Synthesis of Derivatives of ω-Isocyanato-α-methylamino, ω-Ureido-α-methylamino,and N<Superscript>α</Superscript>-Methyl-α, ω-diamino Acids

Summary.  Homochiral N^α-methyl-2,3-diaminopropionic and N^α-methyl-2,4-diaminobutyric acid derivatives 8a,b were obtained via a stereoconservative four-step synthesis starting from hexafluoroacetone protected L-aspartic and L-glutamic acid 2a,b, respectively. Hexafluoroacetone protected ω-isocyanato-α-methylamino acids 4a,b– the key intermediates of the synthesis – are versatile building blocks for amino acid and peptide modification and promising candidates for combinatorial chemistry. Upon reaction with alcohols, compounds 4 give activated N ^ω-urethane protected ω-amino-α-methylamino acid derivatives 5–7; upon reaction with amines, ω-ureido-α-methylamino acid derivatives 10–12 and 3-methylamino-pyrrolidin-2-ones 13 are available. Received November 17, 1999. Accepted November 26, 1999     

Enthalpies of solution of dl-α-alanyl-dl-α-asparagine in aqueous alcohols at 298.15 K

The enthalpies of solution of dl-α-alanyl-dl-α-asparagine (AlaAsn) were measured in aqueous methanol, ethanol, 1-propanol and 2-propanol with an alcohol mole-fraction content x₂ (from 0 to 0.4) at 298.15 K. The experimental results were used to calculate the enthalpies of transfer of AlaAsn from water to these mixtures as well as the enthalpy coefficients of pair-wise interactions (h_xy) between AlaAsn and alcohol molecules in water, according to the McMillan–Mayer's model. The h_xy values were found to be positive and increasing in a series methanol < ethanol < 1-propanol < 2-propanol.     

Fragmentation of <Emphasis Type="Italic">α</Emphasis>-radical cations of arginine-containing peptides

Fragmentation pathways of peptide radical cations, M^+·, with well-defined initial location of the radical site were explored using collision-induced dissociation (CID) experiments. Peptide radical cations were produced by gas-phase fragmentation of Co^III(salen)-peptide complexes [salen=N,N′-ethylenebis (salicylideneiminato)]. Subsequent hydrogen abstraction from the β-carbon of the side-chain followed by C_α-C_β bond cleavage results in the loss of a neutral side chain and formation of an α-radical cation with the radical site localized on the α-carbon of the backbone. Similar CID spectra dominated by radical-driven dissociation products were obtained for a number of arginine-containing α-radicals, suggesting that for these systems radical migration precedes fragmentation. In contrast, proton-driven fragmentation dominates CID spectra of α-radicals produced via the loss of the arginine side chain. Radical-driven fragmentation of large M^+· peptide radical cations is dominated by side-chain losses, formation of even-electron a-ions and odd-electron x-ions resulting from C_α-C bond cleavages, formation of odd-electron z-ions, and loss of the N-terminal residue. In contrast, charge-driven fragmentation produces even-electron y-ions and odd-electron b-ions.     

An aptameric molecular beacon-based “Signal-on” approach for rapid determination of rHuEPO-α

The aim of this work is to describe the first example of aptameric molecular beacon (MB)-based probe for the detection of recombinant human erythropoietin (rHuEPO-α) in physiological buffer, using a novel 35 nt ssDNA aptamer (807-35 nt) originally isolated by Systematic Evolution of Ligands by Exponential enrichment (SELEX) technique in our laboratory. Both “Signal-on” and “Signal-off” MB modes were developed, respectively, in which the conformational alteration of aptamer before and after binding to rHuEPO-α can be demonstrated in terms of the correspondingly fluorescent changes. Comparing with “Signal-off” mode, “Signal-on” mode provided higher sensitivity, while with the addition of target rHuEPO-α, quenching between fluorescent 807-35 nt aptamer (F-Apt) and a short quencher-labeled complementary sequence (QDNA) was disturbed by the specific binding between rHuEPO-α and F-Apt. QDNA was thus loosened and released from F-Apt, leading to a consequently full fluorescent restoration. Systematic optimization of parameters in “Signal-on” mode were carried out, the choice of QDNA length, the hybridization site of a small supplementary DNA (SDNA) stabilizer, and the existence of Mg²⁺ cation played essential roles for the performance characterization. A convenient and sensitive determination of rHuEPO-α with a LOD of 0.4 nM was achieved.     

Enantioselective synthesis of d-α-amino amides from aliphatic aldehydes

Peptides consisting of d-amino amides are highly represented among both biologically active natural products and non-natural small molecules used in therapeutic development. Chemical synthesis of d-amino amides most often involves approaches based on enzymatic resolution or fractional recrystallization of their diastereomeric amino acid salt precursors, techniques that produce an equal amount of the l-amino acid. Enantioselective synthesis, however, promises selective and general access to a specific α-amino amide, and may enable efficient peptide synthesis regardless of the availability of the corresponding α-amino acid. This report describes the use of a cinchona alkaloid-catalyzed aza-Henry reaction using bromonitromethane, and the integration of its product with umpolung amide synthesis. The result is a straightforward 3-step protocol beginning from aliphatic aldehydes that provides homologated peptides bearing an aliphatic side chain at the resulting d-α-amino amide.     

