A New Class of Nucleoside Analogues. Synthesis of N. -Pyrimidinyl-and N9-Purinyl-4′-hydrqxy-3-(Hydsoxymethyl)butanes1 # 2

Interest in non-glycosidic derivatives of the nucleo-bases uracil, theymine, cytosine, adenine and guanine stems from their status as nucleoside analogues. It is noteworty in this connection that the anti-biotics aristeromycin³ and eritadenine⁴ consist of an adenine moiety linked, via N₉ -, to a cyclopentyl or a butiric acid derivative, respectively, in place of the conventional nucleoside sugars. A non-glycoaidic 5-fluorouracil derivative⁵ has been recently reported to be clinically effective in the treatment of Gastrointestinal cancer. In this communication the ficile synthesis of 4-hydroxy-3-(hydroxymethyl)butyl derivatives of the nucleobases (1) is described. These nucleoside analogues are characterized by the special feature that they incorporate two hydroxyl functions in a relationship corresponding to the 3′-and 5′-hydroxy groups of the 2-deodyribose Doiety. Phosphorylationj of the hydroxyl groups or their linkage via phosphodiester of the hydroxyl groups or their linkage via phosphodiester bridges should give nucleotide analogues or novel nucleic acid models. The latter molecular systems constitute a new class of potential anti-mitotic or anti-viral agents. One principle synthetic approach to compounds of general structure 1 was visualized via the intermediacy of 2-(hydroxymethyl) - 4-aminobutanol (2, ReH) which, acting as a common precursor, could be elaborated to the desired pyrimidine or purine derivative, via its amine function. The synthesis of amine 2 was achieved according to the reaction sequence described in Scheme I. Diethyl malonate was coupled with 2,2-dimethoxybromoethane, in presence of sodium ethoxide (EthoH, 170°, autoclave). The resulting diester (3) was reduced with LialH₄ to the corresponding diol (4), which was benzylated (NaH, C₆H₅CH₂Cl) to 5. When 5 was refluxed with NH₂OH.HCl in methanol for 30 min., a mixture of oximes 6a,b (syn- and anti-) and nitrile 7 was isolated. The latter mixture could be directly reduced with LiAlH₄ to amine 2,⁶ in high yield.     

Usefulness of field desorption mass spectrometry in determining molecular masses of carotenoids,natural carotenoid derivatives and their chemical derivatives

Field desorption (FD) mass spectrometry was applied to the determination of the molecular masses of carotenoids, natural carotenoid derivatives and their chemical derivatives. All the carotenoids examined gave the molecular ion as the base peak with negligible fragment ions. Carotenoid glucoside and its fatty acid monoester were successfully determined without acetylation, whereas carotenoic acids (carboxylate and sulphate) needed to be converted into methyl esters prior to analysis. The applicable ranges of molecular masses and polarity were very wide. In addition, carotenoid glycoside gave only [M]⁺˙ without [M + H]⁺˙ and [M + cation]⁺˙. The numbers of carbonyl groups, primary and/or secondary hydroxyl groups and total hydroxyl groups could be directly determined according to the increase in mass units of the carotenoids after chemical reduction, acetylation and trimethylsilylation, respectively. Owing to the negligible fragment ions, FD analysis was also suitable for carotenoids containing small amounts of impurities or other carotenoids. Hence this technique is useful for determining the molecular masses of carotenoids and the number of modifiable groups in carotenoids.     

Mass spectra of acyl and α-hydroxyalkyl derivatives of biferrocene

The mass spectral fragmentation pathways of acyl and α-hydroxyalkyl derivatives of biferrocene and related compounds are presented. A substituent effect for the cleavage of the cyclopentadienyl ring-metal bonds has been found in the spectra of acyl derivatives. It has been shown that the fragmentation of α-hydroxyalkyl derivatives proceeded via the ions corresponding to the [M]⁺? ions of oxidation or hydrogenolysis products of the hydroxyl derivatives.     

