Use of Ferric Chloride in Carbohydrate Reactions.1 Iv. Acetolysis of Benzyl Ethers of Sugars

Acetolysis of benzyl ethers of sugars has been carried out with anhydrous ferric chloride in acetic anhydride. By employing this reagent, benzyl ether groups variously placed in sugars or in their glycosides could be removed with ease and replaced by acetyl groups. By controlled acetolysis, preferential removal of certain benzyl groups was possible. The results show that in D-glucose the relative ease of removal of benzyl ether groups by acetolysis follows the order C-6 > C-4 > C-3 > C-2 and that the rate of acetolysis is 6-O-Bn : 3-O-Bn : 2-O-Bn = 125 : 24 : 1. The corresponding methyl ethers were very sluggish towards acetolysis.     

Protecting‐Group‐Controlled Enzymatic Glycosylation of Oligo‐N‐Acetyllactosamine Derivatives

We describe a chemoenzymatic strategy that can give a library of differentially fucosylated and sialylated oligosaccharides starting from a single chemically synthesized tri‐N‐acetyllactosamine derivative. The common precursor could easily be converted into 6 different hexasaccharides in which the glucosamine moieties are either acetylated (GlcNAc) or modified as a free amine (GlcNH₂) or Boc (GlcNHBoc). Fucosylation of the resulting compounds by a recombinant fucosyl transferase resulted in only modification of the natural GlcNAc moieties, providing access to 6 selectively mono‐ and bis‐fucosylated oligosaccharides. Conversion of the GlcNH₂ or GlcNHBoc moieties into the natural GlcNAc, followed by sialylation by sialyl transferases gave 12 differently fucosylated and sialylated compounds. The oligosaccharides were printed as a microarray that was probed by several glycan‐binding proteins, demonstrating that complex patterns of fucosylation can modulate glycan recognition.     

Chemical modification of hydroxyl groups of poly(vinyl alcohol) by a glycosidation reaction

A new procedure for chemical modification of poly(vinyl alcohol) (PVA) was established by a glycosidation reaction of hydroxyl groups in PVA with triacetylated sugar oxazoline 1 . ¹H and ¹³C NMR analyses indicated that triacetylated N‐acetyl‐D‐glucosamine (GlcNAc) was introduced onto a PVA backbone selectively via a β‐O‐glycoside linkage. Deacetylation of triacetylated GlcNAc‐substituted PVA 2 resulted in GlcNAc‐substituted PVA 3 in good yield. These modified PVAs 2 and 3 exhibited solubilities and thermal properties different from the original PVA.     

Synthesis of 4-Epi-L-Rhodosamine Containing Disaccharide

Abstract

Condensation of benzyl 3-azido-2,3,6-trideoxy-α-L-arabino-hexopyranoside (9) with 3,4-di-O-acetyl-2-deoxy-L-fucosyl chloride (10) gave 11. Catalytic hydrogenation of 11 followed by N,N-dimethylation of 12 and deprotection afforded the benzyl glycoside of the title compound, 2-deoxy-L-fucose (1 ? > 4) 4-epi-L-rhodosamine, 14.     

Alkylation of salts ofN-(β-hydroxyalkyl)-N′-hydroxydiazeneN-oxides with alkyl halides and dimethyl sulfate

Salts ofN-(β-hydroxyalkyl)-N′-hydroxydiazeneN-oxides, RCH(OH)CH₂N(O)=NO⁻ M⁺ (R=Me, Prⁱ, or Bu^t; and M=Li, Na, K, Ag, NH₄, or Me₄N), were prepared. Their alkylation with alkyl halides R′X (X=Cl, Br, or I) and dimethyl sulfate was studied. Generally, alkylation afforded mixtures ofN-(β-hydroxyalkyl)-N′-alkoxydiazeneN-oxides RCH(OH)CH₂N(O)=NOR′ andO-alkyl-N-(β-hydroxyalkyl)-N-nitrosohydroxylamines RCH(OH)CH₂N(NO)OR′. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1996–2001, October, 1998.     

Synthesis and DFT Defined trans (O5O6) Molecular Structure of Cs[Fe(1,3- pddadp )] · 2H2O. Strain Analysis and Spectral Assignment of the Complex

An iron(III) complex with the hexadentate ligand 1,3-propanediamine-N,N′-diacetate-N,N′-di-3-propionate (1,3-pddadp) was prepared, chromatographically isolated as its isomer trans(O₅O₆)-Cs[Fe(1,3-pddadp)] · 2H₂O, and characterized. The trans(O₅O₆) configuration of the iron(III) compound was found to dominate and this geometry was established by means of IR spectroscopy and Density Functional Theory (DFT). Structural data correlating the octahedral geometry of the [Fe(1,3-pddadp)]⁻ unit and an extensive strain analysis are discussed in relation to the information obtained for similar complexes. Antibacterial activities of the free ligand and its corresponding iron(III) complex towards common Gram-negative and Gram-positive bacteria are reported as well.     

