Cyanoethyl Derivatives Research Articles

Synthesis and properties of tetrazole-containing polyelectrolytes based on chitosan, starch, and arabinogalactan

Abstract The synthesis of tetrazole-containing derivatives of chitosan, starch, and arabinogalactan was carried out by a sequence of reactions including cyanoethylation of polysaccharides and subsequent azidation of cyanoethyl derivatives. The reaction of cyanoethylation of polysaccharides with acrylonitrile proceeds in the temperature range 40–60°C in the presence of NaOH. The transformation of nitrile groups into tetrazole rings (azidation) of cyanoethylated polysaccharide derivatives was carried out with a mixture of sodium azide with ammonium chloride in DMF at 105°C. The reaction with the participation of derivatives of starch and arabinogalactan is characterized by the degree of conversion of nitrile groups into tetrazole rings, which is close to the maximum. The introduction of unsubstituted tetrazole rings into the structure of polysaccharides of acidic N–H substantially changes some of their properties. Like other carbo- and hetero-chain polymers containing N–H unsubstituted tetrazole rings in the structure, tetrazolated polysaccharides exhibit the properties of acidic polyelectrolytes. Tetrazole-containing derivatives of chitosan exhibit the properties of polyampholytes. The presence of tetrazole rings in the structure of modified polysaccharides allows the reaction with epoxy compounds to yield network polymers capable of limited swelling in aqueous media with the formation of polyelectrolyte hydrogels.

Synthesis, characterization and antibacterial activities of nickel(II) and copper(II) complexes of an N-pendent cyanoethyl derivative of a tetraazamacrocycle

An octamethyl substituted tetraazacylotetradecadiene ligand salt Me8[14]diene.2HClO4 (L.2HClO4) on reduction produced three isomeric C-chiral ligands LA, LB & LC. Interaction of LB with excess acrylonitrile resulted in a N-pendent cyanoethyl derivative ligand, LBX. Reaction of LBX with nickel(II) salt, Ni(CH3COO)2.4H2O followed by the addition of NaClO4 afforded the complex, [NiLB](ClO4)2, as resulted by the interaction with LB instead of LBX with the same nickel(II) salt which on twelve hours reflux with acrylonitrile yielded square planar nickel(II) diperchlorate complex, [NiLBX](ClO4)2, This complex underwent axial addition reactions with KX (X = SCN, Br or I) and NaNO2 to form octahedral diisothiocyanatonickel(II) complex, [NiLBX(NCS)2]; dibromidonickel(II) complex, [NiLBXBr2]; diiodidonickel(II) complex, [NiLBXI2] and monoaquamononitronickel(II) perchlorate complex, [NiLBX(NO2)(H2O)](ClO4) respectively. The ligand, LBX with copper(II) chloride yielded purple dichloridocopper(II) complex, [CuLBXCl2] of octahedral geometry which underwent axial substitution reactions with KX and NaNO2 to form octahedral diisothiocyanatocopper(II) complex [CuLBX(NCS)2]; dibromidocopper(II) complex [CuLBXBr2]; diiodidocopper(II) complex, [CuLBXI2] and dinitrocopper(II) complex [CuLBX(NO2)2] respectively. These complexes were characterized on the basis of elemental, spectroscopic, magnetochemical and conductrometric analysis. The antibacterial activities of the ligand and complexes have been investigated against different human pathogenic gram positive and gram negative bacteria.

Synthesis and Biological Activity of Cyanoethyl Derivatives of Fusidic Acid

3,11-Dihydroxy and 3,11-dioxo triterpenoids of the fusidane series reacted with acrylonitrile in 1,4-dioxane in the presence of alkali and phase-transfer catalyst to give mono- and bis(2-cyanoethoxy) and 2-cyanoethyl derivatives. The reaction with 3,11-dioxo analog afforded 2,2-disubstituted derivative as a result of addition of two cyanoethyl groups to the α-position with respect to the C3=O carbonyl group. The isolated compounds were screened for antibacterial and antifungal activities.