Phosphorylation of pyridoxal azomethines. Synthesis of phosphorus containing azomethines and furopyridines

New O-phosphorylated pyridoxal derivatives have been synthesized through the reaction of azomethines with Р^V acid chlorides. 2-Chloro-2-thioxo-5,5-dimethyl-1,3,2-dioxaphosphinanes and diethylchlorothiophosphate have been employed as phosphorylating agents. Regardless of the nature of the phosphorylating agent, the reaction is regioselective at phenolic hydroxyl group. The structure of final products is determined by the nature of the substituent at the nitrogen atom. If R is alkyl or cycloalkyl group, the products of the reaction represent phosphorylated pyridoxal imines, whereas phosphorylated furopyridines are formed in the case R is aryl substituent.     

Comprehensive characterization of surface-functionalized poly(amidoamine) dendrimers with acetamide,hydroxyl, and carboxyl groups

Terminal amine groups of poly(amidoamine) (PAMAM) dendrimers can be substituted with different functional groups for various applications. In this study, PAMAM derivatives with acetamide, hydroxyl, and carboxyl termini were synthesized from ethylenediamine (EDA) core generation 4 and 5 primary amine-terminated PAMAM dendrimers. The reaction products were purified with dialysis and subsequently characterized by polyacrylamide gel electrophoresis (PAGE), capillary electrophoresis (CE), size exclusion chromatography (SEC), matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, potentiometric titration, ¹H NMR, and ¹³C NMR. PAGE and CE electropherograms provide data regarding the purity, charge distribution, and electrophoretic mobility of the dendrimers and their derivatives. SEC and MALDI-TOF mass spectrometry detect the average absolute molar mass and the individual mass fractions, respectively. The combination of SEC with potentiometric titration provides quantitative evidence of the degree of the functional group substitution, while NMR techniques (both ¹H NMR and ¹³C NMR) confirmed the changes in dendrimer surface functionalization. This study provides a general example for the comprehensive characterization of surface-functionalized PAMAM dendrimer nanoparticles. The synthesized dendrimer derivatives hold promise for environmental and medical applications.     

Novel ester linked glycosyl amino acids: convenient building blocks for the synthesis of glycopeptide libraries

The completely orthogonally protected aspartic acid derivative FmocAsp(OBn)O^tBu is readily synthesized on a large scale. Deprotection of the β-carboxylic acid allows coupling to various sugar derivatives via free hydroxyl groups to produce novel glycosyl amino acids. Subsequent deprotection of either the α-acid or nitrogen is achieved cleanly to allow elaboration into an oligopeptide, whilst selective deprotection of PMB protected sugar hydroxyls is also readily achievable. Such novel glycosyl amino acid building blocks may be useful for the combinatorial synthesis of novel glycopeptide libraries.     

On the stereochemistry of 1,4-diheterocyclanes. IV—carbon-13 NMR spectra and structural properties of 1,4-dioxane-2,3-diols and their methyl-substituted derivatives

The 1,4-dioxane-2,3-diols and a number of their methyl-substituted derivatives were synthesized and their ¹³C NMR spectra measured. The configurational properties were studied on the basis of the spectral data and chemical equilibration. For the parent compound the trans configuration is slightly more stable. The hydroxyl groups are predominantly axial. Introduction of a methyl group at the 2 position causes the cis configuration of the hydroxyl substituents to become more stable. The substituent effects on the chemical shifts were calculated and used to test the conformational homogeneity of the compounds. The results indicate a biased (chair) conformation for all the methyl-substituted derivatives which were studied. Methyl groups have strongly predominating equatorial orientation in each case studied.     

Carbon-13 n.m.r. studies. 65—13C spectra of some tricyclo[3.2.1.02,4]octane derivatives

The ¹³C n.m.r. spectra of 18 derivatives of the tricyclo[3.2.1.0^2,4]octanes have been determined. This series includes methyl, hydroxyl and oxo substituted examples to compare the effects of these substituents on the skeletal carbon shieldings with those observed for the corresponding norbornanes and bicyclo[3.2.1]octanes. In general, the trends are similar and the perturbations associated with closely neighboring groups follow a consistent pattern. The shielding data for the exo–exo and exo–endo isomers of tetracyclo[3.3.1.0^2,40^6,8]nonane are also reported.     