Ion-neutral complexes resulting from dissociative protonation: Fragmentation of <Emphasis Type="Italic">α</Emphasis>-furanylmethyl benzyl ethers and 4-<Emphasis Type="Italic">N,N</Emphasis>-dimethylbenzyl benzyl ethers

The loss of CH₂O during mass spectrometry in two series of α-aromaticmethyl benzyl ether compounds, namely, α-furanylmethyl p-substituted-benzyl ethers and 4-N,N-dimethylbenzyl p-substituted-benzyl ethers, is particularly interesting. The fragmentation mechanism is proposed to involve an ion-neutral complex-mediated pathway. Specifically, before the formation of an ion-neutral intermediate, the proton is transferred from the thermodynamically favored site at either the ether oxygen atom or the nitrogen atom to the dissociative protonation site at C_α position in either the furyl group or the 4-N,N-dimethylphenyl group. This transfer has been clarified via computational studies and isotopically labeled experiments. In addition, the decomposition of the intermediate may be affected by the substituent groups on the phenyl ring. This conclusion is indicated by the reasonably good correlation between ln[([M + H − CH₂O]⁺)/([M + H − CH₂O − C₆H₅R]⁺)] and the substituent constants.     

Theoretical study of the structure and stability of the dimers of heme analogues (MC34H32N4O4)2 and their ions (MC34H32N4O4) 2+ with 3 d -metal atoms M

The electronic and geometric structures and the energetic characteristics of a series of monomeric MC₃₄H₃₂N₄O ₄ ^0,+ and dimeric (MC₃₄H₃₂N₄O₄) ₂ ^0,+ molecules, heme analogues and their positively charged ions with 3d-metal atoms M = Ti, V, Cr, and Mn, have been calculated by the density functional theory B3LYP method with the Gen−1 = 6−31G^*(Fe) + 6−31G(C, H, N, O) and Gen−2 = 6−311+G^*(Fe) + 6−31G^*(C, H, N, O) basis sets. The computation results are compared with the analogous calculated data on the heme dimers (heme) ₂ ^0,+ . Computations show that for the (MC₃₄H₃₂N₄O₄) ₂ ^0,+ dimers, high-spin states are preferable. In these dimers, the rings are linked with each other by a pair of M-carbonyl bridges M⋯O_b=C(OH) and a pair of hydrogen bridges OH_b⋯N. The calculated energies of dissociation D of the dimers into monomers point to a rather high stability of the dimers at the beginning of the 3d series (D ∼ 2.3–3.6 eV for M = Ti, V), which decreases rapidly as the atomic number of M increases (D ∼ 0.5 eV for M = Cr and ∼0.4 eV for (heme)₂). The positive ions (MC₃₄H₃₂N₄O₄) ₂ ⁺ are ∼0.8–1.0 eV are more stable to dissociation than their neutral congeners (MC₃₄H₃₂N₄O₄)₂. The trends in the behavior of the energetic and structural characteristics of the dimers (distances R(M—N), displacements of M atoms from the porphyrin ring plane, parameters of the carbonyl and hydrogen bridges, character of ring distortions, etc.), as well as in the spin density distribution between the metal atoms and the rings in the monomers MC₃₄H₃₂N₄O₄ and dimers (MC₃₄H₃₂N₄O₄)₂ caused by their ionization and going along the 3d series, are examined. In the mixed dimer (FeC₃₄H₃₂N₄O₄)(VC₃₄H₃₂N₄O₄), the rings are linked by only one strong carbonyl bridge V⋯O_b=C(OH), with some contribution made by the neighboring hydrogen bridge. The dissociation energy of this mixed dimer into monomers is close to a half of the dissociation energy of the “symmetric” dimer (VC₃₄H₃₂N₄O₄)₂. Original Russian Text ? O.P. Charkin, N.M. Klimenko, D.O. Charkin, S.H. Lin, 2007, published in Zhurnal Neorganicheskoi Khimii, 2007, Vol. 52, No. 8, pp. 1332–1346.     

