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Summary.  An 5-ethyl-2-thiouracil derivative with a 6-(tetrahydronaphthalen-1-yl)methyl substituent was synthesized by condensation of thiourea with an adequate β-ketoester which in turn was synthesized in a single step from (tetrahydronaphthalen-1-yl)acetonitrile. The latter starting material was also used to synthesize an analogously substituted tetrahydronaphthalen-1-yl substituted uracil with a locked conformation. Only the non-nucleoside derivatives prepared from the desulfurized substituted 2-thiouracil showed moderate activity against HIV whereas a corresponding non-nucleoside derivative was devoid of activity against HIV. [ABSTRACT FROM AUTHOR]

Nucleic acids play a pivotal role in life processes. The endeavours to shed light on the essential properties of these intriguing building blocks led us to the synthesis of different analogues and the investigation of their properties. First various peptide nucleic acid monomers and oligomers have been synthesized, using an Fmoc/acyl protecting group strategy, and their properties studied. The serendipitous discovery of a side reaction of coupling agents led us to the elaboration of a peptide sequencing method. The capricious behaviour of guanine derivatives spurred the determination of their substitution pattern using 13C, 15N NMR, and mass spectrometric methods. The properties of guanines initiated the logical transition to the study of supramolecular systems composed of purine analogues. Thus, xanthine and uracil derivatives have been obtained and their supramolecular self‐assembly properties scrutinized in gas, solid, and liquid states and at solid‐liquid interfaces. [ABSTRACT FROM AUTHOR]

Two new intercalated nucleic acid monomers, X and Y, possessing enone as linker have been synthesized. The monomers were incorporated into 14‐mer polypyrimidine strand to act as triplex‐forming oligonucleotide (TFO). The thermal stabilities of the formed parallel triplexes, parallel and antiparallel duplexes were evaluated to show high stability of its parallel triplexes at pH 5.0 and pH 7.2, while limited stability at pH 6.0 compared to unmodified triplex. The architectures of enone linker are shown to disturb the planarity of its parallel and antiparallel duplexes and consequently the π‐π stacking ability with the neighboring nucleobases. The data was confirmed by molecular dynamics simulation and binding energy calculations. Characteristic fluorescence spectra were also investigated to show the ability of X and Y containing TFO to discriminate parallel triplex from parallel and antiparallel duplex. [ABSTRACT FROM AUTHOR]

An expedient and pseudo four-component reaction catalyzed by nano-Al2O3/BF3/Fe3O4 in water at room temperature to synthesize of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines has been described. The catalyst was removed from the mixture of reaction by an external magnet and was reusable for several times without any considerable loss of its activity. The obtained 1,3-oxazine compounds were characterized by various methods such as FT-IR, 1H NMR and melting point. Environmentally benign, easy work-up, excellent yields, clean and convenient procedure are some advantages of this method. [ABSTRACT FROM AUTHOR]

Indole was conjugated to deoxyuridine either directly or via ethynyl linkage to synthesize two new DNA monomers. Due to the high reactivity of indole toward electrophilic substitution reactions, unwanted iodination was observed during the oxidation step with iodine oxidizer in automated DNA synthesizer leading to an additional oligonucleotide having extra 126 mass unit beside the desired oligonucleotide. On the other hand, using CSO oxidizer ensured the formation of the wanted oligonucleotide. Oligonucleotide synthesis was confirmed by MALDI‐TOF‐MS analysis. Polypyrimidine strands containing non‐iodinated indole nucleoside were able to form parallel triplexes, antiparallel RNA and DNA duplexes. The thermal denaturation experiments showed higher triplex stabilization for 5‐(5‐indolylethynyl)‐2′‐deoxyuridine over 5‐(5‐indolyl)‐2′‐deoxyuridine as the triple bond allows twisting to put the indole into a proper position within the triplex encouraging better π‐π stacking. [ABSTRACT FROM AUTHOR]

