Synthesis and NMR characteristics of N‐acetyl‐4‐nitro,N‐acetyl‐5‐nitro,N‐acetyl‐6‐nitro and N‐acetyl‐7‐nitrotryptophan methyl esters

N‐acetyl‐4‐nitrotryptophan methyl ester (2), N‐acetyl‐5‐nitrotryptophan methyl ester (3), N‐acetyl‐6‐nitrotryptophan methyl ester (4) and N‐acetyl‐7‐nitrotryptophan methyl ester (5) were synthesized through a modified malonic ester reaction of the appropriate nitrogramine analogs followed by methylation with BF₃‐methanol. Assignments of the ¹H and ¹³C NMR chemical shifts were made using a combination of ¹H–¹H COSY, ¹H–¹³C HETCOR and ¹H–¹³C selective INEPT experiments. Copyright © 2008 Crown in the right of Canada. Published by John Wiley & Sons, Ltd     

Structure analysis of some α‐(n‐methyl‐n‐formylaminomethyl)‐quinolines

The ¹H and ¹³C nmr spectra of the rotational isomers 3a and 3b of 6‐N‐methyl‐N‐formylaminomefhyl)‐thioquinanthrene were completely assigned with a combination of 1D and 2D nmr techniques. The key‐parts of this methodology were long‐range proton‐carbon correlations and NOE experiments with N‐methyl‐N‐formylaminomethyl substituent. The X‐ray study of 4‐methyl‐2‐N‐methyl‐N‐formylaminomethyl)quinoline 4a as well as ¹H and ¹³C nmr spectra show that N‐methyl‐N‐formylaminomethyl substituent in 4a and 4b has a different steric arrangement than the same substituent in 3a and 3b .     

Transition metal complexes with pyrazole‐derived ligands. XI. [Zn(μ‐L)(HL)(OAc)]2 (HL is 4‐acetyl‐3‐amino‐5‐methyl­pyrazole)

The title compound, bis(μ‐4‐acetyl‐3‐amino‐5‐methyl­pyrazol­ato‐N¹:N²)­bis­[(acetato‐O)­(4‐acetyl‐3‐amino‐5‐methyl­pyraz­ole‐N²)­zinc(II)], [Zn₂(C₆H₈N₃O)₂(C₂H₃O₂)₂(C₆H₉N₃O)₂], ex‐ists as a centrosymmetric binuclear mol­ecule with two tetrahedrally coordinated Zn atoms bridged by two pyrazolate anions. The geometry of the terminal and bridging pyrazole ligands are slightly different as a consequence of their differing modes of coordination.     

An Improved Synthesis of 2‐Acetamido‐2‐deoxy‐ D‐gluconohydroximolactone (PUGNAc), A Strong Inhibitor of β‐N‐Acetylglucosaminidases

O‐(2‐Acetamido‐3,4,6‐tri‐O‐acetyl‐D ‐glucopyranosylidene)amino N‐phenylcarbamate ( 1 ), an established inhibitor of β‐N‐acetylglucosaminidases, has been prepared by an improved six‐step synthesis from N‐acetyl‐D ‐glucosamine.     

β‐1‐Acet­amido‐4‐O‐β‐d‐galacto­pyranosyl‐d‐gluco­pyran­ose dihydrate

The crystal structure of the title compound, C₁₄H₂₅NO₁₁·2H₂O, has been determined. The glucose and galactose residues are in a ⁴C₁ conformation. The N‐acetyl group has a Z‐anti conformation.     

Synthesis and Structure of O,O‐Diethyl N‐[(trans‐4‐Aryl‐5,5‐dimethyl‐2‐oxido‐2λ5‐1,3,2‐dioxaphosphorinan‐2‐yl)methyl]phosphoramidothioates

A study on the synthesis of the novel N‐(cyclic phosphonate)‐substituted phosphoramidothioates, i.e., O,O‐diethyl N‐[(trans‐4‐aryl‐5,5‐dimethyl‐2‐oxido‐2λ⁵‐1,3,2‐dioxaphosphorinan‐2‐yl)methyl]phosphoramidothioates 4a – l , from O,O‐diethyl phosphoramidothioate ( 1 ), a benzaldehyde or ketone 2 , and a 1,3,2‐dioxaphosphorinane 2‐oxide 3 was carried out (Scheme 1 and Table 1). Some of their stereoisomers were isolated, and their structure was established. The presence of acetyl chloride was essential for this reaction and accelerated the process of intramolecular dehydration of intermediate 5 forming the corresponding Schiff base 7 (Scheme 2).     

