of 3′,5′-diaminonucleosides

High yielding synthetic routes to 3′,5′-diamino-2′,3′,5′-trideoxycytidine and 3′,5′-diamino-2′,3′,5′-trideoxyadenosine are described. In addition, the protonation behavior of 3′,5′-diamino-2′,3′,5′-trideoxycytidine, 3′,5′-diamino-2′,3′,5′-trideoxyadenosine, 3′,5′-diamino-3′,5′-dideoxythymidine, and 3′,5′-diamino-2′,3′,5′-trideoxyuridine has been studied by means of pH-metric measurements and NMR spectroscopy. The ionization constants and the sequence of protonation sites have been determined.     

Synthesis of a series of novel 2′,3′-dideoxy-6′,6′-difluoro-3′-thionucleosides

A series of novel 2′,3′-dideoxy-6′,6′-difluoro-3′-thionucleosides 1a-d, analogues of 3TC that has high biological activities against HIV and HBV, have been synthesized from the gem-difluorohomoallyl amine 7 in a straightforward fashion. Our synthesis featured the construction of thiofuranose skeleton through ring closure of key intermediates and installation of pyrimidine ring with amino group in compounds 13a,b.     

Straightforward synthesis of 3′-deoxy-3′,4′-didehydronucleoside-5′-aldehydes via 2′,3′-O-orthoester group elimination: a simple route to 3′,4′-didehydronucleosides

Straightforward, high-yielding syntheses of 3′-deoxy-3′,4′-didehydronucleoside-5′-aldehydes and 3′-deoxy-3′,4′-didehydronucleosides starting from 2′,3′-O-orthoester derivatives of ribonucleosides are described.     

2′,3′,4′,5′-Tetraacetyl-N(3)-carboxymethylriboflavin derivatives: synthesis and fluorescence studies

The hitherto not described 2′,3′,4′,5′-tetraacetyl-N(3)-carboxymethylriboflavin (1) could be prepared starting from 2′,3′,4′,5′-tetraacetylriboflavin by alkylation with tert-butyl α-bromoacetate and benzyl α-bromoacetate, followed by deprotection reaction. The results of fluorescence studies are described.     

5′-Epimeric 3′-deoxy-3′,4′-didehydronucleoside-5′-C-phosphonates: synthesis and structural assignment by NMR and X-ray analyses

Epimeric 5′-(RS) dialkyl 3′-deoxy-3′,4′-didehydro-5′-C-phosphonates were prepared by nucleophilic addition of various dialkyl phosphites to 3′-deoxy-3′,4′-didehydronucleoside-5′-aldehydes. Whereas direct NMR configuration assignment for the C5′ atom bearing the phosphoryl and hydroxy groups using the J (P,H4′) and J (H5′,H4′) coupling constants is impossible due to the absence of the H4′ atom, successful separation, crystallisation and X-ray crystallographic analysis of a pair of epimeric 5′-C-phosphonates, followed by correlation with a series of NMR parameters, led to efficacious configuration assignment of individual epimers in the mixtures.     

Application and details of photoinduced oxidative cyclization of 5-(4′,9′-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones and related compounds

As novel methodology for synthesizing the furan ring, a photoinduced oxidative cyclization of 5-(4′,9′-methanocycloundeca-2′,4′,6′,8′,10′-pentaenylidene)pyrimidine-2,4,6(1,3,5H)-triones (7a-c) and related compounds 9a-c was accomplished to give 5,10-methanocycloundeca[4,5]furo[2,3-d]pyrimidine-2,4(1,3H)-dionylium tetrafluoroborates (8a-c⁺·BF₄⁻) and related compounds 2a-c⁺·BF₄⁻, respectively. In the photoinduced oxidative cyclization, the molecular oxygen in air is used as oxidant and the reaction proceeds under mild conditions to give desired products without byproducts, and thus, it is interesting from the viewpoint of the green chemistry. On the reactions of the mono-substituted derivatives 7d,e and 9e,f, the selectivity of the photoinduced cyclizations were reversed as compared with those of the DDQ-promoted oxidative cyclizations. By the NMR monitoring of the reactions of 7a and deuterated compound 7a-D₂ under degassed conditions, the details of the reaction pathway were clarified and rationalized on the basis of the MO calculation by the 6-31G^∗ basis set of the MP2 levels as well.     