A new intercalating nucleic acid monomer Z comprising an 3‐(9‐((4‐oxyphenyl)ethynyl)‐6H‐indolo[2,3‐b]quinoxalin‐6‐yl)propan‐1‐amine moiety was synthesized. When Z was inserted into triplex forming oligonucleotides, high thermal stability was observed for its corresponding Hoogsteen‐type triplexes. Three‐way junction (TWJ) was studied by targeting a DNA strand to the foot of a DNA or an RNA hairpin. When Z was inserted into the DNA strand, this resulted in the highest increase of thermal melting ever reported for a TWJ modified by insertion of an intercalator into the junction site. Experiments with mismatches confirmed formation of the TWJ. Improvements in stability of a G‐quadruplex were achieved by insertion of the monomer Z by replacement of one of the nucleotides in the TGT loop. The first steps in the synthesis of the monomer Z were condensation of 5‐iodoisatin with o‐phenylene diamine under reflux in acetic acid and subsequent alkylation reaction with 2‐(3‐bromopropyl)isoindoline‐1,3‐dione followed by suitable reduction led to 3‐(9‐Iodo‐6H‐indolo[2,3‐b]quinoxalin‐6‐yl)propan‐1‐amine which in turn was treated with ethyl trifluoroacetate with formation of 2,2,2‐trifluoro‐N‐(3‐(9‐iodo‐6H‐indolo[2,3‐b]quinoxalin‐6‐yl)propyl)acetamide. This compound was reacted by Sonogashira coupling conditions to give the diol which was converted into the DMT‐protected phosphoramidite, which in turn was used to incorporate the monomer Z into oligonucleotides. [ABSTRACT FROM AUTHOR]

Twisted intercalating nucleic acid (TINA) has the ability to stabilize Hoogsteen triplex formation. New oligonucleotides containing 3-(pyren-1-ylethynyl)indole as a DNA linked intercalator backbone have been added to the TINA family and their synthetic route has been devised. The indole ring, under acidic conditions, polarizes the triple bond in the intercalator and this makes hydration of the triple bond possible during the DNA synthesis and an oligonucleotide with 1-(indol-3-yl)-2-(pyren-1-yl)ethanone as the intercalator is formed. Insertion of the unhydrated and hydrated linker systems gave characteristic UV spectra comparable to its monomeric diols due to π-conjugated and isolated pyrene systems, respectively. Thermal denaturation profile at pH 6-7.2 showed excellent stabilization of the triplex upon insertion of 3-(pyren-1-ylethynyl)indole when compared to wild-type triplexes. The investigation includes fluorescence spectroscopic and molecular modeling studies. [ABSTRACT FROM AUTHOR]

1,4-Dihydroxyanthraquinone and 1,8-dihydroxyanthraquinone were alkylated with 3-bromopropan-1-ol and subsequently transformed into the corresponding DMT protected phosphoramidite building blocks for insertion into loops of the G-quadruplex of the thrombin binding aptamer (TBA). The 1,4-disubstituted anthraquinone linker led to a significant stabilization of the G-quadruplex structure upon replacing a T in each of two neighboring lateral TT loops and a 26.2° increase in thermal melting temperature was found. CD Spectra of the modified quadruplexes confirmed anti-parallel conformations in all cases under potassium buffer conditions as previously observed for TBA. Although the majority of the anthraquinone modified TBA analogues showed a decrease in clotting times in a fibrinogen clotting assay when compared to TBA, modified aptamers containing a 1,8-disubstituted anthraquinone linker replacing G8 or T9 in the TGT loop showed improved anticoagulant activities. Molecular modeling studies explained the increased thermal melting temperatures of anthraquinone-modified G-quadruplexes. [ABSTRACT FROM AUTHOR]