Prearranged Glycosides,Part 10. Intramolecular Glycosylation with Cellobiosyl,Lactosyl, and Maltosyl Donors

ABSTRACT

Acetyl protected 1,2-O-(1-methoxyethylidene)-disaccharides 1 of maltose, cellobiose, and lactose, respectively were converted via the corresponding benzyl protected couterparts 2, the benzyl protected phenyl 2-O-acetyl- 3 and 2-O-unprotected 1-thio-glycoside disaccharides 4 into 2-O-succinoylated disaccharides 5. The latter were esterified with benzyl 2-O-benzoyl-4,6-di-O-benzylidene-α-D-glucopyranoside (6) to afford succinyl linked derivatives 7 the benzylidene groups of which were regioselectively opened to give prearranged glycoside trisaccharides 8. Intramolecular glycosylation of the latter with N-iodosuccinimide resulted in exclusive formation of the corresponding α-(1→4)-linked trisaccharides 9. No influence of the donor moiety on the diastereoselectivity of the intramolecular glycosylation was observed.     

N7-DNA: Synthesis and Base Pairing of Oligonucleotides Containing N7-(2-Deoxy-β-D-erythro-pentofuranosyl)guanine (N7Gd)

The synthesis of oligonucleotides containing N⁷-(2-deoxy-β-D -erythro-pentofuranosyl)guanine (N⁷G_d; 1 ) is described. Compound 1 was prepared by nucleobase-anion glycosylation of 2-amino-6-methoxypurine ( 5 ) with 2-deoxy-3,5-di-O-(4-toluoyl)-α-D -erythro-pentofuranosyl chloride ( 6 ) followed by detoluoylation and displacement of the MeO group ( 8→10→1 ). Upon base protection with the (dimethylamino)methylidene residue (→ 11 ) the 4,4-dimethoxytrityl group was introduced at OH? C(5′) (→ 12 ). The phosphonate 3 and the phosphoramidite 4 were prepared and used in solid-phase oligonucleotide synthesis. The self-complementary dodecamer d(N⁷G? C)₆ shows sigmoidal melting. The T_m of the duplex is 40°. This demonstrates that guanine residues linked via N(7) of purine to the phosphodiester backbone are able to undergo base pairing with cytosine.     

Anion and Cavity Effects on the Complexation Behavior of Di-Aza-Benzo-Crown-Ether Calix[4]arene towards Zn(II) Ions

A novel compound, 25, 27 - N,N - di - ((2 -ethoxy)benzyl)butylenediamine - p - tert- butylcalix[4]arene, 1, has beensynthesized by reducing its Schiff base derivative. Inclusion studies by¹H-NMR spectroscopy in a mixed solvent (CD₃OD/CDCl₃) of25,27-N,N-di-((2-ethoxy)benzyl)propylenediamine-p-tert-butylcalix[4]arene,2, and 1 with Zn(II) ions, where counter anions are Cl^-, Br^-, I^- and NO ₃ ^- ,show that both ligands can bind Zn(II) to a different extent depending onthe counter anions and the cavity size of the ligands. The stabilityconstants of ZnX₂–1 (ZnX₂-2) complexes where X = Cl^-, Br^-, I^- and NO ₃ ^- are 1.4 ± 0.1 (1.6 ± 0.1), 1.7 ± 0.1 (1.9 ±0.1), 2.2 ± 0.1 (2.7 ± 0.1) and 4.7 ± 0.1 (6.0 ±0.1), respectively. The calix[4]arene unit of the ligand 2 was found to havea structural change from cone to partial cone conformation upon binding toZnCl₂, ZnBr₂ and ZnI₂.     

Extraction of99Mo-molybdophosphate and99mTc-pertechnetate from various acid solutions by bis/2-ethylhexyl/ phosphoric acid

The extractability of⁹⁹Mo-molybdophosphoric acid H₃/PMo₁₂O₄₀/ and^99mTc-pertechnetic acid /PTcO₄/ in 20% (v/v) bis /2-ethylhexyl/ phosphoric acid /HDEHP/ in benzene has been investigated at different concentrations of HCl, HBr and HNO₃ acids. The effect of extractant concentration and diluent on the extractability of molybdophosphoric and pertechnetic acids with 20% (v/v) HDEHP in benzene from different concentrations of HCl acid has also been studied.⁹⁹Mo-molybdo-phosphoric acid was found to be selectively extracted and separated from^99mTc-pertechnetic acid with 20% HDEHP in benzene at an acidity of about 0.49M HCl, HBr and HNO₃. The extractability of H₃/PMo₁₂O₄₀/ from these acids generally follows the decreasing order HBr>HCl>HNO₃. The separation factors /K_d molybdophosphoric/K_d pertechnetic/ were found to be 12.9×10⁵ and 7.6×10⁵ for HBr and HCl, respectively. The extractability of pertechnetic acid follows the order HCl>HBrHNO₃. Benzene is the diluent due to its radiation stability. A new procedure for the separation of^99mTc from⁹⁹Mo was suggested.     

