Allyl protection of internucleotide linkage

Allyl group serves as a useful protecting group for an internucleotide bond, which can be removed mildly by brief treatment with a catalytic amount of Pd[P(C₆H₅)₃]₄ and various nucleophiles.     

Synthesis of an organosilicon hyperbranched oligomer containing alkenyl and silyl hydride groups

A new organosilicon hyperbranched oligomer has been prepared that contains both double bonds and silyl hydride groups. The monomer is prepared via the hydrosilylation of propargyl chloride with methyldichlorosilane in the presence of a platinum catalyst. The product is a mixture resulting from both α- and β-addition. Treatment of the monomer mixture with magnesium results in the formation of a hyperbranched oligomer, which is then treated with LiAlH₄. Control of monomer addition speed to the magnesium is critical in order to keep head-head coupling low. The resulting oligomer is air- and water-stable, and has an average degree of polymerization of 8. This material gives a char yield of 24% but after crosslinking with platinum catalyst, the char yield increases to 69%. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3778–3784, 1999     

Synthesis,characterization of an AlPO-CJ2 analogue containing heteroatomic Eu

An analogue of AlPO-CJ2 microporous aluminophosphate containing heteroatomic Eu was hydrothermally synthesized in situ in the reactant system of carbamide-NH4-F-Al2O3-P2O5-H2O, and characterization by ICP, powder XRD, M?ssbauer spectra, 31P MAS NMR and luminescent spectroscopy prove that Eu is incorporated into the framework.     

Synthesis of an amino acid based phosphodiester linkage containing cryptand.

The synthesis of an amino acid based phosphodiester linkage containing cryptand is described. The macrocyclic ring is constructed using Boc-L-Ser(OBn)-OH, Boc-D-Ser(OBn)-OH, diethylene glycol and ethylene dioxydiacetic acid. The phosphodiester linkage was introduced employing 4-chlorobenzyl dichlorophosphite leading to the cryptand.     

Synthesis,separation, and stereochemistry of diastereomeric oligodeoxyribonucleotides having a 5′-terminal internucleotide phosphorothioate linkage

An automated, solid-phase, phosphoramidite-coupling method provided the title compounds, up to a hexadecamer, for HPLC isolation of diastereomerically pure samples, and comparative digestions with snake venom phosphodiesterase and nuclease P1.     

Solid-Phase Synthesis of Oligodeoxynucleotides containing phosphoramidate internucleotide linkages and their specific chemical cleavage

Oligonuclecotides bearing phosphoramidate internucleotide linkages can be prepared chemically by standard solid-phase DNA synthesis. Thus, phosphoramidate internucleotide bonds can be placed at will into specific positions within a given DNA fragment. The backbone-modified DNA fragments prepared in this way are susceptible to a specific chemical cleavage.     

Chemical synthesis, crystal structure and enzymatic evaluation of a dinucleotide spore photoproduct analogue containing a formacetal linker

Spore photoproduct (SP) is the exclusive DNA photodamage product found in bacterial endospores. Its photoformation and repair by a metalloenzyme spore photoproduct lyase (SPL) composes the unique SP biochemistry. Despite the fact that the SP was discovered almost 50 years ago, its crystal structure is still unknown and the lack of structural information greatly hinders the study of SP biochemistry. Employing a formacetal linker and organic synthesis, we successfully prepared a dinucleotide SP isostere 5R-CH(2) SP, which contains a neutral CH(2) moiety between the two thymine residues instead of a phosphate. The neutral linker dramatically facilitates the crystallization process, allowing us to obtain the crystal structure for this intriguing thymine dimer half a century after its discovery. Further ROESY spectroscopic, DFT computational, and enzymatic studies of this 5R-CH(2) SP compound prove that it possesses similar properties with the 5R-SP species, suggesting that the revealed structure truly reflects that of SP generated in Nature.     

A convenient method for the formation of internucleotide linkage

Internucleotide linkage can be made readily by reaction of $\text{N}$-unprotected nueleosides and phosphorochloridates or $\text{p}$-nitrophenyl phosphates by the assistance of Grignard reagents.     

Synthesis and characterization of new cross-linked terpolymer systems containing silyl group

A series of acrylic terpolymers containing silyl pendant groups was prepared by free radical cross-linking copolymerization. Me₃Si, Et₃Si and t-BuMe₂Si together with cubane-1, 4-dicarboxylic acid (CDA) were covalently linked with 2-hydroxyethyl methacrylate (HEMA). The silyl-linked HEMA are abbreviated as TMSiEMA, TESiEMA and TBSiEMA respectively. Cubane-1, 4-dicarboxylic acid (CDA) linked to two HEMA group is the cross-linking agent (CA). Free radical cross-linking terpolymerization of the methyl methacrylate (MMA) and methacrylic acid (MAA) with two different molar ratios of organosilyl monomers and CA was carried out at 60–70 ^∘C. The compositions of the cross-linked three-dimensional polymers were determined by FT-IR spectroscopy. The glass transition temperature (Tg) of the network polymers was determined calorimetrically. The Tg of network terpolymers increases with increasing of cross-linking degree. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). The gels swelled more in SIF than in SGF. The swelling behaviour of the copolymers was dependent on the content of MAA groups and caused a decrease in gel swelling in pH 1 or an increase in gel swelling in pH 7.4. Based on the great difference in swelling ratio at pH 1 and 7.4 for P-1, P-6 and P-10 appear to be good candidates for colon-specific drug delivery.     

