Glycoconjugates of amino acids. Preparation throughN-alkylation of amino acids withN-chloroacetyl-β-glycopyranosylamines

Monoalkylation of amino acids of different structural types withN-chloroacetyl-glycosylamines was shown to be applicable for the preparation of glycoconjugates containing β-d-galactose,N-acetyl-β-d-glucosamine, β-d-mannose, and lactose residues. The glycoconjugates were synthesized from amino acids with secondary (sarcosine,l-proline) or primary (l-2- and 4-aminobutyric acids,l-tryptophan) amino groups as well as from various amino dicarboxylic acids (N-methyl-dl-aspartic,dl-aspartic,l-glutamic, anddl-2-aminoadipic acids). The derivatives obtained may be of interest for glycotargeting of physiologically active compounds of this series. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1377–1380, July, 1999.     

The synthesis ofN-acetyl-β-l-fucosamine-1-phosphate and uridine 5′-diphospho-N-acetyl-β-l-fucosamine

Uridine 5′-(2-acetamido-2,6-dideoxy-β-l-galactopyranosyl) diphosphate (uridine 5′-diphospho-N-acetyl-β-l-fucosamine) was synthesized. The key intermediate, 3,4-di-O-acetyl-2-azido-2,6-dideoxy-β-l-galactopyranosyl dibenzyl phosphate, was prepared by a previously unknown reaction of cesium dibenzyl phosphate with the corresponding α-glycosyl nitrate and was then converted into theN-acetylated glycosyl phosphate and nucleoside diphosphate sugarsvia 3,4-di-O-acetyl-2-amino-2,6-dideoxy-β-l-galactopyranosyl phosphate using mildN-acetylation andO-deacetylation as the last synthetic steps. Published inIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 11, pp. 1919–1923, November, 2000.     

Temperature- and pressure-responsive properties of <Emphasis Type="SmallCaps">l</Emphasis>- and<Emphasis Type="SmallCaps"> dl</Emphasis>-forms of poly(<Emphasis Type="Italic">N</Emphasis>-(1-hydroxymethyl)propylmethacrylamide) in aqueous solutions

The structural transition of the l- and dl forms of poly(N-(1- hydroxymethyl)propylmethacrylamide (PHMPMA) in aqueous solution was studied by measuring the pressure dependence of the apparent scattering intensity, differential scanning calorimetry (DSC), and circular dichroism (CD). The thermodynamic implications of the results are discussed in relation to the chiral structure of the side chain, and differences in the thermal and barometric transitions. T-P diagrams of the transition showed characteristic ellipsoid features. Antagonism of the temperature and pressure effects was observed only for P(dl-HMPMA). For P(l-HMPMA), the transition temperature (T _tr) decreased with increasing pressure, and the highest T _tr was observed at atmospheric pressure (0.1 MPa). For both polymers, the highest P _trs were observed at the lowest temperatures. The l polymer showed a specific negative peak in its CD spectrum at around 220 nm in the lower temperature region and the temperature dependence was reproduced by a single-step transition, with the midpoint corresponding to the T _tr obtained from the scattering measurements. Coupled with the results from the DSC, the different behavior between the P(l-HMPMA) and P(dl-HMPMA) could be explained in terms of the chain states before and after the transition. The cooperative factors derived from the DSC measurement revealed that about 4 to 5 polymers of the present size were necessary to perform a thermal transition for P(l-HMPMA), and that P(dl-HMPMA) underwent its transition as an almost single molecular event.This revised version was published online in June 2005 with correction to the article category.     

Amino acids in aqueous solution. Effect of molecular structure and temperature on thermodynamics of dissolution

The enthalpies of dissolution of glycine (Gly) and L-α-alanine (Ala) in water at 288.15–318.15 K were measured. The results were compared with the earlier obtained data for L-α-phenylalanine (Phe) and L-α-histidine (His). The standard enthalpies of dissolution (Δ_soln H ₀) and differences (ΔC _p ⁰ ) between the limiting partial molar heat capacity of the amino acids in solution and the heat capacity of the amino acids in the crystalline state were calculated in the temperature interval 273–373 K. Changes in the entropy of dissolution (ΔΔ_soln S ₀) and reduced Gibbs energy [Δ (Δ_soln G ₀/T)] in the temperature interval from 273 to 373 K were determined from the known thermodynamic relationships. The ΔC _p ⁰ value is negative for hydrophilic glycine and positive for other amino acids. The ΔΔ_soln S ⁰ values increase with an increase in the hydrophobicity of the amino acids. The Δ(Δ_soln G ₀/T) values become more negative in the order Ala, Phe, Gly, His. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 711–714, April, 2007.     