Synthesis and Biological Activity of Nitrilic Derivatives of the Methyl Ester of Maleopimaric Acid

An effective method of a modification of the anhydride ring of the maleopimaric acid methyl ester by means of the cyanoethylation reaction was developed. A primary screening of a cytotoxic activity in vitro demonstrated an ability of the cyanoethyl derivative of the maleopimaric acid methyl ester to induce the death of the PC-3 cells of prostate cancer.

Synthesis of new cyanoethyl derivatives from 3-oxotriterpenoids

Reaction of 3-oxotriterpenoids and steroids with acrylonitrile in the presence of BnEt3NCl and 30% KOH in dioxane proceeds with the formation of 2,2-biscyanoethyl derivatives substituted in the α-position to 3-oxo group. In the presence of several α-hydrogen atoms at the 3-oxo group the reaction of cyanoethylation involved the positions C 4 and C 5 , leading to 2,2,5-tricyanoethyl and 2,4-dicyanoethyl derivatives. The cyanoethylation of tetracyclic compounds occurred with the formation of monocyanoethyl derivatives with an overall increase in the yield.

Synthesis and cytotoxic activity of usnic acid cyanoethyl derivatives

Cyanoethyl derivatives of usnic acid (natural lichen metabolite) were prepared. The reaction proceeded as a C-alkylation process via addition of two acrylonitrile molecules. Cytotoxic effect of the synthesized derivatives on the blood tumor cell lines was studied.

Synthesis of novel polybrominated benzimidazole derivatives—potential CK2 inhibitors with anticancer and proapoptotic activity

The efficient method for the synthesis of novel cell permeable inhibitors of protein kinase CK2 with anticancer and proapoptotic activity has been developed. A series of polybrominated benzimiadazole derivatives substituted by various cyanoalkyl groups have been synthesized. Cyanoethyl derivatives were obtained by Michael type addition of 4,5,6,7-tetrabromo-1H-benzimidazole (TBBi) and 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole to acrylonitrile, whilst cyanomethyl, cyanopropyl and cyanobutyl analogs by N-alkylation of 4,5,6,7-tetrabromo-1H-benzimidazole and 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole with appropriate cyanoalkyl halides. The inhibitory activity against protein kinase rhCK2α catalytic subunit and cytotoxicity against two human cancer cell lines: acute lymphocytic leukemia (CCRF-CEM) and breast (MCF-7) were evaluated for all newly synthesized compounds. Additionally, the proapoptotic activity toward leukemia cells and intracellular inhibition of CK2 for the most cytotoxic derivatives have been performed, demonstrating 4,5,6,7-tetrabromo-2-methyl-1H-benzimidazole as a new selective inhibitor of rhCK2 with twenty-fold better proapoptotic activity than parental compound (TBBi).

Properties of new polyelectrolytes based on cellulose and poly(vinyl alcohol)

Carbo- and heterochain tetrazole-containing polyelectrolytes are synthesized via a sequence of cyanoethylation reactions followed by azidation of cyanoethyl derivatives of cellulose and poly(vinyl alcohol). The products exhibit properties typical for polymers containing N-H unsubstituted tetrazole cycles.

Synthetic transformations of higher terpenoids: XXIV. Synthesis of cyanoethyl derivatives of lupane triterpenoids and their transformation into 1,2,4-oxadiazoles

Cyanoethylation of lupane triterpenoids was performed. Amide oximes of 3β-O-(2-cyanoethyl)-betulinic acid methyl ester and 3β-O-acetyl-28-O-(2-cyanoethyl)betulin and the corresponding O-[2-(1,2,4-oxadiazol-3-yl)ethyl] lupane derivatives were obtained.

