Synthesis of Sialic Acid Analogues with the Oxime Group at C-4 Or C-5 of KDN 1

Abstract

The readily available methyl (methyl 3-deoxy-5,8:7,9-di-O-isopropylidene-β-D-glycero-D-galacto-2-nonulopyranosid)onate (7) was converted in five synthetic steps into methyl (methyl 4-acetamido-3,4-dideoxy-β-D-glycero-D-talo-2-nonulopyranosid)onate (11). Selective protection of the C-4, C-7, C-8 and C-9 hydroxy groups of methyl (methyl 3-deoxy-8,9-O-isopropylidene-β-D-glycero-D-galacto-2-nonulpyranosid)onate (2) followed by oxidation of the C-5 hydroxy group and then its oximination gave 5-hydroxyimino derivatives (15 and 16).

     

NMR studies of 4(3H)-quinazolinones and 4(3H)-quinazolinethiones

Summary Unambiguous¹H and¹³C NMR assignments for 4(3H)-quinazolinones1–6 and their corresponding 4-thiones7–12 have been made. This resulted in the revision of the previous assignments for the two benzenoid carbons (C-5 and C-8) of quinazolinones1,2,4, and5. Thionation of the nucleophilic amides1–6 has been found to cause a distinct change in the¹³C chemical shift of particularly C-4, but also of those of C-4a, C-5, and C-8a. One-bond and several long range heteronuclear coupling constants for the compounds have also been measured.

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Kernresonanzspektroskopie von 4(3H)-Chinazolinonen und 4(3H)-Chinazolinthionen

Zusammenfassung Die¹H- und¹³C-NMR-Spektren der 4(3H)-Chinazolinone1–6 und ihrer entsprechenden 4-Thione7–12 wurden zugeordnet. Dabei zeigte sich, daß eine frühere Zuordnung der beiden benzoiden Kohlenstoffe (C-5 und C-8) der Chinazolinone1,2,4 und5 falsch war. Ersatz des Sauerstoffs durch Schwefel in den nukleophilen Amiden1–6 führt insbesondere für C-4, aber auch für C-4a, C-5 und C-8a zu einer deutlichen Änderung der chemischen Verschiebung. Heteronukleare Kopplungskonstanten über eine und über mehrere Bindungen wurden bestimmt.

     

Facile synthesis and anti-proliferative activity evaluation of quinoxaline derivatives

Abstract

A series of “drug-like” compounds based on quinoxaline scaffold with arylsulfonyl hydrazinyl, arylformyl hydrazinyl or arylsulfonyl groups at C-2 and aryloxy groups at C-3, were synthesized in 4 or 5 steps involving cyclization, chlorination and coupling reactions. Cellular anti-proliferative activities of these quinoxaline derivatives in vitro were determined, which revealed that the inhibitory potency and selectivity of 6f was comparable to that of the positive control.     

Conformational Analysis of Hydroxymethyl Group of D-Mannose Derivatives Using (6S)- and (6R)-(6-2H1)-D-Mannose

ABSTRACT

D-Mannose derivatives stereospecifically deuterated at C-6 were synthesized and the unequivocal ¹H NMR assignments of H-6proS and H-6pro R were made. The preferred conformation of the hydroxymethyl groups of these compounds are discussed.     

The Role of the C-3 Substituent in the Asymmetric Dihydroxylation of Hexo-5-Enofuranosides

ABSTRACT

Asymmetric dihydroxylation of vinyl furanosides 1-6 by use of OsO₄, AD-mix-α® and β® is described yielding the corresponding hexofuranose sugars. Vinyl furanosides 2 and 3, with an ester group at C-3, and vinyl manno furanoside 5 on asymmetric dihydroxylation with AD-mix α® exhibited high R diastereoselectivity at C-5. Reversal in diastereoselectivity at C-5 was observed for the 3-deoxy vinyl furanoside 6 giving furanosaccharide 6S with the S configuration at C-5.     

