Ein neuer Reaktionsweg zu 1, 3-Dicarbonylderivaten. Modelluntersuchungen am A/B-Teil von 3-Oxo-5α-steroiden

A New Route to 1, 3-Dicarbonyl Derivatives, Model Investigations on the A/B-Part of-3-Oxo-5α-steroids Starting from 1 the 1, 3-dicarbonyl compounds 4a – d were synthetized via the enynes 2a – e and the relatively unstable epoxides 3a – d . The latter were reacted with 95% formic acid to gave 4a – d ; small amounts of the furane derivatives 5a – c were identified as by-products in this last step. In the presence of catalytic amounts of HgSO₄ the epoxides 3a – c yielded with 95% formic acid the furanes 5a – c , but no detectable amounts of 4a – c .     

Selectively C‐Deuterated Indigotins

Selectively C‐deuterated indigotins were synthesized from halogenated indigotins 1a – c as precursors. The described reactions – used already by the ancient purple dyers – allowed the introduction of D‐atoms at defined positions of the indigo molecule. The exchange of halogen atoms by D‐atoms was induced by UV irradiation of the leuco compounds 2a – c and 3a – c in D₂O. The resulting leuco forms 4a – c were oxidized to the deuterated indigotins 5a – c . Some conclusions were drawn as to the kinetics of the reaction. The physical properties of the new compounds were determined.     

4‐Substituted 2,3‐Dihydroisoxazoles as Masked Azomethine Ylides: Access to Pyrrole Derivatives by 1,5‐ and 1,7‐Dipolar Electrocyclizations of Enynyl Derivatives

The enynyl‐substituted 2,3‐dihydroisoxazoles (‘isoxazolines') 9 – 14 were prepared by highly (Z)‐selective Peterson olefination reaction from the corresponding carbaldehydes 6 – 8 . On short‐time thermolysis (280 – 406°/10 s) the TMS derivatives 9 – 11 give rise to the annulated pyrrolines 18 – 20 , which, in some cases, suffer CH₄ elimination affording the pyrroles 15 – 17 . In contrast, thermolysis of the terminal alkyne derivatives 12 – 14 leads to the bicyclic compounds 21 – 23 . The reaction pathways are discussed on the basis of the formation of conjugated azomethine ylides as key intermediates, which either undergo a 1,5‐cyclization to 18 – 20 or a 1,7‐ring‐closure affording cycloallene intermediates of type V , which are further transformed into the azepino pyrroles 21 – 23 .     

Synthesis of Thiazole and Fused Thiazolo Derivatives

The syntheses of thiazole and fused thiazolo derivatives 2 – 4 , 6 – 8 , 10a – 11b , 13 – 16 from heterocylic isothiocyanates 1 , 5 , 9 , and 12 bearing an ortho ester group and bifunctional reagents, such as substituted propargylamines, is described. Different regioselectivity of intramolecular nucleophilic attack of the thiourea S-atom on the C ? C bond, resulting in the formation of both thiazolo and thiazino derivatives, as well as NMR structure elucidation are discussed.     

pH‐Independent Recognition of the dG ⋅ dC Base Pair in Triplex DNA: 9‐Deazaguanine N7‐(2′‐Deoxyribonucleoside) and Halogenated Derivatives Replacing Protonated dC

Triplex-forming oligonucleotides (TFOs) containing 9-deazaguanine N⁷-(2′-deoxyribonucleoside) 1a and halogenated derivatives 1b,c were synthesized employing solid-phase oligonucleotide synthesis. For that purpose, the phosphoramidite building blocks 5a – c and 8a – c were synthesized. Multiple incorporations of 1a – c in place of dC were performed within TFOs, which involved the sequence of five consecutive 1a – c ⋅ dG ⋅ dC triplets as well as of three alternating 1a – c ⋅ dG ⋅ dC and dT ⋅ dA ⋅ dT triplets. These TFOs were designed to bind in a parallel orientation to the target duplex. Triplex forming properties of these oligonucleotides containing 1a – c in the presence of Na⁺ and Mg²⁺ were studied by UV/melting-curve analysis and confirmed by circular-dichroism (CD) spectroscopy. The oligonucleotides containing 1a in the place of dC formed stable triplexes at physiological pH in the case of sequence of five consecutive 1a ⋅ dG ⋅ dC triplets as well as three alternating 1a – c ⋅ dG ⋅ dC and dT ⋅ dA ⋅ dT triplets. The replacement of 1a by 9-halogenated derivatives 1b,c further enhanced the stability of DNA triplexes. Nucleosides 1a – c also stabilized duplex DNA.     