Synthesis and structural investigation of 1′,3′,3′-trimethyl-6-hydroxy-spiro(2H-1-benzopyran-2,2′-indoline), 1′,3′,3′-trimethyl-6-methacryloyloxy-spiro(2H-1-benzopyran-2,2′-indoline) and a copolymer with methyl methacrylate by 1D and 2D NMR spectroscopy

Photo-responsive spiropyran-based compounds, such as, 1′,3′,3′-trimethyl-6-hydroxy-spiro(2H-1-benzopyran-2,2′-indoline) [OHSP], its monomer, such as 1′,3′,3′-trimethyl-6-methacryloyloxy-spiro(2H-1-benzopyran-2,2′-indoline) [MOSP] and its copolymers with methyl methacrylate [MMA] were synthesised using conventional synthetic routes. The copolymerisation was carried out either in tetrahydrofuran [THF] or in toluene using 2,2′-azobisisobutyronitrile [AIBN] as an initiator. The structures of these materials were investigated using ¹H and ¹³C NMR spectroscopy. DEPT-135, HCCOSW and COSY45 NMR experiments were used to assign and interpret the complex structure of spiropyran based materials.     

Enantiospecific synthesis of 5′,5′,5′-trifluoro-5′-deoxyneplanocin A

(−)-(1S,4R)-4-Hydroxy-2-cyclopenten-1-yl acetate provided a convenient entry point for a 12-step chiral preparation of 5′,5′,5′-trifluoro-5′-deoxyneplanocin A.     

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.     

3′-Selective modification of a 4′,5′-didehydro-5′-deoxy-2′,3′-epoxyuridine using nucleophiles

1-(2,3-Anhydro-5-deoxy-4,5-didehydro-α-l-erythro-pent-4-enofuranosyl)uracil 4 was obtained by the treatment of 5′-iodo-2′,3′-epoxyuridine 5 with LiHMDS in excellent yield. The pyrimidine nucleoside 4 possesses quite unique vinyl epoxide moiety within the molecules. The reactions of 4 with a variety of nucleophiles gave 3′-substituted pyrimidine nucleosides without the formation of the corresponding 2′-substituted isomers. In the case of NaN₃ or PhSH, the corresponding 5′-adduct was obtained as a minor product together with the expected 3′-adduct.     

New N-acyl, N-alkyl, and N-bridged derivatives of rac-6,6′,7,7′-tetramethoxy-1,1′,2,2′,3,3′,4,4′-octahydro-1,1′-bisisoquinoline

The preparation of potential new ligand systems based on the rac-1,1′,2,2′,3,3′,4,4′-octahydro-6,6′,7,7′-tetramethoxy-1,1′-bisisoquinoline skeleton has been investigated. Syntheses of N-(2-bromobenzyl), N-(3-acetoxybenzyl), N-acetyl, N-chloroacetyl, N-chlorocarbonyl, N-ethoxycarbonyl and N-tert-butyloxycarbonyl derivatives and five macrocyclic, polyether containing derivatives are described.     

Synthesis and anti-HIV activities of phosphate triester derivatives of 3′-fluoro-2′,3′-dideoxythymidine and 3′-azido-2′,3′-dideoxythymidine

Fatty acyl-glycol phosphate triester conjugates of 3′-fluoro-2′,3′-dideoxythymidine (FLT) were prepared in three steps from the reaction of diisopropylphoramidous dichloride with fatty acyl-substituted glycols, followed by a coupling reaction with FLT and oxidation with tert-butyl hydroperoxide (t-BuOOH). Additionally, a number of fatty alcohols were reacted with diisopropylphoramidous dichloride to produce the phosphitylating intermediates, which underwent coupling reactions with 3′-azido-2′,3′-dideoxythymidine (AZT) and FLT followed by oxidation with t-BuOOH to yield fatty alcohol phosphate triester derivatives of AZT and FLT.     