New polyhydroxysteroids and steroid glycosides from the far east starfishCeramaster patagonicus

Two new polyhydroxysteroids and five new glycosides were isolated from the starfishCeramaster patagonicus and their structures were elucidated: 5α-cholestane-3β,6α,15β,16β,26-pentol, (22E)-5α-cholest-22-ene-3β,6α,8,15α,24-pentol, (22E)-28-O-[O-(2-O-methyl-β-d-xylopyranosyl)-(1→2)-β-d-galactofuranosyl]-24-hydroxymethyl-5α-cholest-22-ene-3β,4β, 6α,8,15β,16β,28-heptol (ceramasteroside C₁), (22E)-28-O-[O-(2,4-di-O-methyl-β-d-xylopyranosyl)-(1→2)-β-d-galactofuranosyl]-24-hydroxymethyl-5α-cholest-22-ene-3β, 6α,8,15β,16β,28-hexol (ceramasteroside C₂), (22E)-28-O-[O-methyl-β-d-xylopyranosyl)-(1→2)-β-d-galactofuranosyl]-24-hydroxymethyl-5α-cholest-22-ene-3β,6α,8,15β,16β 28-hexol (eramasteroside C₃), (22E)-28-O-[O-(2-O-methyl-β-d-xylopyranosyl)-(1→2)-β-d-galactofuranosyl]-24-methyl-5α-cholest-22-ene-3β,4β,6α,8, 15β, 26-hexol (ceramasteroside C₄), and (22E)-28-O-[O-(2-O-methyl-β-d-xylopyranosyl)-(1→2)-β-d-xylopyranosyl]-5α-cholest-22-ene-3β,6α,8,15β,24-pentol (ceramasteroside C₅)). Three known polyhydroxysteroids (24-methylene-5α-cholestane-3β,6α,8,15β,16β,26-hexol, 5α-cholestane-3β,6α,8,15β,16β,26-hexol, and 5α-cholestane-3β,6β,15α,16β,26-pentol) were also isolated. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 190–195, January, 1997.     

Asterosaponin P2 from the Far-Eastern starfishpatiria (asterina) pectinifera

A new polyhydroxylated steroidal glycoside, asterosaponin P₂, was isolated from the Far-Eastern starfishPatiria (Asterina) pectinifera. The glycoside was identified as the 24R)-29-O-[2-O-sulfo-α-L-arabinofuranosyl]-24-ethyl-5α-cholestane-3β, 6α,8β,15α,16β,29-hexol Na salt. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1818–1820, October. 2000     

An easy access to a 3,6-branched mannopentaoside bearing one terminal [1-<Superscript>13</Superscript>C]-labeled <Emphasis Type="SmallCaps">D</Emphasis>-mannopyranose residue

Methyl 2,4-di-O-benzoyl-α-D-mannopyranoside was used as a key intermediate in the synthesis of 3,6-branched mannopentaoside bearing one terminal D-[1-¹³C]mannopyranose residue, viz., methyl 6-O-[3,6-di-O-(α-D-mannopyranosyl)-α-D-mannopyranosyl)-3-O-{α -D-[1-¹³C]mannopyranosyl}-α-D-mannopyranoside. Dedicated to Academician N. K. Kochetkov on the occasion of his 90th birthday. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1250–1255, May, 2005.     

Marked differences between acetonitrile/water and methanol/water mobile phase systems on the thermodynamic behavior of benzodiazepines in reversed phase liquid chromatography

Summary Two different methods were used to determine the separation factor α at different temperatures and the Gibbs-Helmholtz parameters (Δ(ΔH), Δ(ΔS)) of two adjacent benzodiazepines on a chromatogram were obtained from plots of lnα versus 1/T. We first studied each factor (fraction of water ϕ in the ACN/water mixture and column temperatureT), which controls the retention mechanism, and then we examined the simultaneous variation of all these factors. The changes in Δ(ΔH) and Δ(ΔS) in relation to a volume fraction of water ϕ in an ACN/water mixture were examined. In the ACN/water system, Δ(ΔH) was fairly constant in the acetonitrile region of ϕ≤0.52 and appears to be a roughly linear function of ϕ for ϕ≥0.52. In this system Δ(ΔS) is approximately a parabolic function of ϕ with an optimum at ϕ≊0.52. The retention mechanism of ten benzodiazepines was found to be significantly different in the methanol/water and ACN/water mixtures. The separation optimization of these ten benzodiazepines was then considered. A fraction of water of 0.43 in the ACN/water mixture and a column temperature of 44 °C gave the most efficient separation conditions in the ACN/water mixture.     

