Synthesis and properties of siRNAs containing 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleosides

Short interfering RNAs (siRNAs) containing P3′→N5′ phosphoramidate linkages were successfully synthesized by introducing 2′-deoxy-2′-fluororibonucleoside and 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleoside in succession. It was found that the introduction of 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleosides into siRNAs improved the nuclease-resistant properties of the siRNAs without loss of their silencing efficacy.     

Synthesis of 2′-β-C-methyl-neplanocin derivatives as anti-HCV agents

The synthesis of 2′-β-C-methyl-neplanocin derivatives is described. The key intermediate cyclopentenyl alcohol 12 is prepared from sugar 5 in 12 steps. Coupling of 12 with appropriately protected purine, 7-deaza pyrimidine, uracil and pyrimidine bases via the Mitsunobu reaction followed by deprotection afforded the target cyclopentenyl nucleosides (18-23, 27). The synthesized compounds were evaluated as potential inhibitors of the hepatitis C virus (HCV) in vitro. Unfortunately, none of them show anti-HCV activity below EC₅₀ 100 μM.     

Oxidizing mechanism of podophyllotoxin and its derivatives by sodium persulfate

The oxidizing mechanism of podophyllotoxin and its derivatives by sodium persulfate has been studied by laser flash photolysis and pulse radiolysis. The formation and decay processes of transient species of podophyllotoxin and its derivatives have been observed, and a series of rate constants for the formation and decay of transient species have been determined. It has been found that there is a light (UV) sensitive group on the C-4 of podophyllotoxin and two light (UV) sensitive groups on the C-4 and C-4' of 4'-demethylepipodophyllotoxin.     

Synthesis of benzocycloheptanones through coupling of δ,ε-unsaturated chromium carbene complexes and 2-alkynylbenzoyl derivatives

The coupling of pentenylcarbene complexes and 2-alkynylbenzoyl derivatives affords naphthocycloheptanones in a single step involving simultaneous construction of both the seven-membered ring and one of the aromatic rings. Aryl tethered systems undergo intramolecular cyclopropanation.     

Synthesis and photo-physical properties of methoxy-substituted π-conjugated-2,2′-bipyridines

4,4′-Bis-vinyl-2,2′ bipyridines have been known in the area of materials chemistry since last few decades. Bipyridine molecules bearing donor substituents in their π backbone are examples of ‘push-pull’ molecules. Emissive properties of such ligands depend on the position of the donor unit in their π backbone. The Horner-Wordsworth-Emmons reaction has been used extensively to synthesize such types of conjugated systems. Three newly synthesized highly conjugated 2,2′ bipyridines (3a-c) have been described. The molecules 3a-c are highly emissive in the visible region at room temperature.     

Metal catalysed reactions of β,β′-tricarbonyl derivatives with isocyanates

The reactions of β,β′-tricarbonyl derivatives with isocyanates are catalysed by 2 mol % transition metal acetylacetonates (e.g., [Co(acac)₂] and [Zn(acac)₂]) at room temperature. 3-Oxo-1,5-pentanedioic acid dimethylester (1) reacts with RNCO (R=Et, CH₂CHCH₂, CH₂Ph, Ph, 4-Cl-Ph) to give 1:1 adducts involving the formation of a new C-C bond between the intercarbonylic methylene and the isocyanato group. Under similar conditions 2,4,6-heptanetrione (2) reacts with the same isocyanates to afford pyridinone and pyranone derivatives resulting from the cyclisation of unstable 1:1 and 1:2 adducts.     

Selective alkylation/oxidation of N-substituted isoindolinone derivatives: Synthesis of N-phthaloylated natural and unnatural α-amino acid analogues

The interchangeability of the isoindolinone group as a nitrogen protecting group for amino acid intermediates is demonstrated by the preparation of several natural and unnatural α-amino acid derivatives using a two-carbon N-isoindolinone (phthalimidine) scaffold. Using a selective benzylic oxidation, the N-isoindolinone group is then converted to the N-phthaloyl group for convenient removal (65–98%). For preparation of the isoindolinone products which were to be the substrates for benzylic oxidation, a range of side chains were installed on the isoindolinone-protected glycine equivalent on deprotonation to demonstrate the utility of the N-protected isoindolinone synthon (51–93%). While the ensuing benzylic oxidation is employed successfully for converting the N-isoindolinone group to the N-phthaloyl group in simple substrates, substrates bearing unsaturated or electron-rich side chains respond poorly to the oxidation.     