The unusual fragmentation of long‐chain feruloyl esters under negative ion electrospray conditions

Long‐chain ferulic acid esters, such as eicosyl ferulate ( 1 ), show a complex and analytically valuable fragmentation behavior under negative ion electrospay collision‐induced dissociation ((?)‐ESI‐CID) mass spectrometry, as studied by use of a high‐resolution (Orbitrap) mass spectrometer. In a strong contrast to the very simple fragmentation of the [M + H]⁺ ion, which is discussed briefly, the deprotonated molecule, [M – H]^?, exhibits a rich secondary fragmentation chemistry. It first loses a methyl radical (MS²) and the ortho‐quinoid [M – H – Me]^‐? radical anion thus formed then dissociates by loss of an extended series of neutral radicals, C_nH_2n + 1^? (n = 0–16) from the long alkyl chain, in competition with the expulsion of CO and CO₂ (MS³). The further fragmentation (MS⁴) of the [M – H – Me – C₃H₇]^? ion, discussed as an example, and the highly specific losses of alkyl radicals from the [M – H – Me – CO]^‐? and [M – H – Me – CO₂]^‐? ions provide some mechanistic and structural insights.     

Synthesis of Novel 4‐Substituted Coumarins,Docking Studies,and DHODH Inhibitory Activity

Coumarins are the important class of naturally occurring heterocyclic compounds. Activities like antioxidant, antibacterial, anti‐inflammatory, and anticancer have been reported for coumarin derivatives. Present work details the synthesis of substituted coumarin‐4‐pyrrolones as well as coumarin‐4‐acetyl amino acids and their DHODH inhibitory activity, which is a dual target for malaria and cancer. Coumarin‐4‐acetic acids ( 2a – c ) were coupled with different methyl esters of α‐amino acids ( 3 ) giving rise to corresponding coumarin‐4‐acetyl amino acid methyl esters ( 4a – o ), which on hydrolysis under basic condition underwent cyclization forming substituted dihydropyrrole‐2‐ones ( 5a – i ), dihydroindolizine‐3‐ones ( 5j – l ), and dihydropyrrolizin‐3‐one ( 5m – o ). Acidic hydrolysis of the compounds ( 4a – o ) yielded corresponding coumarin‐4‐acetyl amino acids ( 6a – f ). The docking study was performed with the protein 4IGH (obtained from PDB) using Surflex–Dock module. The newly synthesized compounds were tested for DHODH inhibitory activity using Brequinar as the standard. Compound 6b showed remarkable inhibition compared with the standard, and the other compounds with terminal COOH showed moderate inhibition.     

Selective Synthesis of [2＋2] Macrocyclic Schiff Bases from Chiral 1,4-Diamines

[2＋2] macrocyclic Schiff bases of three kinds have been synthesized from chiral 1,4-diamines by use of different methods. Macrocyclic Schiff bases 1a-1c have been selectively obtained based on a non-templated dilution method from chiral 1,4-diamines a-c and dialdehyde DA1, whereas macrocycles 2a-2c have been selectively produced from reaction of diamines a-c and dialdehyde DA2 in the presence of boric acid as templates. Macrocyclic Schiff bases 3a-3c have been afforded in high selectivity from diamines a-c and dialdehyde DA3 by means of sodium-template. All the titled compounds have been confirmed by ^1H NMR and ESI-MS analyses.     