Novel ‘quinolone’ metal complexes: Synthesis and spectroscopic studies of mg(II), zn(II) and ba(II) complexes with N‐methyl (or NH)‐3‐acetyl‐4‐hydroxy quinolin‐2‐one ligands

The complexation between N‐methyl‐3‐acetyl‐4‐hydroxyquinolin‐2‐one (NMeQuin) and N‐H‐3‐acetyl‐4‐hydroxy quinolin‐2‐one (NHQuin) with MgCl₂, ZnCl₂ and BaCl₂ has been accomplished. The structure of the resulting complexes 1–5 has been elucidated through elemental analyses, FT‐IR and ¹H/¹³C NMR Spectroscopy and Mass Spectrometry. The spectroscopic data show complexes of the general formula Mg₂(OH)L₃(H₂O)_z and ML₂(H₂O)_Z where: M = Zn(II) and Ba(II), L = NMeQuin, NHQuin and z = 2, 4.     

Synthesis and Conformational Analysis of 1′‐ and 3′‐Substituted 2‐Deoxy‐2‐fluoro‐D‐ribofuranosyl Nucleosides

Convergent syntheses of the 9‐(3‐X‐2,3‐dideoxy‐2‐fluoro‐β‐D ‐ribofuranosyl)adenines 5 (X=N₃) and 7 (X=NH₂), as well as of their respective α‐anomers 6 and 8 , are described, using methyl 2‐azido‐5‐O‐benzoyl‐2,3‐dideoxy‐2‐fluoro‐β‐D ‐ribofuranoside ( 4 ) as glycosylating agent. Methyl 5‐O‐benzoyl‐2,3‐dideoxy‐2,3‐difluoro‐β‐D ‐ribofuranoside ( 12 ) was prepared starting from two precursors, and coupled with silylated N⁶‐benzoyladenine to afford, after deprotection, 2′,3′‐dideoxy‐2′,3′‐difluoroadenosine ( 13 ). Condensation of 1‐O‐acetyl‐3,5‐di‐O‐benzoyl‐2‐deoxy‐2‐fluoro‐β‐D ‐ribofuranose ( 14 ) with silylated N²‐palmitoylguanine gave, after chromatographic separation and deacylation, the N⁷‐β‐anomer 17 as the main product, along with 2′‐deoxy‐2′‐fluoroguanosine ( 15 ) and its N⁹‐α‐anomer 16 in a ratio of ca. 42 : 24 : 10. An in‐depth conformational analysis of a number of 2,3‐dideoxy‐2‐fluoro‐3‐X‐D ‐ribofuranosides (X=F, N₃, NH₂, H) as well as of purine and pyrimidine 2‐deoxy‐2‐fluoro‐D ‐ribofuranosyl nucleosides was performed using the PSEUROT (version 6.3) software in combination with NMR studies.     

Racemic and chiral 1‐[N‐(chloro­acetyl)carbamoylamino]‐2,3‐dihydro‐1H‐inden‐2‐yl chloroacetate

In the racemic crystals of (1S,2R)‐ or (1R,2S)‐1‐[N‐(chloro­acetyl)­carbamoyl­amino]‐2,3‐di­hydro‐1H‐inden‐2‐yl chloro­acetate, C₁₄H₁₄Cl₂N₂O₄, (I), the enantiomeric mol­ecules form a dimeric structure via the N—H?O cyclic hydrogen bond of the carbamoyl moieties. In the chiral crystals of (—)‐(1S,2R)‐1‐[N‐(chloro­acetyl)­carbamoyl­amino]‐2,3‐di­hydro‐1H‐inden‐2‐yl chloro­acetate, C₁₄H₁₄Cl₂N₂O₄, (II), the N—­H?O intermolecular hydrogen bond forms a zigzag chain around the twofold screw axis. The melting points and calculated densities of (I) and (II) are 446 and 396 K, and 1.481 and 1.445 Mg m^?3, respectively.     

Synthesis and Pairing Properties of Oligodeoxynucleotides Containing N7‐(Purin‐2‐amine Deoxynucleosides)