Synthesis and reactions of sulfur-substituted α,β-unsaturated δ- and γ-lactones

A new synthetic method for the preparation of sulfur-substituted α,β-unsaturated δ- and γ-lactones has been developed by reaction of the allylic bromides of 5,6-dihydro-2-pyridinones with NaOH in refluxing MeOH or t-BuOH. The substituents at C5 and C6 of these substrates are very important for the success of this reaction. Some synthetic transformations of the α,β-unsaturated δ-lactones have also been carried out.     

Synthesis of azo derivatives of 4-aminosalicylic acid

For searching a better 4-aminosalicylic acid derivative with higher activity and less side effects against the inflammatory bowel disease, 4-aminosalicylic acid (4-ASA) was protected by benzyloxycarbonyl and acetyl, respectively. The resultant was hydrogenized to remove protective group of amino group, then the product was reacted with NaNO2 to give diazonium salt, which was conjugated with salicylic acid, hydroxybenzene, TV-salicyloyl glycine acid to get azo derivatives of 4-ASA. The azo derivatives were hydrolyzed under the alkaline condition to get the target products. All compounds were characterized by FT-IR, 1H NMR, 13C NMR spectra in details. New derivatives of 4-ASA were characterized. The synthetic route was reasonable and feasible.     

Synthesis and properties of furan derivatives. 3. Synthesis of 1,2-disubstituted δ2-imidazolines containing furfuryl and tetrahydrofurfuryl groups

The condensation of N-furfuryl- and N-tetrahydrofurfurylethylenediamines with hydrochloride salts of iminoesters of carboxylic acids gives 1,2-disubstituted ²-imidazolines containing furfuryl or tetrahydrofurfuryl groups at N¹.For communication 2, see [1]Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1312–1315, October, 1992.     

Reaction of 2-alkoxycarbonylmethyl derivatives of δ2-oxazoline and δ2-imidazoline and their tautomers with 4-nitrobenzonitrile N-oxide

It was established that 2-alkoxycarbonylntethylene derivatives of oxazolidine and imidazolidine react readily with 4-nitrobenzonitrile N-oxide; the reaction takes place at the methylidyne carbon atom to give intermediate oximes, which can then undergo cyclization to isoxazoles. Their tautomers —benzimidazole and ² -oxazoline derivatives —react with considerably greater difficulty; in the first case the reaction takes place at a different center, viz., the ring nitrogen atom.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 681–684, May, 1991.     

Synthesis and characterization of water-swellableα,β-polyasparthydrazide derivatives

The synthesis of a new crosslinked polymer by reaction of , -polyasparthydrazide and glutaraldehyde is reported. Different crosslinking degrees were obtained by varying the ratio between the aldehyde and the starting polymer. The crosslinked polymer was characterized by water swelling tests and thermal analysis. In particular, the crosslinking density and its effects on the glass transition temperature of the material were studied. Finally, the microstructure of the obtained polymer was observed using scanning electron microscopy.     

Synthesis and characterization of water-swellableα,β-polyasparthydrazide derivatives

, -polyasparthydrazide (PAHy) was crosslinked by glutaraldehyde to form water-swellable materials possessing a three-dimensional molecular network. Different crosslinking degrees were prepared varying glutaraldehyde/PAHy ratio and samples containing 5-fluorouracil were obtained by incorporating the drug into the polymer networks during the crosslinking reaction. All samples were characterized by swelling tests, thermal, x-ray and SEM analysis. Their microstructure was observed through scanning electron microscopy. Furthermore, for samples containing the anticancer drug,in vitro release studies were performed in pH 7.4 buffer solution.     

Synthesis ofN-chioroacetyl-β-glycopyranosylamines,derivatives of monosaccharides and lactose

N-Chloroacetyl--glycopyranosylimines were synthesized from various monosaccharide (hexoses, pentoses, deoxysugars, uronic acids, and sugar phosphates) and a disaccharide (lactose) byN-acylation of the corresponding -glycosylamines with chloroacetic anhydride in DMF In some cases, treatment of rnonosacc harides with NH₃ in the presence of (NH₄)₂CO₃ in MeOH or aqueous MeOH was more efficient than the methods previously described, as it gave -glycosylarnines in higher yields.Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 7, pp. 1848–1851, July, 1996.     