Synthesis of benzaldehyde-functionalized LewisX trisaccharide analogs for glyco-SAM formation

LewisX (Le^x) antigen based carbohydrate–carbohydrate interactions are mediated by complexation of metal ions. Although theoretical studies about the influence of participating hydroxyl groups in the Le^x trisaccharide head group (Galβ(1-4)[Fucα(1-3)]GlcNAc) could gave same rudimental information about the basic mechanism behind this interaction, a little is known about orientation and configuration of the hydroxyl groups required for the specific interaction mediated by Ca²⁺ complexation. Therefore, there is a need of non-natural derivatives to provide detailed information about the requirements for hydroxyl group arrangement in Le^x head group surface plasmon resonance and gold nanoparticle techniques have shown to be powerful tools to investigate carbohydrate–carbohydrate interactions. Benzaldehyde-functionalized glycans can be used for attachment to both gold nanoparticles and surface plasmon resonance sensor surfaces. Therefore, seven benzaldehyde equipped Le^x analogs including the natural trisaccharide were synthesized utilizing convergent approach. The derivatives were applied in ongoing carbohydrate–carbohydrate interaction studies by surface plasmon resonance experiments to prove theoretical postulate about the structural requirements of hydroxyl group arrangements in Le^x trisaccharides.     

Carbon-13 NMR studies. 73—carbon-13 spectra of several 10-methyl-trans-decalins. Further definition of the deshielding antiperiplanar γ effect

The ¹³C spectra of a series of 21 10-methyl-trans-decalins have been recorded to explore in greater detail the deshielding antiperiplanar γ effects found earlier in a few of these derivatives. From the data for the series complete assignments for each compound were obtained, permitting an analysis of the shielding effects of the methyl and hydroxyl groups.     

One-Pot formation of novel [3+3] NH-CH2 bridged cyclophanes

The new [3+3] NH-CH₂ bridged cyclophanes bearing different functional groups and different cavity sizes were prepared in one pot by treating diamine derivatives with dialdehyde derivatives. Factors important for efficiently form-ing these macrocycles include reaction concentration (10 or 100?mmol), temperature (room temperature or 40–50?°C) and solvent (CHCl₃). Preliminary fluorescence spectrometer and HRMS-ESI studies demonstrated the inner cavity of the new [3+3] NH-CH₂ bridged cyclophanes bearing three hydroxyl groups (3c) as a new highly selective probe for the naked eye detection of Ag⁺ in PBS buffer.     

Efficient Regioselective Synthesis of Mono-2-O-Sulfonyl-cyclodextrins by the Combination of Sulfonyl Imidazole and Molecular Sieves

Abstract

Cyclodextrins are cyclic oligosaccharides consisting of six or more α-1,4-linked D-glucopyranose units, which possess primary hydroxyl groups at the C-6 positions and secondary hydroxyl groups at the C-2 and C-3 positions. Because cyclodextrins have a hydrophobic and optically active interior, they have been utilized as transporters of hydrophobic molecules and small molecular mimics of enzymes. The chemical modification of cyclodextrins has been investigated in order to improve these characteristics. Sulfonations of the primary or secondary hydroxyl groups of cyclodextrin have been applied for further functionalization of cyclodextrin, and several methods for regioselective sulfonations have been developed. Among these strategies, selective monotosylation of the C-6 hydroxyl group is done relatively easily by reaction of α or β-cyclodextrin and p-toluenesulfonyl chloride in pyridine^1,2 or in alkaline aqueous solution.^3,4 However, sulfonation of the secondary hydroxyl groups is more difficult and new sulfonation methods must be developed to provide precursors for cyclodextrin analogues such as amino and sulfide analogues. Several strategies for the sulfonation of one C-2 hydroxyl group have been reported. However, because reaction conditions can require specific sulfonation reagent,⁵ alkaline condition,^3-7 strict anhydrous conditions,^8,9 or use of protected C-6 hydroxyl groups,^10,11 the methodology is not convenient to employ.     