Synthesis of A Novel Sialyl Lewis X Analogue Containing A Pyrrolidine in Place of N-Acetyl Glucosamine

ABSTRACT

The synthesis of the new sialyl Lewis X analogue, 4-O-(α-L-fucopyranosyl)-3-O-(3-O-sodium sulfonato-β-D-galactopyranosyl)-(2S,3R, 4R)-2-ethyl-3,4-dihydroxypyrrolidine 2 has been achieved. The N-acetyl glucosamine unit of natural Lewis X has been replaced by a rigid 3R/4R-dihydroxylated pyrrolidine 12. This one has been synthezised from the methyl 4-O-benzoyl-2,3-di-O-benzyl-6-deoxy-6-iodo-α-D-altropyranoside sugar precursor 10 using the Ganem/Bernotas one-pot elimination-reductive amination ring contraction reaction. The (2S, 3R, 4R)-1-benzyloxycarbonyl-3,4-dihydroxy-2-ethylpyrrolidine 12 obtained was subsequently regioselectively glycosylated, using 2,3,4-tri-O-benzyl-α-L-fucopyranosyl fluoride and 2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl bromide as glycosyl donors. Disaccharide containing pyrrolidine 21 was finally transformed into the target O-sulfated analog 2, after regioselective sulfation and usual deprotection.     

Base Hydrolysis of Pentaaminecobalt (III) Complexes: The [CoX(dien) (dapo)]n+ system. Part 3. The internal conjugate base mechanism

Azide anation and racemization of optically pure mer-exo(H)- and mer-endo(H)-[Co(OH)(dien)(dapo)]²⁺ ( A and B (X = OH), resp.; dien = N-(2-aminoethyl)ethane-1,2-diamine; dapo = 1,3-diaminopropan-2-ol) involve the same symmetrical pentacoordinate intermediate as the base hydrolyses of the corresponding mer-exo(H)- and mer-endo(H)-[CoX(dien)(dapo)]²⁺ species A and B , respectively, where X = Cl, Br, or N₃. The kinetic parameters of the anation process are fully compatible with the independently measured competition ratio. The rate data reveal that substitution of OH^? is unexpectedly fast, viz. it is not consistent with the usual sequence Br^? > Cl^? > H₂O > N > OH^?. This behavior is interpreted on the basis of an internal conjugate base mechanism which involves an amino-hydroxo/aminato-aqua tautomerism, viz. the reaction is actually an OH^? -catalyzed substitution of [CoH₂O(dien)(dapo)]³⁺ where deprotonation occurs effectively at the secondary-amine site NH of dien.     

Amide-based atropisomers in tachykinin NK1-receptor antagonists: synthesis and antagonistic activity of axially chiral N-benzylcarboxamide derivatives of 2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-one

A series of novel N-benzylcarboxamide derivatives of bicyclic compounds, 3,4-dihydropyrido[3,2-f][1,4]oxazepin-5(2H)-one and 2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-one, were synthesized by cyclization of N-benzyl-2-chloro-N-(2-hydroxyethyl)- [and -(3-hydroxypropyl)-] nicotinamides, respectively. Atropisomerism was observed in 5-[3,5-bis(trifluoromethyl)benzyl]-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3-b][1,5]oxazocin-6-ones due to steric hindrance of the carboxamide moiety and restriction of its rotation. Cyclization of N-[3,5-bis(trifluoromethyl)benzyl]-2-chloro-N-[(2S)-3-hydroxy-2-methylpropyl]-5-methyl-4-phenylnicotinamide gave (3S)-5-[3,5-bis(trifluoromethyl)benzyl]-3,8-dimethyl-7-phenyl-2,3,4,5-tetrahydro-6H-pyrido[2,3b][1,5]oxazocin-6-one, which exists predominantly in the thermodynamically stable aR-conformer in CDCl₃. This compound showed excellent NK₁-antagonistic activity with IC₅₀ value (in vitro inhibition of [¹²⁵I]-Bolton-Hunter-substance P binding in human IM-9 cells) of 0.47 nM, which is ca. 200-fold more potent than that of its enantiomer, indicating that the atropisomer chirality affects NK₁-receptor recognition.     

