Quantitative determination of amoxicillin and its decomposition products by high-performance liquid chromatography

Amoxicillin, amoxicilloates, amoxicillin oligomers and amoxicillin piperazine-2,5-dione are separated by reversed-phase (C8) high-performance liquid chromatography with gradient elution. Quantitative results are reported for a number of samples. Amoxicillin trihydrate samples mostly contain amoxicilloate as the main impurity. Samples of the sodium salt also contain the piperazine-2,5-dione and the dimer. Higher oligomers such as the trimer and tetramer were not present in significant amounts. Several samples were also analysed by a mercurimetric titration method.     

A novel rearrangement in electrospray ionization multistage tandem mass spectrometry of amino acid ester cyclohexyl phosphoramidates of AZT

Several amino acid ester cyclohexyl phosphoramidates of AZT as anti-HIV prodrugs were synthesized and investigated by electrospray ionization tandem mass spectrometry (ESI-MS(n)). A novel methoxy group migration from the carbonyl group to the phosphoryl group was observed in ESI-MS2. This migration is believed to be a general pathway for ions with a methyl ester moiety at the gamma-position to a phosphoric acid moiety, which is assisted with metal ions such as Li(+), Na(+) and K(+). Coordination between metal ions with both the carbonyl oxygen and phosphoryl oxygen might be a key factor responsible for this migration.     

Rigid Scaffolds: Synthesis of 2,6-Bridged Piperazines with Functional Groups in all three Bridges

The activity of pharmacologically active compounds can be increased by presenting a drug in a defined conformation, which fits exactly into the binding pocket of its target. Herein, the piperazine scaffold was conformationally restricted by substituted C₂- or C₃-bridges across the 2- and 6-position. At first, a three-step, one-pot procedure was developed to obtain reproducibly piperazine-2,6-diones with various substituents at the N-atoms in high yields. Three strategies for bridging of piperazine-2,6-diones were pursued: 1. The bicyclic mixed ketals 8-benzyl-6-ethoxy-3-(4-methoxybenzyl)-6-(trimethylsilyloxy)-3,8-diazabicyclo[3.2.1]octane-2,4-diones were prepared by Dieckmann analogous cyclization of 2-(3,5-dioxopiperazin-2-yl)acetates. 2. Stepwise allylation, hydroboration and oxidation of piperazine-2,6-diones led to 3-(3,5-dioxopiperazin-2-yl)propionaldehydes. Whereas reaction of such an aldehyde with base provided the bicyclic alcohol 9-benzyl-6-hydroxy-3-(4-methoxybenzyl)-3,9-diazabicyclo[3.3.1]nonane-2,4-dione in only 10 % yield, the corresponding sulfinylimines reacted with base to give N-(2,4-dioxo-3,9-diazabicyclo[3.3.1]nonan-6-yl)-2-methylpropane-2-sulfinamides in >66 % yield. 3. Transformation of a piperazine-2,6-dione with 1,4-dibromobut-2-ene and 3-halo-2-halomethylprop-1-enes provided 3,8-diazabicyclo[3.2.1]octane-2,4-dione and 3,9-diazabicyclo[3.3.1]nonane-2,4-dione with a vinyl group at the C₂- or a methylene group at the C₃-bridge, respectively. Since bridging via sulfinylimines and the one-pot bridging with 3-bromo-2-bromomethylprop-1-ene gave promising yields, these strategies will be exploited for the synthesis of novel receptor ligands bearing various substituents in a defined orientation at the carbon bridge     

THE PHOTOCHEMISTRY OF PIPERAZINE-2,5-DIONE IN AQUEOUS SOLUTION

Abstract The aqueous photochemistry of deoxygenated solutions of piperazine-2,5-dione was investigated and three products were isolated in low yield using preparative high-performance liquid chromatography: 3,3'-bis(piperazine-2,5-dione) ( 1 ), oxamide and N-methyloxamide. The structure of 1 was established by infrared, mass and high-field proton magnetic resonance spectroscopy, and by the synthesis of its meso diastereoisomer. A 1:2 mixture of meso and racemic diastereoisomers of 1 was formed in good yield in thermally or photochemically initiated reactions of piperazine-2,5-dione with t -butyl peroxide in aqueous t -butanol.
The rate of photolysis of aqueous piperazine-2,5-dione was markedly enhanced in the presence of iron(II) ions, copper(II) ions or powdered titanium dioxide. A diastereomeric mixture of 1, oxamide and N-methyloxamide were isolated from the reaction with iron(II) ions. The possibility that oxamides were formed in these reactions via reaction with atmospheric oxygen was eliminated in a series of control experiments.
The results suggest α-carbon radicals are important in the photolysis of peptides in fluid aqueous media, possibly as a consequence of photoinduced electron transfer. No significant adduct formation could be detected when mixtures of piperazine-2,5-dione and uracil or thymine were irradiated in frozen aqueous solution.     