Easily functionalizable carbazole based building blocks with extended conjugated systems for optoelectronic applications

Carbazole based building blocks, possessing diphenylethenyl fragments, have been synthesized. Condensation of the carbazol-2-ol with diphenylacetaldehyde yields 1,3-substituted derivatives. Change of the synthesis sequence, however, (i.e., substitution at the hydroxyl and NH groups, followed by the condensation reaction) results in the 3,6-substituted products. Thermal, optical, electrochemical and photophysical properties of the synthesized derivatives have been investigated. Room temperature hole-drift mobilities, evaluated using xerographic time-of-flight technique, were found to exceed 10⁻⁴ cm² V⁻¹ s⁻¹ at strong electric fields. The obtained results indicate high charge mobility for molecularly doped polymers, especially considering the fact that these measurements were carried out under ambient conditions and not in high vacuum. Commercial availability and relative cheapness of the starting materials, simple synthetic method, number of sites available for easy functionalization and covalent linking to other molecules makes these precursors attractive building blocks for the construction of more complex low-molecular-weight or polymeric materials for optoelectronic applications.     

Syntheses and characterization of a new class of mono‐ and heterodinuclear derivatives of boron derived from Schiff bases

Reactions of 2‐isopropoxy‐1, 3, 2‐ benzodioxaborole with equivalent amounts of Schiff base ligands having two hydroxyl groups ( 1a–3a ) yield mononuclear derivatives with one residual hydroxy group. The reactions of these mononuclear derivatives with hexamethyldisilazane in a 2:1 ratio yield heterodinuclear derivatives. All these newly synthesized derivatives have been characterized by elemental analyses and molecular weight measurements. Tentative structures have been proposed on the basis of IR and NMR (¹H, ¹³C, ¹¹B,²⁹Si)spectral data and Fab‐mass studies. Schiff bases and their corresponding mono‐ and heterodinuclear derivatives of boron have also been screened for antifungal activities. Copyright © 2010 John Wiley & Sons, Ltd.     

Hydrophobic Derivatives of Dextran Polysaccharide: Characterization and Properties

This study reports the synthesis and characterization of hydrophobic derivatives of dextran in which long alkyl chains substituted a proportion of the hydroxyl groups. These derivatives were characterized by ¹³C and ¹H NMR and infrared spectroscopy. Information about hydrophobic associations in aqueous solutions was obtained by fluorescence spectroscopy in the presence of pyrene and nabumetone probes. These results, in addition to the swelling‐index data of derivatives, showed that there are perspectives of using them as a starting point for models of drug delivery.     

L-乳酸齐聚物的制备及其三羰基铼衍生物的合成

以L-丙交酯为原料, 通过正交保护基对其羧基、羟基进行修饰, 合成并表征了乳酸3个系列的12个化合物. 同时以合成得到的乳酸六聚体为原料, 合成并表征了羟基封端的聚乳酸-聚乙二醇-三齿螯合剂系列化合物, 并将其与[Et₄N]₂[Re(CO)₃Br₃]配位合成了其冷标记三羰基铼配合物. 产物通过IR, ¹H NMR, ¹³C NMR, ESI-HRMS, MALDI-HRMS或元素分析进行了表征. 该方法为扩展聚乳酸化学修饰法在材料科学中的应用奠定了基础. 此外分子量可控的乳酸-乙二醇结构铼配合物的设计合成扩展了其在分子影像科学的应用.     

Preparation of adamantyl derivatives of 1,4‐; 1,6‐ and 1,7‐dihydroxynaphthalenes and assignment of their NMR data

Adamantylation of dihydroxynaphthalenes with the hydroxyl groups on the same or different rings leads to compounds that are convenient starting materials in target‐oriented organic synthesis. Here, we report the ¹H and ¹³C NMR assignments of eight 1‐adamantyl substituted derivatives of 1,4‐; 1,6‐ and 1,7‐dihydroxynaphthalenes. The data acquired and peculiarities of their molecular structure are useful for extrapolation for prompt characterization of compounds containing adamantane, dihydroxynaphthalenes or naphthoquinone units. Copyright © 2013 John Wiley & Sons, Ltd.     

