Synthesis of the macrocyclic spermidine alkaloids oncinotine, neooncinotine, isooncinotine and pseudoonicotine in racemic forms (author's transl)]

Synthesis of the Macrocyclic Spermidine Alkaloids Oncinotine, Neooncinotine, Isooncinotine and Pseudooncinotine in Racemic Forms . The four isomeric spermidine alkaloids (Scheme 1) mentioned in the title were synthesized as follows: Reaction of the piperidine derivative 5 and the bromide 6 led to the intermediate 13 which was converted to (±)-oncinotine (±- 1 ) and (±)-pseudooncinotine (±- 4 ) (Scheme 3). The analogous reaction of 5 and the isomeric bromid 7 gave the intermediate 22 from which (±)-neooncinotine (±- 2 ) and (±)-isooncinotine (±- 3 ) were synthesized (Scheme 4). The overall yields were found to be between 22 (±- 1 ) and 54% (±- 3 ).     

Synthesis of (±)-O-methylcannabichromene and some homologues

A facile novel synthesis of (±)-O-methylcannabichromene ( 5d ) together with (±)-2-methyl-2-(4-methyl-3-pentenyl)-5-methoxy-2H-benzopyran ( 5a ) and its 7-methyl ( 5b ) and 7-propyl ( 5c ) homologues, using organolithium salts is described.     

Face Selectivity in the Diels-Alder Additions and Chelotropic Addition of Sulfur Dioxide to 2-(D)Methylidene-3-methylidenebicyclo[2.2.1]heptane

The stereoselectivity of the cycloadditions of 2-(D)methylidene-3-methylidenebicyclo[2.2.1]heptane ( 4 ) to various dienophiles has been determined. The exo- vs. endo-face selectivity depends on the type of dienophiles, and for olefinic ones, on the mode of attack (Alder- vs. anti-Alder endo rule). It is > 9:1 with N-phenyltriazolinedione (NPTAD) and ethylenetetracarbonitrile (TCNE), < 1:9 with dimethyl acetylenedicarboxylate (DMAD), 30 ± 5:70 ± 5 with DMAD in the presence of AlCl₃, 15 ± 5:85 ± 5 with dehydrobenzene and 40 ± 5:60 ± 5 with ¹O₂ generated photochemically (Table 1). With para-benzoquinone and maleic anhydride, the exo- vs. endo- face selectivity is < 1:9 and 20 ± 5:80 ± 5, respectively, for their anti-Alder mode of attack; it is 50 ± 5:50 ± 5 and 55 ± 5:45 ± 5, respectively, for their Alder mode of reaction. Under conditions of kinetic control, the chelotropic addition of SO₂ to 4 is endo-face selective.     

海水和大气中挥发性硫化物分析方法的研究

建立了大气和海水中挥发性硫化物的气相色谱分析方法,确定了最佳实验条件.为了适应不同的基质和保存方式,大气和海水样品采用了不同的分析方法.测定大气样品时,采用大气采样罐及三级冷阱预浓缩气相色谱-质谱联用技术,而海水样品采用吹扫捕集-气相色谱测定.本方法测定大气挥发性硫化物的线性范围较好,精密度为7.7%~15.1%,检出限为0.23~4.7 ng;海水中挥发性硫化物的精密度为3.5%~5.3%,检出限为2.5~3.5 ng.将本方法用于青岛近海海水和大气中硫化物的测定,测得海水中羰基硫、二甲基硫和二硫化碳的平均浓度分别为(268±58)pmol/L、(1264±0.2)pmol/L、(19±2)pmol/L,大气中的平均浓度为543±39、39±9和56±20(×10-12,V/V).本方法可准确测定海洋环境中的挥发性硫化物.     