Two new polyhydroxysterols produced by Fusarium solani,an endophytic fungus from Chloranthus multistachys

A highly antagonistic endophytic fungus, designated strain CL39, was originated from the leaves of Chloranthus multistachys collected in Wulong of Chongqing municipality of China in November 2015. The strain was identified as Fusarium solani based on morphological characteristics, 5.8S gene and internal transcribed spacer sequence analysis. Two new compounds, 2β, 9α-dihydroxy-5α-methoxyergosta-7, 22-diene (1), 2β, 6β-dihydroxy-5α-methoxyergosta-7, 22-diene (2) have been isolated from the culture broth of the strain. Structures of the new compounds were elucidated by detailed analysis of their spectroscopic data aided by the comparison with reported data of related derivatives, and found to belong to the polyhydroxylated steroids with a hydroxyl at C-2 instead of C-3, a rare structure among the steroids. The extract of this strain and all isolated compounds were evaluated for their antagonistic activities.     

A synthesis and biological screening of newly substituted 9-methyl-6-aryl-[1,2,4]triazolo[4,3-a][1,8]naphthyridines using chloranil

An effective, mild, and convenient method for the synthesis of 10 new substituted 9-methyl-6-aryl-[1,2,4]triazolo[4,3-a][1,8]naphthyridines (5a–j) by the oxidation of the corresponding 2-(2-ethylidenehydrazinyl)-3-aryl-1,8-naphthyridines (4a–j) using chloranil under conventional method has been described. The structures of synthesized compounds (5a–j) were established on the basis of their elemental analysis and spectral (IR, Mass, ¹³C- and¹H-NMR) data. The new compounds were synthesized with the objective of studying their antibacterial activity. The reaction will be characterized by easy workup, good efficacy, simple purification of the products, and availability of catalyst.     

5-苄氧亚氨基-5-脱氧阿维菌素B1a的合成

以阿维菌素B1a为原料经过选择性氧化合成5-氧代-5-脱氧阿维菌素B1a, 再与O-取代羟胺盐酸盐反应合成了5个5-苄氧亚氨基-5-脱氧阿维菌素B1a (4a～4e), 通过¹H NMR, ¹³C NMR, MS, IR确证了它们的结构. 生测结果表明它们对于棉铃虫和甜菜夜蛾有一定的杀虫活性.     

A new methylene bisflavan-3-ol from the branches and leaves of Potentilla fruticosa

Abstract

Dasiphora fruticosa L. (Rosaceae), also known as Potentilla fruticosa L. (syn.), is a hardy deciduous shrub widely distributed in the north temperate regions of the world. Three methylene bisflavan-3-ols (1-3), together with a procyanidin dimer, (-)-afzelechin-(4α→8)-(-)-afzelechin (4) were isolated for the first time from the branches and leaves of the titled plant, in addition to 11 known compounds (5-15). Their structures were elucidated by means of extensive spectroscopic analysis and by comparison with data reported in the literatures. Methylene 6,8-bis(7-O-glucosyl) catechin (1) was determined to be a new dimeric flavan-3-ol glycoside through a methylene linkage between C-8 and C-8 of two units. At a concentration of 128?μg/mL, the known compounds 9 – 13 exhibited antibacterial activities on Escherichia coli, Staphylococcus aureus subsp. aureus, Salmonella enterica subsp. enterica, and Pseudomonas aeruginosa. Compound 12 also showed certain glucose uptake stimulating activity.     

SnCl2/EtOH-Mediated Synthesis of Novel 4-Ethoxy- and 4-Chloroindazoles Bearing Sulfonamide Moieties

Abstract

The treatment of N-alkyl-5-nitroindazole with stannous chloride in ethanol, aftercoupling of the obtained amines with arylsulfonyl chloride in pyridine, gave the new 4-ethoxy- and 4-chloroindazoles bearing sulfonamide in moderate to good yields. Chlorination and ethoxylation of indazole were observed during the reduction of the nitro group with anhydrous SnCl₂ in ethanol. The influence of the N-alkylation in N-1 and N-2 position of 5-nitroindazole on the reduction was investigated. The presence ofethoxy group and chlorine atom at position C-4 of indazole was confirmed by x-ray diffraction analysis of compounds 7a and 8a.     

Solution and Solid State Structure of Highly Delocalised 5- Triphenylphosphoranylidenecyclopen Tene-3,4-Diones

The fully assigned ¹³C NMR spectra of the cyclic ylides 4 and 5 show that the C-1-C-2 bond is very strongly polarised consistent with substantial delocalisation of the ylide negative charge on to C-2. The X-ray structure of 5 confirms the occurrence of extensive delocalisation involving a significant contribution from up to six separate resonance forms.     