Nanoscale aryleneethynylene oligomers incorporating fluorenone units as electron-dopable molecular wires

The first general synthetic procedures to obtain fluorenone-containing aryleneethynylene oligomers have been developed. The strategy involves stepwise Sonogashira cross-coupling methodology, with 2,7-diethynylfluorenone and 1,4-diiodo-2,6-di(hexyloxy)benzene building blocks, with terminal benzenethiol functionality protected as cyanoethyl derivatives. A second family of compounds contains a central 9-[(4-pyridyl) methylene]fluorene or 9-[di(4-pyridyl)methylene]fluorene unit in the backbone. UV-Vis absorption studies in solution establish that the increase of molecular lengths ca. 4 nm (compounds 15 and 16) to ca. 7 nm (compounds 17, 27 and 28) results in a very small red shift, with the effective conjugation length slightly longer than that 1,4-di(phenylethynyl)benzene (PEPEP) subunits. The pyridyl groups in 27 and 28 are weakly conjugated to the pi-electron backbone (UV-Vis data) which is consistent with twisted conformation observed in the X-ray crystal structures of model compounds and 24. Cyclic voltammetric studies reveal that the reduction waves of the fluorenone, 9-[(4-pyridyl)methylene]fluorene and 9-[di(4-pyridyl)methylene]fluorene units endow oligomers with n-doping characteristics, with reversible reduction waves being observed for some compounds. The new aryleneethynylene oligomers have potential applications as molecular wires in practical devices.

Synthesis and conformational properties of cyanoethyl–Scleroglucan

Cyanoethyl derivatives were obtained as intermediates in the chemical modification of the neutral polysaccharide Scleroglucan, aimed at attaining new ionic carbohydrate polymers. The chemical and conformational properties of the cyanoethylated polymer were investigated and compared with those exhibited by the native one. In particular, capillary viscosity and small angle X-ray scattering experiments demonstrated that in aqueous solutions cyanoethyl derivatives were not able to assume the triple helix structure typical of the parent sclecroglucan.

SYNTHESIS OF SOME NEW HETEROCYCLIC COMPOUNDS FROM BENZOPYRANO[2,3-c]PYRAZOL-3-ONE DERIVATIVES

The reaction of benzopyrano[2,3-c]pyrazol-3-one (1) with some active halo compounds, afforded compounds 4, 8 and 12, respectively. The cyanoethyl derivative 19 was synthesized and treated with active methylenes and sulfur or benzoylisothiocyanate and phenacyl bromide, to give compounds 24a,b and 27. Compounds 25a,b and 28 were obtained through the reaction of compounds 24a,b with acrylonitrile or compound 27 with maleic anhydride. Thiation of compound 1 afforded the corresponding thio derivative 29. The reaction of 4-benzylidene-2-methyloxazolin-5-one with compounds 1 or 29 gave products 30a,b , respectively.

Thermotropic mesomorphism of selected (2-hydroxypropyl)cellulose derivatives

The thermotropic mesomorphism of some cellulose derivatives (CD) based on the (2-hydroxypropyl)cellulose (HPC) was investigated. Three types of derivatives: two esters (PPC, HxPC) and cyanoethyl derivative (CEPC) were prepared. The X-ray diffraction patterns of CDs were compared with the differential scanning calorimetry, thermooptical, and mechanical measurements within a broad range of the temperature. Two relaxation processes αa and αm, observed in the solid state of HPC, are also exhibited by all CDs, however, at lower temperatures. The αm relaxations, which indicate the transition from frozen anisotropic phase to mobile liquid crystalline (LC)-phase, are shifted towards the lower temperatures with a corresponding increase in the d-spacing of the poly(saccharide) main chains of CDs (as seen in the X-ray measurements). The transition temperature to isotropic phase Tni as well as glass transition temperature Tg (αa-relaxation) of the investigated CDs depend on the interactions between the lipophilic side chains and the hydrophilic poly(saccharide) main chains of CDs. These interactions are determined by the length and polarity of the lipophilic side chains. The observed changes in the transition temperature to isotropic phase Tni for CDs is consistent with the assumption that LC-organization of the poly(saccharide) main chains is stabilized by the lipophilic side-chains system. A significant increase in the length of the lipophilic side chains leads to nonlinear conformation, thus reducing the influence of van der Vaals forces, and consequently lowering Tni. The polymer with high polarity lipophilic side chains (CEPC) exhibits higher Tni in comparison to the ester derivative PPC with the same length of the side chains but having lower polarity. The stabilization effect of the lipophilic side-chains system on the LC-organization of the poly(saccharide) main chains is determined by the dynamic balance between length and polarity of the lipophilic side-chains system. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 76: 837–844, 2000

ChemInform Abstract: Preparation and Surface Active Properties of Alcohol Ethoxylates with an Amide Oxime Terminal Group.