Mononuclear Tetraamineplatinum(II) Complexes: Synthesis,Anticancer Activity,DNA Binding,and Cellular Uptake

The synthesis of three bis[(tert‐butoxy)carbonyl]‐protected (tetramine)dichloroplatinum complexes 2a – c of formula cis‐[PtCl₂(LL)] and of their cationic deprotected analogs 3a – c and their evaluation with respect to in vitro cytotoxicity, intramolecular stability, DNA binding, and cellular uptake is reported. The synthesis comprises the complexation of K₂[PtCl₄] with di‐N‐protected tetramines 1a – c to give 2a – c and subsequent acidolysis, yielding 3a – c . The cytotoxicity of the complexes is in direct relation to the length of the polyamine. Complexes 3a – c display a significant higher affinity for CT DNA as well as for cellular DNA in A2780 cells than cisplatin.     

Combining spiro-fused cyclohexadienone – tetrahydrofuran ring system with glycine: Asymmetric synthesis of a new class of α-amino acid derivatives

Herein, we present the asymmetric synthesis of spiro-fused cyclohexadienone – tetrahydrofuran-embedded glycine derivatives as a new class of nonproteinogenic α-amino acid derivatives. Starting from commercially available 2-allylphenols, key β-hydroxy-α-amino esters were synthesized via high-yielding multi-step reaction sequences involving Sharpless asymmetric dihydroxylation as the chirality induction step. PhI(OAc)₂-mediated oxidative dearomatization – spirocyclization of phenol-tethered β-hydroxy-α-amino esters efficiently produced the corresponding spiro-fused cyclohexadienone – tetrahydrofuran-embedded glycine derivatives, providing a general route to this hitherto-unreported class of compounds that are equipped with three privileged scaffolds (cyclohexadienone – tetrahydrofuran – α-amino ester).     

A Simple Procedure for the Preparation of Chiral ‘Tris(hydroxymethyl)methane’ Derivatives

The aldol adducts 1a – 13a of R,R-2(tertbutyl)-6-methyl-1,3-dioxan-4-one (from 3-hydroxybutanoic acid) to aldehydes, single diastereoisomers obtained as described previously, are acetylated or benzoylated to the corresponding esters 1b – 5b and 6c – 13c , respectively, which in turn are reduced with LiAlH₄ to the title compounds 14 – 24 . The enantiomerically pure triols thus available may be useful as chiral building blocks, as auxiliaries for enantioselective reactions, and as center pieces for chiral dendrimers.     

The chemistry and physics of zinc oxide surfaces

Metal oxides are virtually everywhere – only gold has the property not to form an oxide on its surface when exposed to the ambient. As a result, understanding the physics and chemistry of oxide surfaces is a topic of pronounced general interest and, of course, also a necessary prerequisite for many technical applications. The most important of these is certainly heterogeneous catalysis, but one has to realize that – under ambient conditions – virtually all phenomena occurring at liquid/metal and gas/metal interfaces are determined by the corresponding oxide. This applies in particular to friction phenomena, adhesion and corrosion. A necessary – but not necessarily sufficient – condition for unravelling the fundamentals governing this complex field is to analyze in some detail elementary chemical and physical processes at oxide surfaces. Although the Surface Science of metal surfaces has seen a major progress in the past decades, for oxides detailed experimental investigations for well-defined single crystal surfaces still represent a formidable challenge – mostly because of technical difficulties (charging), but to some extent also due to fundamental problems related to the stabilization of polar surfaces. As a result, the amount of information available for this class of materials is – compared to that at hand for metals – clearly not satisfactory. A particular disturbing lack of information is that about the presence of hydrogen at oxide surfaces – either as hydroxy-species or in form of metal hydrides.In the present review we will summarize recent experimental and theoretical information which has become available from single crystal studies on ZnO surfaces. While the number of papers dealing with another oxide, rutile TiO₂, is significantly larger (although titania does not exhibit a polar surface), also for zinc oxide a basis of experimental and theoretical knowledge as been accumulated, which – at least for the non-polar surfaces – allows to understand physico-chemical processes on an atomic level for an increasing number of cases. In particular with regards to the interaction with hydrogen a number of – often surprising – observations have been reported recently. Some of them carry implications for the behaviour of hydrogen on oxide surfaces in general. We will present the currently available information for both, experiment and theory, and demonstrate the rather large variety of this material’s surface properties.     