Diastereoselective synthesis of 1-alkyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3′-(1′,2′,3′,4′-tetrahydroquinolines)

Knoevenagel products formed by the condensation of N-monoalkyl barbituric acids with o-tert-amino benzaldehydes undergo tert-amino effect reactions (T-reactions) yielding 1-alkyl-2,4,6-trioxoperhydropyrimidine-5-spiro-3′-(1′,2′,3′,4′-tetrahydroquinoline) derivatives as a mixture of (S^∗,S^∗)- and (S^∗,R^∗)-diastereomers. Mostly, the major diastereomer has the S^∗,S^∗-configuration. According to X-ray diffraction data in the solid form and NOE data in solution, diastereoselectivity of the T-reactions can be associated with the structure of the Knoevenagel products whose conformation is fixed by the strong intramolecular C-H?π interaction.     

Highly efficient synthesis of 2′,3′-didehydro-2′,3′-dideoxy-β-nucleosides through a sulfur-mediated reductive 2′,3′-trans-elimination. From iodomethylcyclopropanes to thiirane analogs

Taking into account the thiophilic properties of iodine, a very simple methodology to achieve 2′,3′-didehydro-2′,3′-dideoxy-β-nucleosides in high yield was performed, using mild, and inexpensive conditions, by means of the treatment of 2′-deoxy-3′,5′-dibenzoyl-2′-iodo-β-nucleoside derivatives with NaHS. The process has shown to be highly dependent of the relative geometry between the iodine atom and the adjacent leaving group. In this way, different essays carried out with pyranose derivatives have concluded in no reaction when the vicinal groups to eliminate do not adopt a trans-diaxial disposition. In addition, the treatment of 2-iodomethyl-cyclopropane-1,1-dicarboxylic acid diethyl ester under the same conditions softly and readily leads to the obtention of a mixture of the expected 2-allyl-malonic acid diethyl ester (as the minor product) and the thiirane derivative 2-thiiranylmethyl-malonic acid diethyl ester (as the major product). In this case, the responsible of the reaction progress are the nucleophilic properties of the sulfur atom rather than the thiophilic character of the iodine atom.     

Novel chiral C1-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinolines: synthesis, resolution, and applications in catalytic enantioselective reactions

A straightforward synthesis of a structurally constrained C₁-1′,2′,3′,4′-tetrahydro-1,1′-bisisoquinoline 1 is described. Resolution of this compound has been achieved successfully. The preparation of chiral N-alkyl, urea, and thiourea derivatives as potential new chiral ligands, based on the parent compound 1, is reported. Chiral compound 1 induced very good selectivity and yield in the addition of either Et₂Zn (85% ee, 96% yield) or nitromethane (85% ee, 60% yield) to benzaldehyde.     

Facile acid-catalyzed condensation of 2-hydroxy-2,2′-biindan-1,1′,3,3′-tetrone with phenols, methoxyaromatic systems and enols

Various phenols, methoxy aromatic compounds, 3- and 4-hydroxycoumarins and enols smoothly condense with 2-hydroxy-2,2′-biindan-1,1′,3,3′-tetrone 1 in an acid medium producing 2-aryl/alkyl-2,2′-biindan-1,1′,3,3′-tetrones in high yields. The adducts of resorcinol, 1,3,5-trihydroxybenzene and α- and β-naphthols of 1 preferably remain in the intramolecular hemi-ketal form, confirmed by X-ray diffraction studies. On the other hand para and meta substituted phenols condense with 1 in an acid medium to produce 6 or 7 substituted 2′,4-spiro(1′,3′-indanedion)-indeno[3,2-b]chromenes in good yields.     

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.