Alpha spectroscopic analysis of actinides (Th,U and Pu) after separation from aqueous solutions by cation-exchange and liquid extraction

The radioactivity concentration of ²³⁶Pu, ²³²U and ²²⁸Th in aqueous samples has been determined by means of alpha spectroscopy after chemical separation and pre-concentration of the radionuclides by cation exchange and liquid–liquid extraction using the Chelex-100 resin and 30% TBP/dodecan, respectively. Method calibration using a ²³⁶Pu standard solution containing the daughter radionuclides results in a detector efficiency of 18% and in a chemical recovery for cation-exchange which is (30 ± 7)%, (90 ± 5)% and (20 ± 5)% for plutonium, uranium and thorium, respectively. The chemical recovery for liquid–liquid extraction is found to be (60 ± 7)%, (50 ± 5)% and (70 ± 5)%, for plutonium, uranium and thorium, respectively. The differences in the efficiencies can be ascribed to the oxidation states, the different actinides present in solution. Taking into account that the electrodeposition of the radionuclides under study is quantitative, the total method efficiency is calculated to be (18 ± 15)%, (46 ± 7)% and (15 ± 5)%, for plutonium, uranium and thorium, respectively, at the mBq concentration range. The detection limit of the alpha spectrometric system has been found to be 0.2 mBq/L, suggesting that the method could be successfully applied for the radiometric analysis of the studied radionuclides and particularly uranium in aqueous samples.     

A convenient stereoselective access to new bis-phosphorylated pyrrolidines and their corresponding nitroxides

Addition of one equivalent of dialkylphosphite to γ-diketones yielded new 5-phosphorylated 1-pyrrolines 3. Depending on the experimental conditions, the addition of a second equivalent of dialkylphosphite to 3, led either to (±)-2,5-bis-phosphorylated pyrrolidines 4 or a mixture of (±)- and meso-4. Pyrrolidines 4 were isolated and subsequently oxidized to the corresponding stable (±)- or meso-nitroxides, 5. Coupling of (±)-5a with the prochiral 2-phenyl-ethyl radical was investigated.     

Use of the electrophilic c-arylation by aryllead triacetates in the construction of synthons for aizoaceae and amaryllidaceae alkaloid synthesis

The vinylogous β-keto esters, ethyl 2-methyl-4-oxocyclohex-2-ene-carboxylate (Hagemann's Ester) (4), ethyl 4-oxocyclohex-1-ene-carboxylate (7a) and its double bond isomer (7b), undergo regiospecific arylation with aryllead triacetates at C1; reaction of the mixture of isomers (7a) and (7b) with aryllead compounds (5a), (5c) and (5d) provides intermediates for the synthesis of (±)-o-methyl-joubertiamine (1), (±)-mesembrine (2) and (±)?lycoramine (3) respectively.     

Vicinal Dianion of Triethyl Ethanetricarboxylate: Syntheses of (±)‐Lichesterinic Acid, (±)‐Phaseolinic Acid, (±)‐Nephromopsinic Acid, (±)‐Rocellaric Acid,and (±)‐Dihydroprotolichesterinic Acid

The vicinal dianion 2 derived from triethyl ethanetricarboxylate reacted regioselectively with aldehydes and ketones at C(β) to provide paraconic acid derivatives 5a – f in moderate to high yields as mixtures of diastereoisomers. The paraconic acid derivatives 5e and 5f were utilized as the starting materials for the syntheses of (±)‐lichesterinic acid ( 12 ), (±)‐phaseolinic acid ( 13 ), (±)‐nephromopsinic acid ( 14 ), (±)‐rocellaric acid ( 15 ), and (±)‐dihydroprotolichesterinic acid ( 16 ).     

Synthetic studies on arene-olefin cycloadditions-VIII. Total syntheses of (±)-silphiperfol-6-ene, (±)-7 α H-silphiperfol-5-ene and (±)-7 β H-silphiperfol-5-ene

Total syntheses of (±)-silphiperfol-6-ene, (±)-7 α H-silphiperfol-5-ene and (±)-7 β H-silphiperfol-5-ene are described in which a new element of stereoinduction in arene-olefin meta cycloadditions was tested and a new method for cycloadduct transformation was developed.     