Studies on Steroids CCXXXXIV. Separation and Characterization of C-25 Epimers of Unconjugated and Conjugated Trihydroxycholestanoic Acids in Urine from a Patient with Zell Weger Syndrome by High-Performance Liquid Chromatography

Abstract

The separation and characterization of C-25 epimers of unconjugated and glycine- and taurine-conjugated 3α, 7α, 12α - trihydroxy-5β-cholestanoic acid (THCA) in biological fluids by high-performance liquid chromatography (HPLC) are described. The 5β-cholestanoic acid fraction was obtained from a urine specimen from a patient with Zellweger syndrome by passing it through a Sep-pak C₁₈ cartridge. Bile acids were derivatized quantitatively into the fluorescent compounds through the hydroxyl group at C-3 by treatment with 1-anthroyl nitrile. The derivatives were separated into the unconjugated, glycine- and taurine-conjugated fractions by ion-exchange chromatography on alipophilicgel, piperidinohydroxypropyl Sephadex LH-20. Sub-sequent resolution of each fractionin to (25s)- and (25R)-THCA was attained by HPLC on a Cosmosil 5C column. The C-25 epimers of unconjugated and conjugated Tk%A were unequivocally identified on the b asis of the irbehaviors in HPLC using mobile phases of different pHs. The ratios of the unconjugated, glycine- and taurine-conjugated (25RbTHCA to the corresponding (25S)-epimers were 16:1, 5:4 and 3:2, respectively .     

Impurities Released from Extractive Phases Used in the Analysis of Pesticides

Abstract

Elution fractions relative to solid phase extraction (SPE) procedures using C-18 bonded silica and Carbopack B columns plus C-18 membranes have been analyzed by gas chromatography-mass spectrometry (GC-MS) for the characterization of interfering compounds from the phases. Alkanes, alkenes, phthalates and some silyl compounds (silanols, siloxanes) have been tentatively identified. Experiments on commercial C-18 phases prepacked in plastic tubes show that the increased interference compared to the phases alone comes from the polymer container. N-butylbenzensulfonamide (NBBSA) was identified as causing interference when the extraction device used for SPE involved plastic components. Increasing amounts of silanol interferences released from the C-18 phases were observed after passage of the water sample, depending on the acidic pH, as evidence of the hydrolysis of the bonded silica.     

Phenolic compounds isolated from Morus nigra and their α-glucosidase inhibitory activities

Abstract

A novel benzofuranone unprecedentedly with a prenyl group at C-3, nigranol A (1), a new flavonol, nigranol B (2), and three known compounds, sanggenon M (3), nigrasin C (4), and nigrasin A (5) were isolated from the twigs of Morus nigra Linn. Their structures were elucidated on the basis of the analysis of multiple spectroscopic data. All of the compounds, along with eight previously isolated ones (6–13) were investigated for their α-glucosidase inhibitory activities. The result showed that compounds 1–13 except 4 exhibited prominent inhibitory activities against α-glucosidase. Among them, compounds 2 and 7 were the best α-glucosidase inhibitory candidates with IC₅₀ values at 1.63 and 1.43?μM, respectively. Furthermore, the structure-activity relationships of the sanggenon-type flavanones were summarized.     

Regioselective Synthesis of L-Idopyranuronic Acid Derivatives: Intermolecular Aglycon Transfer of Dithioacetal Under Standard Glycosylation Conditions

Abstract

C-1-thioacetalization of L-idofuranurono-6,3-lactone followed by regioselective p-methoxybenzylidenation at C-2 and C-4 gave the hydroxylactones 4 and 19, which were protected at C-5 with TBDMS. Lactone ring opening with methylamine followed by regioselective reductive cleavage of the 1,3-dioxane furnished acceptors 9 and 24. Intermolecular ethyl and phenyl thio group transfers were observed during the attempted preparation of disaccharide 35 through coupling reactions of either 9 or 24 with trichloroacetimidate donor 33, leading to the formation of thioglycoside of donor 33 and the thioglycoside of acceptors 9 or 24 in the furanose form. This intermolecular aglycon transfer was investigated under various glycosylation conditions. Finally, the free 4-hydroxyl groups in acceptors 9 and 24 were acetylated. Desilylation at C-5 followed by ring closure with mercuric salts afforded, in both cases, the IdopA donor and/or acceptor precursor 16.     

