Reactions of diazocyclopropane with hydrogenated and cyclopropanated levoglucosenone analogs

Diazocyclopropane attacks the carbonyl group of 6,8-dioxabicyclo[3.2.1]octan-4-one or 7,9-dioxatricyclo[4.2.1.0^2,4]nonan-5-one, saturated derivatives of levoglucosenone, to form the corresponding stereoisomeric oxaspiropentanes. In the case of the strained tricyclononane, 5R-isomer isomerizes under the reaction conditions into spiro-fused cyclobutanone. For this ketone, the formation of homologation products, i.e., the respective regioisomeric spiro-[8,10-dioxatricyclo[5.2.1.0^2,4]decane-6(5),1′-cyclopropan]-5(6)-ones, is also observed.     

Dehydrohalogenation of adducts of dichlorocarbene with cyclooctene and its peripherally cyclopropanated analogs

Dehydrohalogenation of three isomeric adducts of dichlorocarbene with bicyclo[6.1.0]non-1-,-2-, and-4-enes under the action of potassiumtert-butoxide in DMSO was studied. In the course of dehydrohalogenation of the substrates under study, different isomerization processes, which were accompanied by repeated migrations of multiple bonds that formed, occurred depending on the structure of dichlorides, while no skeletal rearrangements were observed. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 938–942, May, 1999.     

Synthesis of 23-ketocholestane derivatives with different side-chain lengths (asterosapogenin analogs)

Syntheses were developed for 23-ketoasterosapogenin analogs with various sidechain lengths from dimethyl(tert-butyl)silyloxypregnenolone (DMTBS-pregnenolone) through 20-hydroxy-23-carboxylates or 22-acetylenic (C₅, C₆) derivatives by reduction and allylic rearrangement with concurrent oxidation of the intermediate 23-hydroxy-27-nor- and 27-nor-26-methylcholestanes.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 965–969, April, 1991.     

Design,synthesis, and anti-TMV bioactivities of nucleobase phosphonate analogs

A series of novel nucleobase derivatives and their analogues possessing diethoxyphosphoryl scaffolds were synthesized through four-step reactions and screened for their antiviral activity toward tobacco mosaic virus (TMV). Preliminary bioassays suggested that some of these simple structures displayed appreciable anti-TMV activity in vivo. Among them, compound (diethoxyphosphoryl)methyl 4-[2-(1H-benzo[d][1,2,3]triazol-1-yl)acetamido]-benzoate (a-3) exerted the strongest chemotherapeutic and protective effects against TMV with the rates of 52.8 and 72.2% at the dosage of 500 µg/mL, respectively, which were comparable with those of the commercial agricultural antiviral agent ningnanmycin (54.2 and 70.2%). Molecular docking with TMV helicases revealed that compound a-3 had strong interactions with receptor amino acid residues. Given the facile synthetic route and significant chemotherapeutic and protective potentials, compound a-3 could be further studied and exploited as a promising antiviral candidate.     

Synthesis ofd-provitamins containing a side-chain isozazoline ring

This is the first report of the synthesis of 20-isoxazoline steroids containing a 5,7-diene group by 1,3-dipolar cycloaddition of nitrile oxides to Δ²²-steroids, leading to 20-isoxazolin-5′-ylsteroids, or of steroidal 22-nitrile oxides to low-molecular-weight dipolarophiles, giving 20-isoxazolin-3′-ylsteroids. Institute of Bioorganic Chemistry, Academy of Sciences of Belarus, 220141 Minsk, Belarus. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 267–273, February, 1998.     

Synthesis of cyclopropanated [2.2.1] heterobicycloalkenes: An improved procedure

A safer and improved method to our previous report on palladium-catalyzed cyclopropanation of heterobicyclic alkenes has been developed. By using tetrahydrofuran as the solvent and a more dilute aqueous NaOH solution for the generation of diazomethane from Diazald, cyclopropanation could be achieved smoothly with minimal adjustment over the course of reaction. 7-Oxabicyclic substrates with bulky C1 or C2 groups, as well as 2,3-diazabicyclic substrates with various N-substituents, effectively underwent cyclopropanation. Using this methodology, yields to previously reported products were markedly increased, and 10 new cyclopropanated [2.2.1] heterobicyclic products were prepared. In addition, this work accounts for the first reported cyclopropanation of 2,3-diazabicyclic alkenes, which all gave excellent yields of >90%.     

Design and synthesis by click triazole formation of paclitaxel mimics with simplified core and side-chain structures

A library of paclitaxel (taxol) mimics was obtained by a straightforward strategy involving rational design and an efficient synthesis of a simplified taxane core substitute, together with a click-chemistry combinatorial search for phenylisoserine side-chain surrogates.     