Total Asymmetric Synthesis of Doubly Branched Carba-hexopyranoses and Amino Derivatives Starting from the Diels-Alder Adducts of Maleic Anhydride to Furfuryl Esters

The Diels-Alder adducts of maleic anhydride to furfuryl esters were reduced into 7-oxabicyclo[2.2.1]hept-5-ene-1,2-exo,3-exo-trimethanol (±)- 15 and enantiomerically pure (−)- 15 (Scheme 1). The tripivalate of (±)- 15 was converted into (1RS,2RS,3RS,4RS,5SR,6SR)-1,5,6-tris(hydroxymethyl)cyclohexane-1,2,3,4-tetrol ((±)- 23 ; Scheme 2). Reaction of BBr₃ with the triacetate (±)- 30 of (±)- 15 gave (1RS,2RS,5RS,6RS)-5-bromo-6-hydroxycyclohex-3-ene-1,2,3-trimethyl triacetate ((±)- 31 ) at −78°, and (1RS,2RS,5SR,8SR)-2-endo-hydroxy-6-oxabicylo[3.2.1]oct-3-ene-5,8-dimethyl diacetate ((±)- 32 ) at 0° (Scheme 3). Single-crystal X-ray diffraction of (1RS,2RS,5SR,8SR)-2-acetoxy-6-oxabicyclo[3.2.1]oct-3-ene-5,8-dimethyl diacetate ((±)- 33 ) was carried out. Displacement of bromide (+)- 31 (derived from (−)- 15 ) with azide anion gave (+)- 38 which was transformed into (+)-(1R,2R,5S,6S)-5-amino-6-hydroxycyclohex-3-ene-1,2,3-trimethanol ((+)- 40 ) (Scheme 4). Reaction of (±)- 31 with BBr₃ at 0°, followed by azide disubstitution led to (1RS,2RS,5SR,6SR)-5-amino-3-(aminomethyl)-6-hydroxycyclohex-3-ene-1,2-dimethanol ((±)- 45 ). Dihydroxylation of (±)- 38 and further transformations gave (1RS,2RS,3SR,4RS,5SR,6RS)-5-amino-1,4,6-trihydroxycyclohexane-1,2,3-trimethanol ((±)- 49 ) and (1RS,2RS,3SR,4RS,5SR,6RS)-2,3-dihydroxy-7-oxabicyclo[4.1.0]heptane-2,3,4-trimethanol ((±)- 55 ) (Schemes 5 and 6). Expoxidation of the 4-nitrobenzoate (±)- 61 of (±)- 38 allowed the preparation of (1RS,2RS,3SR,4RS,5RS)-5-amino-1,4-dihydroxycyclohexane-1,2,3-trimethanol ((±)- 65 ) and of (1RS,2RS,3SR,4RS,5SR,6RS)-5-amino-4-hydroxy-7-oxabicyclo[4.1.0]heptane-1,2,3-trimethanol ((±)- 67 ) (Scheme 7). The new unprotected polyols and aminopolyols were tested for their inhibitory activity toward commercially available glycohydrolases. At 1 mM concentration, 34, 30, and 31% inhibition of β-galactosidase from bovine liver was observed for (+)- 40 , (±)- 65 , and (±)- 67 , respectively.     

Total Synthesis of Racemic and Optically Active Compounds Related to Physostigmine and Ring-C Heteroanalogues from 3-[2′-(dimethylamino)ethyl]2,3-dihydro-5-methoxy-1,3-dimethyl-1H-indo l-2-ol

Oxindole 11 , obtained on 3-[2′-(dimethylamino)ethyl]alkylation of oxindole 12 , yielded, on stereoselective reduction with sodium dihydridobis(2-methoxyethoxy)aluminate, aminoalcohol 8 (Scheme 2). The quaternary methiodide 10 , obtained from 8 with MeI, gave, in nucleophilic displacements concurring with a Hofmann elimination, (±)-esermethole 6 , (±)-5-O-methylphysovenol ( 14 ), (±)-5-O-methyl-1-thiaphysovenol ( 15 ), and (±)-1-benzyl-1-demethylesermethole ( 16 ). Syntheses of (±)-1-benzyl-1-demethylphenserine ( 18 ), (±)-1-demethylphenserine ( 19 ), and (±)-phenserine ( 4 ) from 6 and 16 are described. Optically active 8a and 8b , obtained by chemical resolution, similarly gave the enantiomers 6a and 14a–16a of the (3aS)-series (prepared earlier from physostigmine ( 1a )) and their (3R)-enantiomers. The anticholinesterase activity of (±)- 4 , (±)- 18 , and (±)- 19 was compared with that of their optically active enantiomers.     