Synthesen von Heterocyclen, 111. Mitt.: Zur Umsetzung von Benzoylaceton und seinen Derivaten mit Malonylchlorid

Zusammenfassung Der Vorgang der thermischen Umlagerung des 4-Hydroxy-5-acetyl-6-phenyl-pyrons-(2) (1) zum 4-Hydroxy-5-benzoyl-6-methyl-pyron-(2) (4) wird an Hand weiterer Beispiele studiert und ferner der Einfluß der Substituenten am C-5 bzw. C-6 des Lactonringes untersucht.

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An investigation of more examples of the thermal rearrangement of 5-acetyl-4-hydroxy-6-phenyl-pyrone-(2) to 5-benzoyl-4-hydroxy-6-methyl-pyrone-(2) was carried out, it showed the influence of substituents at C-5 and C-6 of the lactone ring.

     

Biotransformation of (+)-isofraxinellone by Aspergillus niger and insect antifeedant activity

The biotransformation of (+)-isofraxinellone (1) by Aspergillus niger was investigated. Compound 1 was transformed to only one new compound 2. The structure of 2 was identified as (-)-(4S)-4-hydroxyisofraxinellone which was regio- and stereo-selective hydroxylated at the C-4 position by IR, EI-MS 1D and 2D NMR. Absolute configuration of hydroxyl group at the C-4 position was detected by modified Mosher’s method. Antifeedant activity of compounds 1 and 2 against larvae of Spodoptera litura was assayed. These compounds showed potent antifeedant activity and ED₅₀ (50% of effective dose) values were 3.91 and 4.43 μg/cm², respectively.     

Synthesis and characterization of some new 1,2,3-thiadiazole and 1,2,3-selenadiazole triterpene derivatives from allobetulone and 2-oxoallobetulin

Abstract

The synthesis of new 1,2,3-thiadiazole and 1,2,3-selenadiazole derivatives from triterpenoid ketones has been investigated via the corresponding semicarbazones. The intermediates 5, 8 have also been isolated, separated and their structures identified. The Hurd–Mori reaction and Lalezari method have been applied to synthesize a series of new substances 6 and 7. The regioselectivity of the functionalization mostly was centered at the C-3 position for the products 9 and 10. The structures of these compounds were confirmed by 2D-NMR spectroscopy.     

Structure of 1,5-Anhydro-D-fructose: X-ray Analysis of Crystalline Acetylated Dimeric Forms

Abstract

Acetylation of 1,5-anhydro-D-fructose under acidic conditions gave two crystalline acetylated dimeric forms, which by X-ray analysis were shown to be diastereomeric spiroketals formed between C-2 and C-2/C-3. The structures of the compounds differed only at the configuration at C-2. Acetylation or benzoylation of 1,5-anhydro-D-fructose in pyridine yielded 3,6-di-O-acetyl-1,5-anhydro-4-deoxy-D-glycero-hex-3-enos-2-ulopyra-nos or crystalline 1,5-anhydro-3,6-di-O-benzoyl-4-deoxy-D-glycero-hex-3-enos-2-ulo-pyranose.

     

Struktur- und Konfigurationsbeweis für das Diketon aus 14-Bromcodeinon

Zusammenfassung Es wird nachgewiesen, daß den aus 14-Brom-codeinon (1)^* bzw. 7-Brom-neopinon-methoperchlorat durch einfache Hydrolyse entstehenden Diketoverbindungen die Struktur und Konfiguration von ⁸⁽¹⁴⁾-7-Oxo-thebainon (5) bzw. des entsprechenden Methoperchlorats zukommt. Das durch Kondensation von5 mit o-Phenylendiamin entstehende Chinoxalinderivat7 gibt zwei am C-6a diastereomere Dihydroverbindungen (8 und10), wobei8 das Enantiomere des Kondensationsproduktes von Sinomeninon (6) und o-Phenylendiamin darstellt.

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Proof of structure and configuration of the diketone derived from 14-bromo-codeinone

The diketo compounds formed in the hydrolysis of 14-bromocodeinone (1) and 7-bromoneopinone methoperchlorate, resp., have been shown to possess structure and configuration of ⁸⁽¹⁴⁾-7-oxothebainone (5) and its methoperchlorate, resp. The quinoxaline derivative7, obtained by condensation of5 with o-phenylenediamine, yields two dihydro compounds (8 and10) diastereomeric at C-6a.8 has been found to be the enantiomer of the condensation product obtained from sinomeninone (6) and o-phenylenediamine.

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Teile aus der Dissertation Univ. Wien 1960.