Synthesis of side-chain monofluorinated amphetamines

R- and S-2-Amino-3-fluoro-1-phenylprupane were prepared in approximately 50% yields by the action of HF-pyridine on R- and S-2-benzylaziridine. (±)-2-Amino-3-fluoro-1-(4-chlorophenyl)propane was similarly prepared from (±)-2-(4-chlorobenzyl)aziridine. Structures of products were confirmed by n.m.r. and mass spectroscopy. In contrast, when 2-benzyl-N-tosylaziridine was reacted with HF in pyridine, the C₂ atom of the aziridine ring was the site of fluorination and the N-tosylated derivative of 3-amino-2-fluoro-1-phenylpropane was obtained in excellent yield.     

姜黄素类似物的合成及其生物活性的测定

实验合成了姜黄素的Knoevenagel缩合物4-(2-呋喃次甲基)姜黄素C1,氨基硫脲Schiff 碱配体E1,及其Schiff 碱配体的Zn(Ⅱ)配合物D1.采用DPPH法测定了产品清除自由基的能力,结果表明产品C1对DPPH自由基清除率为82.0%.在pH7.2的Tris-Hcl缓冲溶液中,采用紫外光谱和荧光光谱研究了C1与鲱鱼精DNA的相互作用,结果表明,C1与DNA是通过嵌插模式发生相互作用的,其键合常数为Kq =9.31×103.     

Synthesis and bioactivities of diamide derivatives containing a phenazine-1-carboxamide scaffold

Taking natural product phenazine-1-carboxamide (PCN) as a lead compound, a series of novel phenazine-1-carboxylic acid diamide derivatives were designed and synthesised. Their structures were confirmed by ¹H-NMR and HRMS. The bioassays showed that some of the target compounds exhibited promising in vitro fungicidal activities, and exhibited excellent and selective herbicidal activities. Particularly, compounds c, h, o and s displayed root length inhibition activities against barnyard grass with the rate of more than 80%. Compound c exhibited the best activity among all the target compounds against barnyard grass stalk length with the IC₅₀ value of 0.158 mmol/L, and compound o exhibited the best and wide spectrum inhibition against barnyard grass root length and rape in both root length and stalk length herbicidal activities with its IC₅₀ values of 0.067, 0.048 and 0.059 mmol/L respectively. The analysis of preliminary Structure-Activity Relationships provides the theoretical basis for further design of phenazine-1-carboxylic acid.     

Synthesis and bioactivities of phenazine-1-carboxylic piperazine derivatives

Abstract

Phenazine-1-carboxylic acid (PCA) as a natural product which has significant inhibition effects against many soil-borne fungal phytopathogens in agricultural application and has been registered in China as the fungicide against rice sheath blight. In order to find new higher fungicidal activities lead compounds and develop new eco-friendly agrochemicals, we introduced substructure piperazines which also have high biological activity into PCA, designed and synthesized a series of phenazine-1-carboxylic piperazine derivatives, and their structures were confirmed by ¹H NMR and HRMS. Most compounds exhibited certain in vitro fungicidal activities. In particular, Compounds 5r exhibited the activity against all the tested pathogenic fungi, such as Rhizoctonia solani, Alternaria solani, Fusarium oxysporum, Fusarium graminearum, Pyricularia oryzac Cavgra, with the EC₅₀ value of 24.6μM, 42.9μM, 73.7μM, 73.8μM, 34.2μM, respectively, more potent activities than PCA (33.2μM, 81.5μM, 186.5μM, 176.4μM, 37.3μM). This result provided a highly active lead compound for the further structure optimization design.     

Synthesis and antiviral bioactivities of alpha-aminophosphonates containing alkoxyethyl moieties

A simple, efficient, and general method has been developed for the synthesis of various alpha-aminophosphonate derivatives 4a-4l by treatment of substituted benzaldehydes and aniline with bis(2-methoxyethyl)- or bis(2-ethoxyethyl) phosphite under microwave irradiation without solvents and catalysts. The products were characterized by elemental analysis, IR, 1H-NMR, 13C- and 31P-NMR spectra. The X-ray crystallographic data of the representative compound 4l was determined. The new alpha-aminophosphonate derivatives were found to possess moderate to good antiviral activity.     

Synthesis and bioactivities of steroid derivatives as antifungal agents

A series of lanosterol and cholesterol derivatives with modified side chain structures, which might interfere with sterol C24-methyltransferase in the ergosterol biosynthesis as substrate analogs, have been synthesized. The in vitro bioassay studies have shown that some of these compounds, in particular with C24-amino- and thio-functionalities, possess potent antifungal activities, in vivo. Bioassays have also been carried out for the leading compounds.     