Total Synthesis of (±)-Patriscabrol and (±)-Boschnialactone

A total synthesis of (±)-patriscabrol (1) and (±)-boschnialactone (2) is described. The cyclopentapyranone skeleton is assembled by means of Baeyer-Villiger oxidation of ketol 5.     

Identification of 4,5-unsymmetrically substituted l-amino- and 1-(N-arylacetylamino)-1,2,3-triazoles by 13C-NMR

¹³C nmr chemical shifts are used for the structural assignment of isomeric 1-amino-1,2,3-triazoles and 1-(N-arylacetylamino)-1,2,3-triazoles unsymmetrically substituted with phenyl, methyl or hydrogen in the 4,5-positions of the triazole ring. A signal at 11 ± 0.6 ppm indicates a 4-methyl triazole derivative, whereas a signal at 7.9 ± 1 ppm indicates a 5-methyl triazole. A signal at 120 ± 0.5 ppm (C-5) indicates a hydrogen in the 5-position (unsubstituted triazole).     

Kinetics and mechanism of formation of isomeric 1-methyl- and 2-methyl-5-vinyltetrazoles

The alkylation of 5-(β-dimethylaminoethyl)tetrazole (1) with dimethyl sulfate afforded 5-(β-dimethylaminoethyl)-1-methyltetrazole (2) and 5-(β-dimethylaminoethyl)-2-methyltetrazole (3). The exhaustive alkylation of compounds 2 and 3 at the terminal dimethylamino group gave 1-methyl-(4) and 2-methyl-5-(β-trimethylammonioethyl)tetrazole (5) methyl sulfates. The proton elimination from the α-methylene (with respect to the tetrazole cycle) groups of the quaternary ammonium cations of salts 4 and 5 by the action of a base leads to the corresponding zwitterions 4 ^± and 5 ^±, which in the rate-determining step undergo the cleavage of the nitrogen—carbon bond with the formation of 1-methyl-5-vinyl- (6) and 2-methyl-5-vinyltetrazole (7). The true constant of the transformation of zwitterion 4 ^± into tetrazole 6 is 21 times higher than that for the transformation of zwitterion 5 ^± into tetrazole 7.     

The Homoconjugated Electron-Releasing Carbonyl Group of 1-Methylbicyclo[2.2.1]hept-5-en-2-one. Regioselective syntheses of 5-chloro- and 6-chloro-1-methylbicyclo[2.2.1]hept-5-en-2-one

Syntheses of (±)-2-exo-cyano-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-endo-yl acetate ( 1 ) and of (±)-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 2 ) are reported. The additon of PhSeCl to 1 afforded (±)-5-endo-chloro-2-exo-cyano-1-methyl-6-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]hept-2-endo-yl acetate ( 6 ), whereas 2 added to PhSeCl with the opposite regioselectivity giving (±)-6-endo-chloro-1-methyl-5-exo-(phenylselenenyl)-7-oxabicyclo[2.2.1]heptan-2-one ( 7 ). These adducts were converted into 5-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 9 ) and 6-chloro-1-methyl-7-oxabicyclo[2.2.1]hept-5-en-2-one ( 10 ), respectively.     