A new method for the preparation of 2-thio substituted furans by methylsulfanylation of gamma-dithiane carbonyl compounds

Several related methods for the preparation of differentially substituted 2-thiofurans are described. The general procedure involves the formation of a thionium ion from a gamma-dithianyl substituted carbonyl compound followed by cyclization of this reactive intermediate onto the tethered carbonyl group. Two methods for thionium ion generation were explored. One of these involved an acid-catalyzed reaction of beta-ketenedithioacetals, prepared from the condensation of 2,2-bis(methylsulfanyl)acetaldehyde with a variety of ketones. Cyclization followed by loss of methane thiol gave 2-thiofurans 17, 18 and 23, 24 in 70-90% yield. Attempts to prepare 5-heteroatom substituted 2-thiofurans from the corresponding beta-ketenedithioacetal amides or esters were unsuccessful, leading to 1,2-thio rearranged products. A more successful route involved the reaction of beta-acetoxy-gamma-thianyl carbonyl compounds with dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF). Treatment of the dithiane with this reagent resulted in the smooth generation of a thionium ion. Cyclization followed by loss of acetic acid afforded thiofurans 17, 18, 23, 47-49, 51, and 61-64 in 40-100% yield. The N-butenyl substituted thioamido furan furnished a rearranged hexahydropyrroloquinolin-2-one in high yield when heated at 110 degrees C.     

C-13 magnetic resonance studies of some papaveraceae alkaloids

The natural abundance ¹³C magnetic resonance spectra of some Papaveraceae alkaloids have been determined at 22·628 MHz employing the pulse Fourier transform technique. Several techniques were employed to aid in spectral assignments and it has been possible to make self-consistent assignments for all the resonances for these alkaloids. Evidence is presented for trans-annular interaction between the amino group and the carbonyl group situated across the ten-membered ring.     

A facile synthesis of potassium selenocarboxylates and their oxidation with XeF2 to diacyl diselenides: An X‐ray structural analysis of di(4‐methoxybenzoyl) diselenide

Several potassium selenocarboxylates were synthesized in moderate to good yields by the direct reaction of acyl chlorides with potassium selenide. The potassium salts were readily oxidized with XeF₂ to give diacyl diselenides in quantitative yields. The structure of di(4‐methoxybenzoyl) diselenide was established by X‐ray diffraction analysis. Intramolecular interactions between the carbonyl oxygen and the selenium that is connected to the opposite carbonyl group were observed. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 373–379, 1999     

Liquid-Crystalline Properties of Unsaturated Piperazine-2,5-dione Derivatives

The synthesis, characterization, and mesomorphic properties of a new type of liquid-crystalline compounds, (3Z,6Z)-3,6-bis(3,4-dialkoxybenzylidene)piperazine-2,5-diones are reported. These compounds were derived from unsaturated piperazine-2,5-dione as the core group, and were prepared by condensation reactions of 1,4-diacetylpiperazine-2,5-dione and 3,4-dialkoxybenzaldehydes. The products were characterized by ¹H- and ¹³C-NMR spectroscopy, and elemental analysis, and the phase behavior of these compounds was characterized and studied by differential scanning calorimetry (DSC) and polarization microscopy. The results indicate that these rod-like compounds exhibit smectic C (S_c) phases. However, for the derivatives with two flexible alkoxy side chains, highly ordered smectic G (S_G) phases were also formed and confirmed by X-ray powder diffraction. The liquid crystallinity of these molecules was attributed to the presence of intermolecular hydrogen bonds involving the NH groups of the heterocyclic rings. The correlation of phase behavior and molecular shape is also discussed.     

Highly diastereoselective desymmetrizations of cyclo(Pro,Pro): an enantioselective strategy toward phakellstatin and phakellin

[reaction: see text] Monoenolates of C(2)-symmetric, proline-derived piperazine-2,5-diones were generated and trapped with a variety of electrophiles to produce, in a highly diastereoselective fashion, functionalized diketopiperazines (DKPs). These reactions provide the basis for an asymmetric, desymmetrization strategy toward the marine alkaloids phakellstatin and phakellin. The relative stereochemistry of the functionalized DKPs was confirmed by single-crystal X-ray analysis and/or NOE experiments. Bis-functionalization of the DKPs was also found to proceed with high levels of diastereoselectivity.     