Synthesis and characterization of azobenzene-containing side-chain photorefractive polymers

The synthesis and characterization of some new high-T_g photorefractive polymers, polyphosphazene P3-P8, were described. They were obtained via a post-azo coupling reaction. The resulting materials have been characterized by means of ¹H NMR, ³¹P NMR, FT-IR, UV-vis, GPC and DSC. Chromophore contents up to 14 mol% have been realized. The polymers had high glass transition temperatures and good optical transparency. Measurements reveal that they possess relatively large magnitude of photoinduced birefringence.     

Synthesis and hydrolysis behavior of side-chain functionalized norbornenes

[reaction: see text] The stabilities of various functionalized norbornenes that are monomers for the ring-opening metathesis polymerization (ROMP) in aqueous solution were evaluated toward hydrolysis under a range of temperatures (37, 60, and 80 degrees C) and pH values (3-9). All monomers contain hydrolyzable linkages to pendant functional groups, and conclusions were drawn relating to how the chemical diversity of these pendant functional groups, in accordance with the pH and temperature variations, affect hydrolysis of the aforementioned linkages. The hydrolysis was monitored by reverse phase HPLC analysis, and/or NMR spectroscopy. As expected, monomers containing ester linkages were fairly labile at higher pH values, while acetal-based linkers were cleaved at lower pH values. Beta-amino ester groups experienced a significant increase in hydrolysis rate, while carboxylic acid-containing monomers did not follow any clear trend. Saccharide-containing monomers exhibited unique behaviors for various pH values and temperature ranges.     

Synthesis and characterization of side-chain liquid crystal polyurethanes

A series of liquid crystal α-[bis(2-hydroxyethyl)amino]-ω-(4-nitroazobenzene-4′-oxy)alkanes (Cn-diol) with different alkyl chain length has been synthesized. All Cn-diols exhibit a smectic phase that has been identified by means of polarizing microscopy and differential scanning calorimetry. These compounds are suitable monomers for the synthesis of side-chain liquid crystalline polyurethanes and polyesters. They were polymerized with hexamethylene diisocyanate to corresponding SCLC polyurethanes in which the spacer length was varied from 2 to 12 methylene units. Polyurethanes (CnP) with spacer lengths n ≥ 4 exhibited liquid crystalline behavior. Fourier transform infrared temperature studies of the CnP were done focusing on H-bonds between the N H and CO groups of the urethane backbone. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 2871–2888, 1997     

One-step synthesis of paclitaxel side-chain precursor: benzamide-based asymmetric aminohydroxylation of isopropyl trans-cinnamate

A highly enantioselective (up to 97% ee) one-step synthesis of paclitaxel side chain precursor, (2R,3S)-isopropyl 3-benzamido-2-hydroxy-3-phenylpropionate, has been achieved by osmium-catalyzed asymmetric aminohydroxylation of isopropyl trans-cinnamate with N-bromobenzamide as an oxidant/nitrogen source in the presence of (DHQ)₂PHAL as a chiral ligand. Simple recrystallization of crude product (containing regioisomer and diol) from ethyl acetate gave the enantiomerically pure product.     

Synthesis of novel multi-arm star azobenzene side-chain liquid crystalline copolymers with a hyperbranched core

A series of novel multi-arm star side-chain liquid crystalline (LC) copolymers with hyperbranched core moieties were synthesized by atom transfer radical polymerization (ATRP) using a multi-functional hyperbranched polyether as the initiator and chlorobenzene as the solvent. The multi-functional hyperbranched polyether initiator was prepared from poly(3-ethyl-3-(hydroxymethyl)oxetane) (PEHO) and 2-bromo-2-methylpropionyl bromide. The azobenzene side-chain liquid crystalline arms were designed to have an LC conformation of poly[6-(4-methoxy-4^′-oxy-azobenzene)hexyl methacrylate] with different molecular weights. Their characterization was performed with ¹H NMR, size exclusion chromatograph (SEC), differential scanning calorimetry (DSC) and thermal polarized optical microscopy (POM). The multi-arm star side-chain liquid crystalline copolymers exhibited a smectic and a nematic phase, and the phase transition temperatures from the smectic to the nematic phase and from the nematic to isotropic phase increased with increasing the molecular weight of the multi-arm star side-chain liquid crystalline copolymers from 1.78 × 10⁴ to 9.07 × 10⁴.     

Synthesis of analogs of a tetrapepside of gastrin with a modified tryptophan residue

Summary New derivatives of the COOH-terminal tetrapeptide of gastrin containing in place of the tryptophan residue the acyl radicals -(1-naphthyl)acryloyl, -(1-naphthyl)propionyl, -(2-naphthyl)propionyl, and -benzyloxycarbonylamino--(1-methylindol-3-yl)propionyl have been synthesized.Institute of Organic Synthesis, Academy of Sciences of the Latvian SSR. Translated from Khimiya Prirodnykh Soedinenii, No. 4, pp. 498–503, July–August, 1971.