Synthesis of γ-benzyltert-butoxycarbonyl-L-alanyl-D-glutamate and its derivatives

A convenient method of obtaining Boc-L-Ala-D-iGln-OBzl and its amide analogs by condensing the N-hydroxysuccinimidyl ester of Boc-L-Ala with the -benzyl ester ofD-Glu in the presence of NaHCO₃, followed by amidation of the resulting Boc-L-Ala-D-Glu--OBzl, is proposed. The use of l-adamantylamine and octadecylamine as amino components has enabled the corresponding -adamantylamide and octadecylamide of the dipeptide to be obtained.Simferopol' State University, 4 Yaltinskaya ul., Simferopol', Crimea, Ukraine 333036. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 101–103, January–February, 1998.     

Synthesis and evaluation of new phosphonated δ-lactam and glutarimide derivatives as angiotensin converting enzyme inhibitors

An efficient synthesis of new γ,δ-insaturated δ-lactam and glutarimide derivatives bearing a phosphonomethyl group from a common allylphosphonate precursor is described. Our approach is based on a two-step procedure involving the preparation of phosphonated-1,5-ketoester and −1,5-diester followed by an amidation–heterocyclization sequence. The first step proceeds via Michael's addition of ethyl acetoacetate and diethyl malonate on an allylphosphonate starting material. The second step consists of a base-promoted intramolecular amidation-cyclization sequence with primary amines, which accounts for the construction of δ-lactams and glutarimide skeletons. We performed the evaluation of angiotensin I-converting enzyme (ACE) inhibition using an in vitro enzyme assay on six new compounds. Five compounds showed potent ACE inhibitory activity, with IC₅₀ values ranging from 0.02 to 0.27 mg/ml. Compared with Captopril, used as a reference drug, two new glutarimide derivatives exhibited higher efficiency ACE inhibition activity.     

Anticancer Drugs (VI)——Synthesis and Activity of Spin Labeled Derivatives of 4-Amino-4-deoxy-4′-demethylepipodophyllotoxin

Some derivatives of podophyllotoxin(1), such as etoposide(12), possess antitumor activity and have been extensively used clinically^[1]. Because etoposide has a less solubility in water and higher toxicity, many chemists have an interest in further studies on the modification of the C-4 substituent of 1 for its better antitumor activity. Lee Kuo-hsing, Wang Zhe-qing et al. have synthesized a series of derivatives of CA (substituted anilino)-4-deoxypodophllotoxin. The pharmaceutical tests have shown that a number of 4β-(arylamino )-4'-demethylepi-podophyllotoxin are as potent as or more potent than etoposide(12) in inhibiting the human DNA topoisomerase Ⅱ.     

Synthesis and electroluminescent properties of naphthalimide derivatives

Naphthalimide derivatives, N-ethyl-4-acetylamino-l ,8-naphthalimide (EAAN) and polymer with N-propyl-4-acetylamino-l,8-naphthalimide (PAAN) side-chain (P-PAAN) were successfully synthesized. Electroluminescent devices of ITO/PVK(120nm)/EAAN(50nm)/Al(150nm) (Ⅰ) and ITO/PVK P-PAAN( 10:1) (50nm)/Al(150nm) (Ⅱ) constructed with EAAN and P-PAAN as the emitting layer were investigated, whereas the single-layer devices of ITO/EAAN or P-PAAN(50nm)/Al(l50nm) (Ⅲ) were not observed to have any e-mission light. The emission results revealed that the exciton recombination formed by positive and negative charge carriers injected from electrodes of devices Ⅰ and Ⅱ was much more balanced than that of devices Ⅲ, which implied that naphthalimide derivatives are a new type of electron-transporting materials with high performance. The electron-transporting properties of naphthalimide derivatives were also elucidated by investigation of the electroluminescent behaviors from both devices of ITO/PPV (80nm)/Al and ITO/P     

Total synthesis of bioactive drimane–epoxyquinol hybrid natural products: macrophorin A, 4′-oxomacrophorin A,and 1′-epi-craterellin A

Total synthesis of novel hybrid natural products, merosesquiterpenoids macrophorin A, 4′-oxomacrophorin A, and 1′-epi-craterellin A has been accomplished following a general strategy based on a sacrificial Diels–Alder–retroDiels–Alder approach to control regio- and stereoselectivity.     

Synthesis and properties of β,β-sp3-hybridized subphthalocyanine analogues

A β,β-sp(3)-hybridized subphthalocyanine analogue, dibenzosubtriazachlorin, was synthesized, and its significantly split Q band absorptions in longer and shorter wavelength regions relative to those of subphthalocyanines were revealed. The effect of benzo-annulation to a subtriazachlorin structure on the position of the split Q bands as well as the electronic structures was also investigated.