Zn对非晶态Co-B催化剂巴豆醛选择加氢性能的影响

考察了Zn的两种不同修饰方式对非晶态Co-B催化剂上巴豆醛液相加氢性能的影响, 并采用ICP, XRD, DSC, XPS等手段对催化剂进行了系统的表征. 实验表明, 当反应液中加入适量的ZnCl₂时, Zn^2＋离子一方面通过在活性位上的选择性吸附抑制C＝C键的加氢; 另一方面, Zn^2＋离子可通过极化作用使羰基活化, 令解离吸附氢对羰基的亲电进攻更容易, 从而提高羰基的加氢活性. 当ZnCl₂/Co摩尔比为5%时, 羰基加氢产物巴豆醇的最高得率为36 mol%, 达到文献较高水平. 催化剂制备时加入的ZnCl₂在催化剂中以Zn(OH)₂的形式存在, 并使催化剂中的Co, B氧化物增多. 这些氧化物无选择性地覆盖了活性位, 使羰基和C＝C键的加氢速率以相似的程度下降, 这样不仅不能有效提高巴豆醇的选择性, 还使催化剂活性急剧降低.     

Mass spectrometry of 2-arylaziridin-2-ylphosphonates

The mass spectral fragmentations of 2-arylaziridin-2-ylphosphonates having a carbonyl function at C(3) were studied. Cleavage of either a carbonyl group or PO(OR)₂ from the molecular ion is the primary pathway.     

SYNTHESIS AND FREE RADICAL POLYMERIZATION OF 2-OXO-3-METHYLEN E-5-PHENYL-1,4-DIOXAN

The novel cyclic monomer, 2-oxo-3-methylene-5-phenyl-1,4-dioxan, was synthesized by a set of reactions. Several intermediates were prepared and characterized in order to determine the monomer structure. The presence of chiral centers in the intermediates and resulting monomer makes it complicated to separate , purify and characterize them. It is a very reactive monomer which will polymerize even at room temperature if expose to moisture and air. This monomer can undergo essentially quantitative flee radical ring opening polymerization. The driving force for ring opening is the formation of new carbonyl group and benzylic radical. The monomer and polymer structure were established by IR, ~1H NMR, ~(13)C NMR and elemental analysis or high resolution mass spectrum. The molecular weight of the resulting polymer was estimated by viscosity determination.     

1,6-六亚甲基二异氰酸酯自聚产物的结构表征

用IR与NMR表征了用醋酸钾为催化剂时 1,6 六亚甲基二异氰酸酯 (HDI)自聚产物的结构 .结果表明 ,自聚主产物是三聚体异氰脲酸酯 ,主要含有三聚体异氰脲基、异氰酸根 ,同时含有由杂质带来的微量氨基甲酸酯、脲基甲酸酯基、取代脲基、缩二脲基 .一维核磁谱及二维化学位移相关谱分辨出 7种羰基 ,一种NCO基 ,确定了氮上 8种不同取代结构的分子链连接情况 .通过建立理论模型 ,定量地描述了自聚产物的结构 .     

The crystal structure and conformation of N-[2,2-dimethyl-3-(2-methylpropenyl)- cyclopropylcarbonyl]-5-methylisoxazolin-3-one

The title compound has been synthesized and its crystal structure was determined by X-ray crystallographic method. The crystal is triclinic, space group P-1, with unit cell dimensions a = 6.146 (5), b = 8.473(6), c = 14.383(5) Å; α = 77.47 (4), β = 82.84 (4), γ = 69.00 (8)° and Z = 2. The results obtained reveal that the molecule of the title compound keeps a long conjugative system involving CC double bond, cyclopropane ring, carbonyl group and isoxazolinone ring and adopts a low energy conformation including s-trans of CC double bond, s-cis of carbonyl group with respect to the three-membered ring and like-s-trans of carbonyl group with the carbonyl group within the heterocyclic moiety.     