Highly enantioselective Michael addition of <Emphasis Type="Italic">α,α</Emphasis>-disubstituted aldehydes to nitroolefins

A highly enantioselective Michael addition reaction of α,α-disubstituted aldehydes to β-nitrostyrenes has been developed. In the presence of rosin-based chiral primary amine-thiourea, γ-nitroaldehydes were afforded in excellent enantioselectivities (up to 99 % ee) with up to 99 % yield.     

Effect of alkylated diphenylamine on thermal-oxidative degradation behavior of poly-<Emphasis Type="Italic">α</Emphasis>-olefin

An oil-soluble antioxidant, alkylated diphenylamine (ADPA), was prepared by alkylation of diphenylamine. The influence of ADPA on the thermal-oxidative stability of poly-α-olefin (PAO8) was evaluated by thermogravimetry (TG). For comparison, the thermal-oxidative stability of PAO8 with zinc dialkyl dithiophosphate (ZDDP) was also investigated. Activation energy (E_a)of the corresponding thermal-oxidative degradation process was evaluated by the Flynn-Wall-Ozawa (FWO) and Kissinger-Akahira-Sunose (KAS) methods. To demonstrate the reliability of the kinetic study, the antioxidant performance of ADPA and ZDDP in PAO8 was also studied by the pressure drop (PDT) and accelerated oxidation (AOT) tests. The results indicate that ADPA has better antioxidant ability than ZDDP in increasing the E_a value and enhancing the oxidative stability of PAO8. Good correlation between the applied test methods was established.     

FTIR study of adsorption and photodegradation of L-<Emphasis Type="Italic">α</Emphasis>-alanine on TiO<Subscript>2</Subscript> powder

An infrared study of the adsorption of L--alanine (L-Ala) on TiO₂ powder in aqueous suspension was carried out. When the amino acid is in the zwitterionic form and the TiO₂ surface is positively charged, experimental results indicated that L-Ala molecules are adsorbed on titania through the carboxylated group, which gives rise to a bridged structure with the positive centers (protonated hydroxyls) of the TiO₂ surface. Adsorbed amino acid was photodegradated in model conditions by exposing the sample to UV light through the quartz walls of the IR cell. The amine function was found to be preferentially removed from the adsorbed L-Ala molecules during the initial period of UV irradiation, and then the complete mineralization of the rest of the molecular structure occurred. This surface process agrees with the results of the analysis of the species that diffuse from the surface of the photocatalyst into the bulk of the liquid medium in the actual photodegradation carried out with TiO2 suspended in aqueous solutions of L-Ala.     

Kinetics of the outer-sphere oxidation of thiourea by heteropoly-α<Subscript>2</Subscript>-17-tungsto-1-vanadodiphosphate anion

Kinetics of the oxidation of thiourea (tu) by heteropoly-α₂-17-tungsto-1-vanadodiphosphate anion, α₂-[P₂V^VW₁₇O₆₂]^7?, have been studied spectrophotometrically in aqueous acidic medium at 25 °C. At low pH (2.4–3.0), the neutral form of tu is the only reactive species. At higher pH (4.2–4.9), both neutral and deprotonated forms of tu participate in the reaction. The observed mixed-order kinetics suggest two parallel reactions: one in which the order in [tu] is unity, and a second in which it is two. In both cases, the order in [α₂-[P₂V^VW₁₇O₆₂]^7?] is unity. Based on the kinetic studies, a mechanism is proposed, in which a second-order proton-coupled electron transfer involving NH₂CSNH₂ and α₂-[P₂V^VW₁₇O₆₂]^7? proceeds through a sequential electron transfer, followed by proton transfer such that the reaction is an “activation-controlled” outer-sphere electron transfer process. By applying the Marcus equation, the self-exchange rate constants for the couples \({\text{NH}}_{2} {\text{CSNH}}_{2}^{ \cdot + }\)/NH₂CSNH₂ and α₂-[P₂V^VW₁₇O₆₂]^7?/α₂-[P₂V^IVW₁₇O₆₂]^8? were evaluated.     

10<Emphasis Type="Italic">α</Emphasis>-Hydroxy-<Emphasis Type="Italic">β</Emphasis>-isomorphine,a by-product of the synthesis of 10<Emphasis Type="Italic">α</Emphasis>-hydroxymorphine

Abstract  A new compound was isolated from the reaction mixture after O-demethylation of 6-O-acetyl-10α-acetoxycodeine with boron tribromide. The structure of this compound, 10α-hydroxy-β-isomorphine, was elucidated by spectral data, and its spatial arrangement was deduced from an NOE experiment. Capillary zone electrophoresis was used for separation of morphine and its 10-hydroxy analogues. Graphical abstract        

Synthesis of <Emphasis Type="Italic">α</Emphasis>-chloropyridine derivatives of <Emphasis Type="Italic">γ</Emphasis>-aminobutyric acid

The sodium salt of N-(6-chloronicotinoyl)-γ-aminobutyric acid, a structural analog of the known nootropic and vasidilating drug picamilon, was synthesized via Schotten–Baumann acylation of γ-aminobutyric acid with 6-chloronicotinoyl chloride and subsequent neutralization of the N-(6-chloronicotinoyl)-γ-aminobutyric acid that was obtained in >60% yield.     