A series of new 5-allyl-6-benzylpyrimidin-4(3H)-ones bearing different substituents at the C-2 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against human immunodeficiency virus type 1 (HIV-1) in the human T-lymphotropic type (MT-4 cell cultures). The majority of the title compounds showed moderate to good activities against HIV-1. Amongst them, 5-allyl-6-benzyl-2-(3- hydroxypropylthio)pyrimidin-4(3H)-one analogue 11c exhibited the most potent anti-HIV-1 activity (IC50 0.32 µM). The biological testing results clearly indicated that the substitution at C-2 position of the pyrimidine ring could increase the anti-HIV-1 reverse transcriptase (RT) activity. [ABSTRACT FROM AUTHOR]

An allopurinol locked nucleic acid (LNA) monomer was prepared by a novel strategy through C6 deamination of the corresponding 8-aza-7-bromo-7-deazaadenine LNA monomer with aqueous sodium hydroxide. An 8-aza-7-deazaadenine LNA monomer was also synthesized by a modification of the new synthetic pathway. N-Glycosylation at the 8-position was prevented by steric hindrance from the 7-bromo atom in the starting material 8-aza-7- bromo-7-deazaadenine. In the final step of the synthesis, the bromine was removed together with a benzyl protecting group by catalytic reduction with ammonium formate to give the required LNA monomers. [ABSTRACT FROM AUTHOR]

Three or four aromatic rings interconnected by acetylene bridges form a stiff conjugated system with sufficient conformational freedom to make it useful to link together the two strands of a DNA clamp. Upon targeting a ssDNA, the conformational flexibility allows better stacking of the linker to the underlying non-planar base triplet in the formed triplex. This type of triplexes has a substantially higher thermal melting temperature which can be further improved by inserting locked nucleic acids (LNAs) in the Hoogsteen part of the clamp. An extremely high sensitivity to mismatches is observed in an octamer triplex when placed in the middle of the sequence. [ABSTRACT FROM AUTHOR]

A new intercalating nucleic acid monomer Y was obtained via alkylation of pyren-1-ol with ( S)-(+)-2-(2,2-dimethyl-1,3-dioxolan-4-yl)ethanol under Mitsunobu conditions followed by hydrolysis with 80% aqueous acetic acid to give a diol which was tritylated with 4,4′-dimethoxytrityl chloride followed by treatment with 2-cyanoethyltetraisopropylphosphordiamidite in the presence of N, N′-diisopropylammonium tetrazolide. In this way the monomer Y was obtained as its dimethoxytrityl-protected phosphoramidite building block for standard DNA synthesis. The corresponding oligonucleotides from Y have nearly identical hybridization properties with those of intercalating nucleic acid (INA) where neighboring oxygen and carbon atoms are interchanged in the linker. The synthesis of monomer Y avoids the use of allergic intermediates which are a problem in the synthesis of INA. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The first investigation of Linum grandiflorum resulted in the isolation of one new acylated flavone O-diglycoside known as luteolin 7-O-α-D-(6'''-E-feruloyl)glucopyranosyl (1 → 2)-β-D-glucopyranoside, and one new cyanogenic glycoside known as 2-[(3'-isopropoxy-O-β-D-glucopyranosyl)oxy]-2-methylbutanenitrile, together with four known flavonoid glycosides, three known cyanogenic glycosides and one alkyl glycoside. The new compounds were structurally elucidated via the extensive 1D, 2D NMR and DIFNOE together with ESI-TOF-CID-MS/MS and HR-MALDI/MS. [ABSTRACT FROM AUTHOR]

Abstract  A series of substituted thieno[2,3-d]pyrimidines was synthesized starting from ethyl-2-amino-4-isopropylthiophene-3-carboxlate. Reaction of 2-hydrazino-5-isopropyl-thieno[2,3-d]pyrimidin-4(3H)-one and its 3-methyl analogue with different reagents afforded thieno[2,3-d]triazolo[4,3-a]pyrimidines and thieno[3,2-e]triazolo[4,3-a]pyrimidines, beside open chain derivatives. [ABSTRACT FROM AUTHOR]