Polar steroidal compounds from the Far-Eastern starfish <Emphasis Type="Italic">Lethasterias fusca</Emphasis>

Nine steroidal compounds including three new steroidal glycosides, viz., sodium (24S)-3,24-di-O-(β-D-xylopyranosyl)-5α-cholestane-3β,6β,8,15α,24-pentol 15-sulfate (fuscaside A), (24S)-3,24-di-O-(β-D-xylopyranosyl)-5α-cholestane-3β,6β,8,15α,24-pentol (fuscaside B), and (22E,24R)-24-O-(β-D-xylopyranosyl)-5α-cholest-22-ene-3β,6α,8,15β,24-pentol (desulfated minutoside A); three previously known glycosides, viz., distolasterosides D₁ and D₂ and pycno-podioside A; two previously known polyhydroxysteroids, viz., 5α-cholestane-3β,6α,8,15β,16β,26-hexaol and 5α-cholestan-3β,4β,6α,7⇇8,15β,16β,26-octol; and the known sodium 24,25-dihydro-marthasterone 3-sulfate were isolated from the Far-Eastern starfish Lethasterias fusca. The structures of these compounds were elucidated by NMR spectroscopy and mass spectrometry. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 196–200, January, 2008.     

Preparation of optical active aliphatic <Emphasis Type="Italic">α</Emphasis>-amino acid from fatty acid: synthesis of <Emphasis Type="SmallCaps">l</Emphasis>-norvaline and <Emphasis Type="SmallCaps">d</Emphasis>-norvaline

A new synthesis of l-norvaline is described. Using valeric acid as the raw material, α-brominevaleryl chloride was achieved by acyl chlorination and α-position bromination in one-pot with the yield of 84.7%. The yields of the following ammoniation of α-brominevaleryl chloride and resolution of dl-norvaline were 88.7% and 26.7%, respectively. d-Norvaline was also obtained in a similar method from the waste resolution solution. Other optical active amino acids, valine, α-aminobutyric acid and alanine were also synthesized in similar ways.     

Stereospecific mannosylations of myo -inasitol: Synthesis of manno- myo -inositol fragment of Mycobacterium tuberculosis

Methyl iodide activated stereospecific α-mannosylations utilising 2-pyridyl-1-thiomannopyranoside derivatives (2,3,4) as donors and suitably protected myo-inositol derivatives (1,25,27,29) as acceptors to prepare 2-0-α-D-mannopyranosyl-6-[O-α-D-mannopyranosyl-(1–6)-O-α-D-mannopyranosyl-(l-6)-O-α-D-mannopyranosyl]-D-myo-inositol derivative (31) is described. IICT Commun. No. 3355     

Glycosylation of betulin acetates with glycals

Betulin 2-deoxy-α-d-, 2-deoxy-α-l-, and 2,6-dideoxy-α-l-arabino-hexopyranosides were synthesized by acid-catalyzed glycosylation (cationite in the H⁺ form, LiBr) of betulin 3- and 28-monoacetates with glycal acetates. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 531–534, March, 1998.     

Purification and characterization of an extracellular α-l-arabinofuranosidase from Fusarium oxysporum

An α-l-arabinofuranosidase from Fusarium oxysporum F3 was purified to homogeneity by a two-step ion exchange intercalated by a gel filtration chromatography. The enzyme had a molecular mass of 66 kDa and was optimally active at pH 6.0 and 60°C. It hydrolyzed aryl α-l-arabinofuranosides and cleaved arabinosyl side chains from arabinoxylan and arabinan. There was a marked synergistic effect between the α-l-arabinofuranosidase and an endo-(1 →4)-β-d-xylanase produced by F. oxysporum in the extensive hydrolysis of arabinoxylan.     

Separation ofN-carbamoyl aspartate andl-dihydroorotate from serum by high-performance liquid chromatography with fluorimetric detection

Summary A high-performance liquid chromatographic method, with 9-anthryldiazomethane as derivatizing agent, has been developed for the simultaneous determination ofN-carbamoyl aspartate andl-dihydroorotate in serum. Sample preparation for 1 mL serum was by simple liquid-liquid extraction and then derivatization. The compounds were separated on a Luna C18(2) column by use of a gradient prepared from acetonitrile and 10 mM sodium acetate buffer, pH 6.0, and fluorimetric detection was performed at excitation and emission wavelengths of 365 nm and 412 nm, respectively. The response was found to be linearly dependent on concentration between 0.8 and 60 μg mL⁻¹ forl-dihydrooratate and between 0.9 and 90 μg mL⁻¹ forN-carbamoyl aspartate; the mean recovery rates were 50 and 51%, respectively. The limits of detection and quantification were 0.33 μg mL⁻¹ and 0.6 μg mL⁻¹, respectively, forl-dihydroorotate and 0.4 μg mL⁻¹ and 0.7 μg mL⁻¹ forN-carbamoyl aspartate. This method can be used to assess accumulation ofN-carbamoyl aspartate andl-dihydroorotate in body fluids in situations where cellular pyrimidine de novo synthesis is impaired.     