Cyclodextrin chemistry. Selective modification of all primary hydroxyl groups of α- and β-cyclodextrins

Two efficient methods are described for the selective modification of all six primary hydroxyl groups of α-cyclodextrin (α-CD, 1 1 ). One, using an indirect strategy, involves protection of all 18 hydroxyl functions as benzoate esters, followed by selective deprotection of the six primary alcohol groups. The other, using a direct strategy, involves selective activation of the primary hydroxyl groups via a bulky triphenylphosphonium salt, which is then substituted by azide anion as the reaction proceeds. A number of modified α-cyclodextrin derivatives have been prepared and fully characterized, among which are: the useful intermediate α-cyclodextrin-dodeca (2, 3) benzoate ( 3 ); hexakis (6-amino-6-deoxy)-α-cyclodextrin hexahydrochloride ( 7 ); hexakis (6-amino-6-deoxy)-dodeca (2, 3)-O-methyl-α-cyclodextrin hexahydrochloride ( 9 ), hexa (6)-O-methyl-α-cyclodextrin ( 13 ). The direct substitution is shown to be even more efficient for β-cyclodextrin ( 16 ), giving the heptakis (6-azido-6-deoxy)-β-CD-tetradeca (2, 3)acetate ( 17 ), while the indirect strategy fails. The compounds are characterized by extensive use of ¹³C- and ¹H-NMR. spectroscopy. The steric and statistical problems of selective polysubstitution reactions for the cyclodextrins are discussed, and possible reasons for the observed differences in reactivity between α- and β-cyclodextrins are examined. The dodecabenzoate 3 presents a very marked solvent effect on physical properties (IR. and NMR. spectra, optical rotation); the effects observed may be ascribed to an unusually strong intramolecular network of hydrogen bonds which severely distorts the α-cyclodextrin ring and lowers the symmetry from six-fold to three-fold.     

Structural Characterization of Oxidized Glycerophosphatidylserine: Evidence of Polar Head Oxidation

Non-oxidized phosphatidylserine (PS) is known to play a key role in apoptosis but there is considerable research evidence suggesting that oxidized PS also plays a role in this event, leading to the increasing interest in studying PS oxidative modifications. In this work, different PS (1-palmitoyl-2-linoleoyl-sn-glycero-3-phospho-L-serine (PLPS), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine (POPS), and 1,2-dipalmitoyl-sn-glycero-3-phospho-L-serine (DPPS) were oxidized in vitro by hydroxyl radical, generated under Fenton reaction conditions, and the reactions were monitored by ESI-MS in negative mode. Oxidation products were then fractionated by thin layer chromatography (TLC) and characterized by tandem mass spectrometry (MS/MS). This approach allowed the identification of hydroxyl, peroxy, and keto derivatives due to oxidation of unsaturated fatty acyl chains. Oxidation products due to oxidation of serine polar head were also identified. These products, with lower molecular weight than the non-modified PS, were identified as [M – 29 – H]^– (terminal acetic acid), [M – 30 – H]^– (terminal acetamide), [M – 13 – H]^– (terminal hydroperoxyacetaldehyde), and [M – 13 – H]^– (terminal hydroxyacetaldehyde plus hydroxy fatty acyl chain). Phosphatidic acid was also formed in these conditions. These findings confirm the oxidation of the serine polar head induced by the hydroxyl radical. The identification of these modifications may be a valuable tool to evaluate phosphatidylserine alteration under physiopathologic conditions and also to help understand the biological role of phosphatidylserine oxidation in the apoptotic process and other biological functions.     

Synthesis and NMR study of amide and imide derivatives of PMR-15 monomeric units

Variations in PMR-15 composite properties could be due to by-products formed during the polymerization cycle. In order to identify these compounds, various condensation products derived from the three monomeric constituents of the resin: NE, BTDE, and MDA, have been synthesized and fully characterized by spectroscopic methods, mainly by ¹H- and ¹³C-NMR. In these products, one or two MDA amino groups are replaced by amido or imido groups, leading to mono- and di-substituted MDA derivatives. Monosubstituted derivatives were obtained by first protecting one MDA amino group with a terbutoxycarbonyl group (Boc). The MDA's CH₂ bridge of these molecules gives rise, in their ¹H NMR spectra, to a characteristic resonance singlet, the position of which can be correlated to the nature of the amino substituents through ¹H chemical shift increments. The latter provide a useful tool to predict the CH₂, shifts in other compounds. Similar substituent increments are proposed for the chemical shifts of the MDA aromatic protons and carbon atoms.