Hydrogen bonding structure and stability of alpha-chitin studied by 13C solid-state NMR

The structure and stability of hydrogen bonds in alpha-chitin were investigated by (13)C solid-state NMR measurements at different temperatures. Splitting of the carbonyl carbon signal for alpha-chitin was interpreted as two types of hydrogen bonding; the peaks at 173.5 and 175.8 ppm were assigned, respectively, to a carbonyl carbon hydrogen bonded exclusively to the NH group and a carbonyl carbon hydrogen-bonded to both NH and C(6)-OH groups. Approximately 60% of carbonyl groups exclusively contributed to the intermolecular hydrogen bonding and ca. 40% of them to the combination of intermolecular and intramolecular hydrogen bonding. Internal rotation around the C(5)-C(6) bond was detected at 55 degrees C.     

13C NMR spectroscopic studies of the behaviors of carbonyl compounds in various solutions

¹³C NMR spectroscopic studies were performed for carbonyl compounds having a hydroxyl group, a carboalkoxy group, an acetoxy group, or a carboxyl group in various solvents with different polarities for observation of their behaviors of ¹³C NMR chemical shifts of carbonyl carbons in solutions. It was found that the chemical shifts of the carbonyl carbons in ¹³C NMR have good correlation with the empirical parameter for solvent polarities, E_T^N, depending on the structures. Inter- or intramolecular hydrogen bonding and dipolar-dipolar interactions appear to play a key role in this observation.     

The synthetic versatility of alkoxycarbonyl- and hydroxymethyl-piperazine-2,5-diones

Alkoxycarbonylpiperazine-2,5-diones are versatile precursors for the α-functionalisation of piperazine-2,5-diones. The alkoxycarbonyl group activates the α-carbon position to alkylation reactions and this provides a mild and selective method for the extension of the carbon framework of piperazine-2,5-diones. In addition, the alkoxycarbonyl group can be converted to the carboxy group, which in turn can be ‘deleted’ or manipulated for the installation of carbon and/or heteroatom substituents where desired, the latter via N-acyliminium chemistry. We also demonstrate that hydroxymethylpiperazine-2,5-diones complement carboxypiperazinediones as precursors for the generation of N-acyliminium ions.     

Identification of amino acid phosphorodiamidates of antiviral nucleosides using electrospray ionization tandem mass spectrometry

Several amino acid phosphorodiamidate derivatives of d4T as anti-HIV prodrugs were synthesized and investigated using electrospray ionization multistage tandem mass spectrometry (ESI-MS(n)). A novel methyl group migration in gas phase was observed in ESI-MS(2) of the sodium adducts of amino acid methyl ester of phosphorodiamidates of 2',3'-didehydro-2',3'-dideoxythymidine (d4T). The proposed structures of the rearrangement ions were confirmed by high resolution tandem mass spectrometry. A possible mechanism involving the pentacoordinate phosphoric-carboxylic phosphate anhydride was proposed, in which a seven-membered ring intermediate was formed by coordination with the metal ion between the phosphoryl group and carbonyl oxygen atom. Thus, the intrinsic properties of phosphoryl group might be the key factors responsible for this migration.     

Incipient Nucleophilic Attack on a Carbonyl Group Adjacent to a Stereogenic Centre in Peri Naphthalene Derivatives

The crystal structures of four peri-naphthalene derivatives model the Felkin–Anh approach of a nucleophilic centre (OH or NMe₂) to a carbonyl group attached to a stereogenic centre bearing a large (phenyl), medium (methyl) and a small (hydrogen) group. Thus, the conformation about the (O=)C−C* bond directs the phenyl group approximately perpendicular to the carbonyl group and away from the nucleophile, whose line of approach lies close to the hydrogen atom attached to the stereogenic centre. The nucleophile approaches the carbonyl group at 102.99(11)-112.34(9)° (for NMe₂) and at 118.56(14)° (for OH). The small pyramidalization of the carbonyl carbon towards the nucleophile increases as the nucleophilic centre approaches closer.     

Cascade Reaction to Selectively Synthesize Multifunctional Indole Derivatives by IrIII-Catalyzed C−H Activation

An effective and condition-controlled way to synthesize with high selectivity a variety of functionalized indoles with potent biological properties has been developed. Notably, 2,4-dialkynyl indole products were obtained by direct double C−H bond alkynylation, whereas alkynyl at the C4 position could convert to carbonyl to generate 2-alkynyl-3,4-diacetyl indoles fast and effectively. Additionally, a one-pot relay catalytic reaction led to 2,5-di-alkynyl-3,4-diacetyl indoles when using a carbonyl group as the directing group and by controlling the type and quantity of additives. A possible mechanism was proposed based on many studies including deuterium-exchange experiments, the necessary conditions of product conversion, and the effect of water on the reaction.