Stereoselective synthesis of triterpene 2-deoxy-α-d-lyxo-hexopyranosides

2-Deoxy-α-d-lyxo-hexopyranosides of 18β-glycyrrhetic acid, its 11-deoxo derivative and allobetulin were synthesized by glycosylation of oleonane-type triterpene alcohols withd-galactal acetate in the presence ofN-iodosuccinimide followed by deiodination and deprotection. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 596–600. March, 1997.     

Separation of new antidiabetic agent,N-(trans-4-isopropylcyclohexylcarbonyl)-d-phenylalanine and three related compounds by RP-HPLC

Summary A high-performance liquid chromatographic method is proposed for the simultaneous separation of two pairs of isomers:N-(trans-4-isopropylcyclohexylcarbonyl)-d-phenylalanine, (Nateglinide) andN-(cis-4-isopropylcyclohexylcarbonyl)-d-phenylalanine,trans-4-isopropylcyclohexane-carboxylic acid andcis-4-isopropyl-cyclohexanecarboxylic acid using a C₁₈ column. The mobile phase is a ternary mixture of acetonitrile-methanol-0.1 M ammonium dihydrogen phosphate buffer, pH 3.0 (5:2:4 v/v/v) and UV detection at 210 nm. Precision, linearity, limit of detection and recovery were also evaluated for each compound. Satisfactory results were obtained.     

Thermodynamics of Nicotinic Acid Interactions with Some Saccharides

The interactions of nicotinic acid with α-D-glucose and maltose, and with α-, β-, hydroxypropyl-α- and hydroxypropyl-β-cyclodextrins were studied by using solution calorimetry at T = 298.15 K and pH = 3.4. The thermodynamic parameters (log₁₀ K, Δ G∘_c, Δ H∘_c and Δ S∘_c) were calculated for the systems in which complex formation was observed. Systems with weak interparticle interactions lacking complex formation were characterized by enthalpic virial coefficients calculated on the basis of the McMillan–Mayer theory. It was found that the complexation affinity of α-cyclodextrin to nicotinic acid is stronger in comparison to β-cyclodextrin and the mono- and disaccharides. The influence of different factors, such as the availability of the macrocyclic hydrophobic cavity, the relationship of the sizes of guest molecule to the host cavity, the presence of bulky hydroxypropyl substitutes and their structure, and the solvation of guest molecules on the stability of complexes and their thermodynamic parameters of interaction is discussed.     

Effective synthesis of methyl 3β-amino-3-deoxybetulinate

A practical method for preparing methyl 3β-amino-3-dexoybetulinate that is based on column chromatographic separation of 3α- and 3β-t-butoxycarbonates and subsequent removal of the protecting group using formic acid is proposed. The structure of methyl 3β-N-(t-butoxycarbonyl)-3-deoxybetulinate was established by an x-ray structure analysis. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 488–490, September-October, 2008.     

Asymmetric synthesis ofS-alkyl-substituted (R)-cysteinesvia a chiral NiII complex of the Schiff's base of dehydroalanine with (S)-2-N-(N-benzylprolyl)aminobenzophenone

An efficient procedure was developed for the asymmetric synthesis ofS-alkyl derivatives of (R)-cysteine by nucleophilic addition of alkanethiols (BuⁿSH, Bu^tSH, ortert-C₅H₁₁SH) to the C=C bond of the dehydroalanine fragment in the Ni^II complex of the Schiff's base of Δ-Ala with (S)-2-N-(N-benzylprolyl)aminobenzophenone [(S)-BPB-Δ-Ala]Ni^II. Under conditions of thermodynamic control of the reaction, the diastereomeric excess of the complexes with the (S.R)-configuration was 88–96%. After decomposition of the complexes,(R)-S-butylcysteine,(R)-S-tert-butylcysteine, and(R)-S-tert-pentylcysteine were isolated with an enantiomeric purity of >97%. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1467–1470, August, 2000.     

A new hexahydroxysteroid from the Far Eastern starfishLuidiaster dawsoni

A new polyhydroxysteroid was isolated from the starfishLuidiaster dawsoni; the structure of the product was established as (24S,25R)-24-methylcholestane-3β, 5α, 6β, 15α, 16β, 26-hexaol. A mixture of methyl-α- and β-d-glucopyranosides was also isolated from the extract of this starfish. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2088–2090, October, 1998.