Synthesis of an NDPK phosphocarrier domain peptide containing a novel triazolylalanine analogue of phosphohistidine using click chemistry

Click phosphorylation of a propargylated unprotected peptide and phosphoryl azide using chaotrope-assisted Cu(I)-catalyzed 1,3-dipolar cycloaddition enabled a high-yielding and rapid synthesis of a nucleoside diphosphate kinase (NDPK) phosphocarrier domain. The synthesis showcases a valuable synthetic platform for the synthesis of biologically relevant phosphopeptide analogues.     

Synthesis of the first double-functionalized dinucleotide mRNA cap analogue for its specific labeling

The modification of various important nucleotide-based molecules (such as nucleotides, RNA, DNA, oligonucleotides) with fluorophores, affinity tags and reactive moieties is of enormous utility for studying their localization, structure and dynamics, as well as diverse biological functions involving their interacting partners. Herein, we report chemical methodology in which the dinucleotide mRNA cap analogue is doubly modified within its second nucleotide. The prepared dinucleotide contains an alkyne at the N2-position of guanine, and levulinic acid within the ribose moiety. Such modifications may be further used for specific labeling of the cap, for instance with a fluorophore that will allow the molecule to be tracked inside the cell and an attachment cell-penetrating peptide that will help to deliver it to the area of interest. Exemplar molecules were attached in order to demonstrate the utility of the newly synthesized cap analogue.     

Synthesis of the Lewis a trisaccharide based on an anomeric silyl fluorous tag

The synthesis of the trisaccharide Lewis a was performed using an anomeric fluorous silyl protective group. This methodology allowed us to fully characterize each product (NMR, MS) and monitor each synthetic step (TLC). Although the product purifications could be performed by fluorous-solid-phase extraction (F-SPE) technology, standard chromatography could be used to effect purification if necessary. Trichloroethoxy carbonyl (Troc) protection of the amino group of the glucosamine moiety was found essential to allow protecting group manipulation of the fluorous protected sugar.     

A photoactive isoprenoid diphosphate analogue containing a stable phosphonate linkage: synthesis and biochemical studies with prenyltransferases

A number of biochemical processes rely on isoprenoids, including the post-translational modification of signaling proteins and the biosynthesis of a wide array of compounds. Photoactivatable analogues have been developed to study isoprenoid utilizing enzymes such as the isoprenoid synthases and prenyltransferases. While these initial analogues proved to be excellent structural analogues with good cross-linking capability, they lack the stability needed when the goals include isolation of cross-linked species, tryptic digestion, and subsequent peptide sequencing. Here, the synthesis of a benzophenone-based farnesyl diphosphate analogue containing a stable phosphonophosphate group is described. Inhibition kinetics, photolabeling experiments, as well as X-ray crystallographic analysis with a protein prenyltransferase are described, verifying this compound as a good isoprenoid mimetic. In addition, the utility of this new analogue was explored by using it to photoaffinity label crude protein extracts obtained from Hevea brasiliensis latex. Those experiments suggest that a small protein, rubber elongation factor, interacts directly with farnesyl diphosphate during rubber biosynthesis. These results indicate that this benzophenone-based isoprenoid analogue will be useful for identifying enzymes that utilize farnesyl diphosphate as a substrate.     

Synthesis and characterization of aromatic polymers containing pendant silyl groups. I. Polyarylates

Polyarylates containing pendant silyl group were prepared by the phase-transfer catalyzed, two-phase polycondensations of 2,2-bis (4-hydroxyphenyl) propane with corresponding dicarbonyl chlorides such as 2-trimethylsilylterephthaloyl chloride, 5-trimethylsilylisophthaloyl chloride, 5-dimethylphenylsilylisophthaloyl chloride, and 5-triphenylsilylisophthaloyl chloride. The resulting amorphous polyarylates with glass transition temperatures of 163–214°C had inherent viscosities in the range of 0.41–0.95 dL/g. These polyarylates were readily soluble in common chlorinated hydrocarbons and it was possible to obtain transparent, flexible, and tough films from the polymer solutions. The prepared polyarylates showed fairly good thermal stabilities as well as tensile strengths, i.e., the tensile strengths of the cast films from chloroform solution were 6.0–6.7 kg/mm². And TGA data revealed 10% weight losses and residual weights at 800°C were 437–495°C and 27–40% under nitrogen atmosphere, respectively. © 1992 John Wiley & Sons, Inc.     

Synthesis of an iminosugar based peptidomimetic analogue

The synthesis of an 1-deoxymannojirimycin based analogue of a known HIV-protease inhibitor is described. The strategies employed for introduction of the pharmacophore groups onto the azasugar scaffold were based on regioselective reactions of the hydroxyl groups of the natural product and of d-fructopyranoside derivatives.     

Synthesis and properties of polyurethanes and polyureas containing 2,5-thiophenylene linkage

A novel diisocyanate monomer, thiophene-2,5-diisocyanate (ThDI) was prepared from readily available adipic acid via the intermediate formation of thiophene-2,5-dicarboxylic acid chloride (ThDAC) and thiophene-2,5-dicarboxylic acid azide (ThDAA) which was subjected to a Curtius rearrangement. Polyurethanes and polyureas containing 2,5-thiophenylene linkage were synthesized by the polycondensation of thiophene-2,5-diisocyanate with various diols and diamines, respectively, in N,N-dimethylformamide. Polymerization conditions were optimized and the high yields of polymers were obtained. The identity of ThDI, model compounds, and the resulting polymers was confirmed by elemental analysis and spectroscopic methods. These polyurethanes and polyureas were found to have inherent viscosities in the range of 0.33–0.68 dL/g. Some physical properties of these polymers were also investigated.