AbstractBase‐catalyzed cyanoethylation of polyglycol ethers such as (III) gives the cyanoethyl derivative (V) which reacts with free hydroxylamine (VI), forming the amidoxime (VII).

(α-Pyridyl) methyl phosphoro-bis-triazolide as a new phosphorylating reagent for internucleotide bond formation

(α-Pyridyl)methyl phosphoro-bis-triazolide has been found to be a reagent of choice for phosphate protection in oligodeoxyribonucleotide synthesis. The reagent has been used successfully to phosphorylate all the four 5’-and N-protected deoxynucleosides. The resulting 3′-phosphorylated derivatives were found to be fairly stable as either triethyl ammonium salts or cyanoethyl derivatives. The phosphorylated derivatives were used in the preparation of the dimers TpT and d(ApT) in solution phase and a tetramer, TTTT, and a hexamer, d(ATATAT), on solid phase using glass support. The method gave excellent yields. Considerably reduced condensation time (6–9 min) and practically no cleavage of the internucleotide bond during the removal of the group are the advantages.

Molecular structure of the cis‐syn photodimer of d(TpT) (cyanoethyl ester)

AbstractThe three‐dimensional structure was determined by x‐ray crystallography for d(T[p](CE)T), a uv photoproduct of the cyanoethyl (CE) derivative of d(TpT), having the cis‐syn cyclobutane (CB) geometry and the S‐configuration at the chiral phosphorus atom. The crystals of C23H30N5O12P · 2H2O belong to the orthorhombic space group P212121 (Z = 4), with cell dimensions a = 11.596 Å, b = 14.834 Å, and c = 15.946 Å, containing two water molecules per asymmetric unit. The CB ring is puckered with a dihedral angle of 151°. The two pyrimidine bases are rotated by –29° from the position of direct overlap of their corresponding atoms. This represents a major distortion of DNA, since in DNA adjacent thymines are rotated by +36°. The pyrimidine rings are puckered with Cremer–Pople parameters for T[p] and in parentheses [p]T: Q: 0.24 Å (0.31 Å); θ: 123° (120°); ϕ: 141° (86°). These represent half‐chairs designated as 6H1 (T[p]) and 6H5 ([p]T). The CB and pyrimidine ring conformations are interrelated, and we postulate that they execute a coupled interconversion in solution. The T[p] segment has the syn glycosyl conformation, a 2T3 sugar pucker, and gauche− conformation at C4′‐C5′; the [p]T segment is anti, 3T4, trans. The C5′‐O5′ torsion of the [p]T unit is –124.5°, and the C3′‐O3′ torsion of the T[p] unit is –152.9°. Bond angles and bond lengths involving the phosphorus atom are similar to those of other phosphotriesters. The P‐O3′ and P‐05′ torsion angles are –138.1° and 58.6°, respectively. Several intermolecular (but no intramolecular) hydrogen bonds are found in the crystal.

Mutagenicity to Salmonella of the mono methylamino and N-cyanoethyl analogues of 4-dimethylaminoazobenzene (DAB) and 6-dimethylaminophenylazobenzthiazole (6BT).