Reactions leading to the formation of O-3 on magnesium oxide

Ozonide ions were observed on MgO upon irradiation (254 nm) in the presence of O₂ at 25°C or upon reaction of O^-₂ on the surface with N₂O at 100°C. In the former case on O^-₂ intermediate is photodissociated to O and O^-. The latter subsequently reacts with O₂ forming O^-₃.     

Synthesis and DFT Defined trans (O5O6) Molecular Structure of Cs[Fe(1,3- pddadp )] · 2H2O. Strain Analysis and Spectral Assignment of the Complex

Summary. An iron(III) complex with the hexadentate ligand 1,3-propanediamine-N,N′-diacetate-N,N′-di-3-propionate (1,3-pddadp) was prepared, chromatographically isolated as its isomer trans(O₅O₆)-Cs[Fe(1,3-pddadp)] · 2H₂O, and characterized. The trans(O₅O₆) configuration of the iron(III) compound was found to dominate and this geometry was established by means of IR spectroscopy and Density Functional Theory (DFT). Structural data correlating the octahedral geometry of the [Fe(1,3-pddadp)]⁻ unit and an extensive strain analysis are discussed in relation to the information obtained for similar complexes. Antibacterial activities of the free ligand and its corresponding iron(III) complex towards common Gram-negative and Gram-positive bacteria are reported as well.     

Crystal Structures of 1,5,9,18,22,26-Hexaaza[11.11]-p-cyclophane Adducts; Two-dimensional Supramolecular Networks

Two newly identified supramolecular structures arise from self-assembly of the macrocyclic 1,5,9,18,22,26- hexaaza[11.11]-p-cyclophane salts with o-nitrophenol (C₂₈H₅₀N₆)⁴⁺·4(C₆H₄NO₂O)⁻ (1) and with HCl (C₂₈H₅₂N₆)⁶⁺·6Cl^-·4H₂O (2). In both cases two-dimensional supramolecular sheets are formed.     

Synthesis and characterization of the [Cu(Cin2bda)2]ClO4 and [Cu(Ncin2bda)2]ClO4 complexes: Crystal structure of [Cu(Ncin2bda)2]ClO4

Two copper(I) complexes [Cu(Cin₂bda)₂]ClO₄ (I) and [Cu(Ncin₂bda)₂]ClO₄ (II) have been prepared by the reaction of the ligands N²,N²′-bis(3-phenylallylidene)biphenyl-2,2′-diamine (L¹) and N²,N²′-bis[3-(2-nitrophenyl)allylidene]biphenyl-2,2′-diamine (L²) and copper(I) salt. These compounds were characterized by CHN analyses, ¹H NMR, IR, and UV-Vis spectroscopy. The C=N stretching frequency in the copper(I) complexes shows a shift to a lower frequency relative to the free ligand due to the coordination of the nitrogen atoms. The crystal and molecular structure of II was determined by X-ray single-crystal crystallography. The coordination polyhedron about the copper(I) center in the complex is best described as a distorted tetrahedron. A quasireversible redox behavior was observed for complexes I and II. The article is published in the original.     

Fluxional rearrangement in congested ruthenium(II) complexes containing pyrimidine- and/or pyridine-based dithioether ligands

The solvento species obtained by the treatment of cis-RuCl₂(N,N-L)₂ [L = di-2-pyridyl sulfide (dps), di-2-pyrimidyl sulfide (dprs)] with AgPF₆, reacted with dithioethers L′ [L′ = 2,6-bis(2-pyridylthiomethyl)pyridine (pytmp), 2,6-bis(2-pyrimidylthiomethyl)pyridine (prtmp) and 2,6-bis{2-(4-methyl)pyrimidylthiomethyl} pyridine (mprtmp)] to afford the compounds [Ru(N,N-L)₂(N,S-L′)][PF₆]₂. The ¹H NMR spectra indicate that L′ is chelated through S and N atoms with the formation of a four-membered ring. As a consequence, the ruthenium and sulfur atoms are stereogenic centers with ∆ and Λ and (R) and (S) configurations, respectively. NMR spectra, at low temperatures, show that two invertomers, of similar abundance, as enantiomeric couples ∆S, ΛR and ∆R, ΛS are present. In the methylene region, four AB systems are observed that in both the species contain two non-equivalent methylene groups. Variable-temperature NMR spectra and EXSY experiments show that the sulfur inversion produces an exchange between the invertomers. The one-dimensional band-shape analysis of the exchanging methylene signals showed that the energy barriers for the process are in the 43–52 kJ mol⁻¹ range. The possible mechanisms of the sulfur inversion are discussed.