Synthesis and Application of Some Azo and Azomethine Dyes Containing Pyrazolone Moiety

3-Amino-1-phenyl-4,5-dihydro-1H-pyrazol-5-one (1) was used as starting material for the synthesis of a number of azo compounds 3a—3c and azomethine derivative 4. The deblocking of 3a—3c and 4 gave rise to 5a—5c and 6 in which a free amino was revealed. The diazonium salts of 5a—5c and 6 were coupled with several phenols to produce a number of bis azo compounds 7a—7c and 8a—8c with azomethine in position 4 and azoic group in position 3. The prepared dyes were structurally confirmed by elemental analysis, spectral methods and applied to different fibers (wool, polyester and blend of wool/polyester) as disperse dyes and their fastness properties were measured.     

Estimation of betulinic acid from wild fruit extracts of Ziziphus mauritiana and Ziziphus nummularia from different regions of North India by a validated high-performance thin-layer chromatography method

JPC – Journal of Planar Chromatography – Modern TLC - The Ziziphus fruits are recognized as a rich source of biologically active compounds, such as polysaccharides, phenolics,...     

A Validated Stability-Indicating HPTLC Method for the Estimation of Gemcitabine HCI in its Dosage Form

JPC – Journal of Planar Chromatography – Modern TLC - Gemcitabine belongs to a class of drugs known as antimetabolites (pyrimidine analog) used in various carcinomas, such as pancreatic...     

β-Cleavage of Bis(homoallylic) Potassium Alkoxides. Preparation of 3-Hydroxypropyl and 4-Hydroxybutyl Propenyl Ketones from γ- and δ-Lactones. Synthesis of (±)-Rose oxide

Starting from γ- and δ-lactones 1 – 3 , a two-step preparation of 3-hydroxypropyl and 4- hydroxybutyl propenyl ketones 10 – 18 is described, involving as the key step the β-cleavage of the bis(homoallylic) potassium alkoxides 4a – 9a . The novel methodology is illustrated by a short synthesis of (±)-rose oxide( 20 ).     

Mass spectrometry of 3-substituted 4-hydroxyisoquinolines and their derivatives

Under electron impact, 3-aryl-4-hydroxyisoquinolines form [M – H]⁺, [M – CO]⁺ and [M – H – CO]⁺ ions with a subsequent elimination of HCN or CH₃CN. A cyclic structure for the [M – H]⁺ ion is suggested. The primary act of fragmentation of the corresponding methyle ether derivatives is the loss of CH₃?, as well as H?; the further fragmentatio is similar to that described above. It has been established that the unusual [M – H]⁺, [M – OH]⁺ and [M – CH₅?]⁺ ions are formed when 8 fragments. Fragmentation schemes for all compounds are proposed based upon high resolution mass spectra and deuterated analogues.     

Bioanalysis of Naproxen by High Performance Reversed Phase Liquid Chromatography with Photometric and Fluorimetric Detection

Abstract

Methods for the quantitative determination of NAPROXEN and its main metabolite in plasma and urine are described. The separation is based on reversed phase liquid chromatography with LiChrosorb RP 8 (5 μm) as the support and methanol/phosphate buffer pH 7 as mobile phase, in some cases with addition of tetrabutyl ammonium ion as ion-pairing agent to improve the chromatographic selectivity. With UV-detector and a simple filter fluorometer an extraction-evaporation procedure is used for both plasma and urine determinations, while the high selectivity and sensitivity of a sophisticated fluorescence detector permits the direct injection of diluted samples on to the column. Use of an internal standard improves the within-run precision (s_rel%), which for plasma determinations of NAPROXEN are - with UV-detection, 0.2 – 1.7% (range 10 – 40 μg/ml), with filter fluorometer, 2.4 – 5.9% (range 12 – 58 μg/ml), and with fluorescence detector, 0.8 – 4.1% (range 5 – 20 μg/ml).