Synthesis and antituberculosis activity of certain steroidal derivatives of the 5<Emphasis Type="Italic">α</Emphasis>-series

The antituberculosis activity of several steroidal compounds of various structure was studied. Severa compounds that were active toward M. tuberculosis were found in in vitro tests. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 500–501, September-October, 2008. Original article submitted July 10, 2008.     

Influence of metal cation on chromophore properties of complexes of some <Emphasis Type="Italic">d</Emphasis> metals with α,α-dipyrrolylmethene

In complexes of Cu²⁺, Ni²⁺, Co²⁺, Zn²⁺, and Hg²⁺ with 3,3,5,5-tetramethyl-4,4-dibutyl-2,2-dipyrrolylmethene, the d-metal ion exerts an auxochromic effect on the system of the ligand, manifested in a bathochromic shift of the first absorption band in the spectrum of the complex, compared to the free ligand. Polarization of the chromophore system in the complexes increases in the order Zn²⁺ < Hg²⁺ < Co²⁺ < Ni²⁺ < Cu²⁺. The Hg²⁺ ion in the complex with dipyrrolylmethene participates in mercuration of benzene and chloroform; the reaction with chloroform is faster, with the rates of both reactions strongly depending on temperature.Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 8, 2004, pp. 1383–1387.Original Russian Text Copyright © 2004 by Guseva, Antina, Berezin, Vyugin.This revised version was published online in April 2005 with a corrected cover date.     

Blocking group-directed diastereoselective total synthesis of (±)-α-noscapine

A new approach for the diastereoselective synthesis of (±)-α-noscapine, a phthalide tetrahydroisoquinoline alkaloid exhibiting several biological activities, is described. The strategy features a blocking group-directed Bischler-Napieralski reaction followed by diastereoselective reduction (α/β>23:1). One of the key intermediates, phthalide-3-carboxylic acid, could be efficiently prepared from simple benzoic acid derivative and glyoxylic acid in one-pot.     

One-pot green synthesis and cytotoxicity of new <Emphasis Type="Italic">α</Emphasis>-aminophosphonates

A novel series of α-aminophosphonates containing the trifluoromethyl aniline moiety were obtained in high yields by condensation of 2-methyl-3-trifluoromethyl aniline, aryl/heteroaryl aldehydes and dimethylphosphite in the presence of chitosan as a catalyst. The molecular modeling studies revealed their important structural features of binding affinities towards the target enzyme. The cytotoxicity of these compounds was evaluated against PC-3(prostate cancer), MCF-7 (breast cancer), HeLa(cCervix Cancer), U973, K562 and HL60 human lLeukemia cell lines. Compound 4k with a pyrene moiety showed high potency against a breast cancer cell line, while compounds 4g and 4k exhibited more promising cytotoxicity against U973, K562 and HL60 cell lines.     

The thermochemical characteristics of solutions of Cu(NO<Subscript>3</Subscript>)<Subscript>2</Subscript> in water-formamide-α-L-alanine mixtures at 298 K

The enthalpies of mixing of aqueous solutions of copper(II) nitrate with aqueous solutions of formamide and α-L-alanine were measured calorimetrically over the whole composition range with respect to amide. The results were used to calculate the standard enthalpies of electrolyte transfer from water into ternary mixtures. The shape and character of electrolyte transfer isotherms are discussed on the basis of the enthalpies of transfer of individual ions studied earlier in a binary solvent and the contributions of universal and chemical interactions between the ion and solvents to these values characterizing structural changes in solution.     

Aromaticity and diatropicity of <Emphasis Type="Italic">p</Emphasis>-polyphenyl-α,ω-quinododimethides

p-Polyphenyl-α,ω-quinododimethides were predicted to be moderately aromatic and diatropic, although they exist only in a single classical resonance structure with no aromatic conjugated circuits. Such a dichotomy was resolved using our graph theory of aromaticity and ring-current diamagnetism. Six-site non-conjugated circuits were found to contribute appreciably to aromaticity and ring-current diamagnetism. Within each quinododimethide molecule, local aromaticity increases on going from the outermost to inner phenylene rings.     

Synthesis and properties of siRNAs containing 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleosides

Short interfering RNAs (siRNAs) containing P3′→N5′ phosphoramidate linkages were successfully synthesized by introducing 2′-deoxy-2′-fluororibonucleoside and 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleoside in succession. It was found that the introduction of 5′-amino-2′,5′-dideoxy-2′α-fluororibonucleosides into siRNAs improved the nuclease-resistant properties of the siRNAs without loss of their silencing efficacy.