A step forward in the field of drug design: 1,5-benzothiazepines and their nucleosides

(±)cis-2-(4-methoxyphenyl)-3-hydroxy/methoxy-6-methoxy/8-methoxy-2,3-dihydro-1,5-benzothiazepin-4-[5H/5-chloroacetyl/5-(4′-methylpiperazino-1′)acetyl]-ones and nucleosides viz; (±)cis-2-(4-methoxyphenyl)-3,6-dimethoxy-2,3-dihydro-1,5-benzothiazepin-4-[5-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)]-one and (±)cis-2-(4-methoxyphenyl)-3,8-dimethoxy-2,3-dihydro-1,5-benzothiazepin-4-[5-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)]-one have been synthesized by the condensation of substituted-2-aminobenzenethiols with methyl (±)trans-3-(4-methoxyphenyl)glycidate in xylene and by stirring the 3-methoxy derivative of 1,5-benzothiazepin-4(5H)-ones with sugar namely β-D-ribofuranosyl-1-acetate-2,3,5-tribenzoate at 155–160 °C in vacuo for 10 hours, respectively. The synthesized compounds have been characterized by the elemental analyses and spectral data and screened for their antimicrobial activity.     

PbS/CdS Core–Shell Quantum Dots Suppress Charge Transfer and Enhance Triplet Transfer

A sub‐monolayer CdS shell on PbS quantum dots (QDs) enhances triplet energy transfer (TET) by suppressing competitive charge transfer from QDs to molecules. The CdS shell increases the linear photon upconversion quantum yield (QY) from 3.5 % for PbS QDs to 5.0 % for PbS/CdS QDs when functionalized with a tetracene acceptor, 5‐CT . While transient absorption spectroscopy reveals that both PbS and PbS/CdS QDs show the formation of the 5‐CT triplet (with rates of 5.91±0.60 ns⁻¹ and 1.03±0.09 ns⁻¹ respectively), ultrafast hole transfer occurs only from PbS QDs to 5‐CT . Although the CdS shell decreases the TET rate, it enhances TET efficiency from 60.3±6.1 % to 71.8±6.2 % by suppressing hole transfer. Furthermore, the CdS shell prolongs the lifetime of the 5‐CT triplet and thus enhances TET from 5‐CT to the rubrene emitter, further bolstering the upconverison QY.     

Pharmacological Effects and Pharmacokinetic Properties of a Dual-Function Peptide 5rolGLP-HV

In order to better understand the therapeutic mechanism of dual-function peptide 5rolGLP-HV in treatment of treat diabetes and its complication of thrombosis, the pharmacological effects and pharmacokinetic properties of 5rolGLP-HV were conducted in this study. 5rolGLP-HV was orally administered to diabetic mice, and the hypoglycemic mechanism was investigated. Thrombotic mice were applied to study the thrombus dissolving ability of 5rolGLP-HV. The concentration of rolGLP and rHV in rat plasma following single oral dose or intravenous injection of 5rolGLP-HV was measured. Treatment with 5rolGLP-HV decreased insulin resistance (2.96 ± 1.43 vs. 9.35 ± 1.51, p < 0.05) of diabetic mice. 5rolGLP-HV shortened the length of thrombus in thrombosis mice (2.92 ± 0.74 vs. 5.92 ± 1.16 cm, p < 0.01) and extended the thrombin time (15.35 ± 1.22 vs. 8.67 ± 0.89 s, p < 0.01) of normal mice. Meanwhile, 5rolGLP-HV restored the damage of pancreatic, liver, kidney, and adipose tissues induced in the diabetic mice. 5rolGLP-HV exhibited a fast absorption and slow elimination phase after digested into rolGLP-1 and rHV in vivo. These results suggested that 5rolGLP-HV had an ideal therapeutic potential in the prevention of β cell dysfunction in type 2 diabetes and delay of the thrombus.     

Effects of digestion,chemical separation,and deposition on Po-210 quantitative analysis

The purpose of this work was to determine polonium losses from a variety of sample types (soil, cotton fiber, and air filter) due to digestion technique, chemical separation, and deposition method for alpha energy analysis. Results demonstrated that yields from a perchloric acid wet-ash (87 ± 5 %) were similar to that from a microwave digestion (100 ± 7 %), but both were greater than the dry-ash procedure (38 ± 5 %). The polonium was separated from an SRM soil using an AG1X8 ion exchange column and deposited on a Ag disk with a recovery of 83 ± 7 % of polonium-209 (Po-209). Deposition yields without chemical separation averaged 90 ± 5 % of Po-209. The polonium-210 content was successfully measured in the three matrix types and quantitated using alpha spectroscopy.