Replacement of one of the methyl groups of the carcinogens 4-dimethylaminoazobenzene (DAB) and 6-dimethylaminophenylazobenzthiazole (6BT) with a cyanoethyl (-CH2CH2CN) substituent dramatically increases their mutagenic potency to Salmonella (strain TA98). The corresponding monomethylamino derivatives (-NHCH3) are more mutagenic than the parent dimethylamino [-N(CH3)2] compounds, but substantially less mutagenic than the cyanoethyl derivatives. All of these mutagenic activities are liver-S-9-dependent. The very similar dose response curves observed for the two cyanoethyl compounds argues for the formation of a common electrophilic intermediate from each.

Investigation of the stereochemical direction of the cyanoethylation of six-membered heterocyclic ketones as a function of the nature of the heteroatom

Only a mono (cyanoethyl) compound is formed from thiopyranone in the cyanoethylation of six-membered heterocyclic ketones that contain a methyl group attached to the C2 atom of the heteroring, whereas primarily bis- and tris(cyanoethyl) derivatives are obtained from pyranone due to the effect of the heteroatom.

Cyanoethylation of some dimethyl- and trimethylphenols

Cyanoethylation of some dimethyl- and trimethylphenols in acidic and basic media has been investigated. The cyanoethyl derivatives obtained were hydrolysed to the corresponding acids which on cyclisation with PPA afforded either dihydrocoumarin or chromanone whose structures were assigned on the basis of chemical and spectral evidence.

CVII. Total synthesis of the structural gene for an alanine transfer ribonucleic acid from yeast. Synthesis of a dodecadeoxynucleotide and a hexadeoxynucleotide corresponding to the nucleotide sequences 1 to 12

A dodecadeoxynucleotide having the sequence, d-T-G-G-T-G-G-A-C-G-A-G-T, and a hexanucleotide having the sequence, d-C-C-A-C-C-A, have been chemically synthesized. These compounds represent, respectively, the nucleotide sequence 1 to 12 of one strand and 1 to 6 of the complementary strand of the gene corresponding to yeast alanine transfer RNA. The synthesis of the dodecanucleotide started with the condensation of 5′- O-monomethoxytrityl thymidine (d-MMTr-T) with N-benzoyl-3′- O-acetyl deoxyguanosine 5′-phosphate (d-pg BZ- OAc) to give the dinucleotide, d-MMTr-TpG BZ. Successive condensations of suitability protected mononuoleotides with the 3′-hydroxyl end of the growing chain gave the protected heptanucleotide, d-MMTr-TpG BZpG BZpTpG BZpG BZpA BZ. The protected heptanucleotide was then condensed with the dinucleotide, d-pC ANpG BZ- OAc, to give the nonanucleotide, d-MMTr-TpG BZpG BZpTpG BZpG BZpA BZpC ANpG BZ. Condensation of the nonanucleotide with the protected trinucleotide, d-pA BZpG BZpT- OAc, gave the protected dodecanucleotide, d-MMTr-TpG BZpG BZpTpG BZpG BZ-pA BZpC ANpGr BZpA BZpG BZpT. The condensing agents used were dicyclohexylcarbodiimide, tri-isopropylbenzenesulfonyl chloride and mesitylenesulfonyl chloride. After removal of the protecting groups, the completely deprotected dodecanucleotide was further purified by anion-exchange chromatography in the presence of 7 M-urea. The steps involved in the synthesis of the hexanucleotide were: the condensation, of 5′- O-cyanoethyl phosphate of N (4)-anisoyl deoxycytidylyl-(3′ → 5′)MN (4)aniaoyl deoxycytidine, d-CEpC AnpC An, with d-pA BZ- OAc to give the protected trinucleotide, d-pC AnpC AnpA BZ, and the condensation of cyanoethyl derivative of the trinucleotide (d-CEpC AnpC AnpA BZ) with the trinucleotide, d-pC AnpC AnpA BZ- OAc, to give the protected hexanucleotide, d-pC AnpC AnpA BZpC AnpC AnpA BZ. After removal of the N-protecting groups the 5′-phosphate group was removed by treatment with bacterial alkaline phosphatase and the hexanucleotide, d-C-C-A-C-C-A, was isolated by paper chromatography. The yields varied between 20 and 80% at different steps.