A general synthesis of the four isomeric N⁷‐α‐D ‐, N⁷‐β‐D ‐, N⁹‐α‐D ‐, and N⁹‐β‐D ‐(purin‐2‐amine deoxynucleoside phosphoramidite) building blocks for DNA synthesis is described (Scheme). The syntheses start with methyl 3′,5′‐di‐O‐acetyl‐2′‐deoxy‐D ‐ribofuranoside ( 2 ) as the sugar component and the N²‐acetyl‐protected 6‐chloropurin‐2‐amine 1 as the base precursor. N⁷‐Selectivity was achieved by kinetic control, and N⁹‐selectivity by thermodynamic control of the nucleosidation reaction. The two N⁷‐(purin‐2‐amine deoxynucleosides) were introduced into the center of a decamer DNA duplex, and their pairing preferences were analyzed by UV‐melting curves. Both the N⁷‐α‐D ‐ and N⁷‐β‐D ‐(purin‐2‐amine nucleotide) units preferentially pair with a guanine base within the Watson‐Crick pairing regime, with ΔT_ms of −6.7 and −8.7 K, respectively, relative to a C⋅G base pair (Fig. 3 and Table 1). Molecular modeling suggests that, in the former base pair, the purinamine base is rotated into the syn‐arrangement and is able to form three H‐bonds with O(6), N(1), and NH₂ of guanine, whereas in the latter base pair, both bases are in the anti‐arrangement with two H‐bonds between the N(3) and NH₂ of guanine, and NH₂ and N(1) of the purin‐2‐amine base (Fig. 4).     

Action of Hydrazines on 2‐(2‐Oxindolin‐3‐ylidene)malononitrile, (E,Z)‐Ethyl 2‐cyano‐2‐(2‐oxindolin‐3‐ylidene)acetate and Isatin‐β‐thiosemicarbazone as a Source of Spiro Indoline‐pyrazole Systems

2‐(2‐Oxindolin‐3‐ylidene)malononitrile ( 1a ) or (E,Z)‐ethyl 2‐cyano‐2‐(2‐oxindolin‐3‐ylidene)acetate ( 1b ) or isatin‐β‐thiosemicarbazone ( 1c ) undergoes reactions with prototype hydrazine hydrate itself and some of its simple congeners to give hydrazone derivatives bearing indoline‐2‐one moiety ( 2 ). The hydrazone derivatives ( 2 ) when heated with acetyl acetone or ethyl acetoacetate in dry pyridine afforded the spiro indoline derivatives ( 3a , 3b ). Also, cinnoline derivative ( 9 ) is obtained by action of hydrazine hydrate on the N‐acetyl derivative of ( 6a ). The structures of the newly synthesized compounds were evaluated by IR, ¹H‐NMR spectroscopy, mass spectra and elemental analyses.     

15N NMR spectra of some 3‐substituted 4(1H)‐quinolinones and their 1‐methyl derivatives

¹⁵N NMR spectral data for 3‐substituted (chloro, bromo, acetyl, carboxy, carboethoxy, methylsulfanyl, methylsulfinyl, N,N‐dimethylsulfamoyl, nitro) 4(1H)‐quinolinones and their 1‐methyl derivatives are presented. Copyright © 2003 John Wiley & Sons, Ltd.     

O‐Ethyl and O‐methyl N‐(2,3,4,6‐tetra‐O‐acetyl‐β‐d‐glucopyranosyl)thiocarbamate

In both the title structures, O‐ethyl N‐(2,3,4,6‐tetra‐O‐acetyl‐β‐d ‐gluco­pyran­osyl)­thio­carbam­ate, C₁₇H₂₅NO₁₀S, and O‐methyl N‐(2,3,4,6‐tetra‐O‐acetyl‐β‐d ‐gluco­pyran­osyl)­thiocar­bam­ate, C₁₆H₂₃NO₁₀S, the hexo­pyran­osyl ring adopts the ⁴C₁ conformation. All the ring substituents are in equatorial positions. The acetoxy­methyl group is in a gauche–gauche conformation. The S atom is in a synperi­planar conformation, while the C—N—C—O linkage is antiperiplanar. N—H?O intermolecular hydrogen bonds link the mol­ecules into infinite chains and these are connected by C—H?O interactions.     

Hydrogen‐bonding patterns in rac‐1‐acetyl‐5‐methyl‐2‐thioxoimidazolidin‐4‐one

In the title compound, C₆H₈N₂O₂S, also known as N‐acetyl‐2‐thiohydantoin–alanine, the molecules are joined by N—H...O hydrogen bonds, forming centrosymmetric R₂²(8) dimers; these dimers are linked by C—H...O interactions to form R₂²(10) rings, thus forming C₂²(10) chains that run along the [101] direction.     

Ammonium N‐acetyl‐l‐threoninate and methyl­ammonium N‐acetyl‐l‐threoninate

Ammonium N‐acetyl‐l ‐threoninate, NH₄⁺·C₆H₁₀NO₄^?, and methyl­ammonium N‐acetyl‐l ‐threoninate, CH₆N⁺·­C₆H₁₀NO₄^?, crystallize in the orthorhombic P2₁2₁2₁ and monoclinic P2₁ space groups, respectively. The two crystals present the same packing features consisting of infinite ribbons of screw‐related N‐acetyl‐l ‐threoninate anions linked together through pairs of hydrogen bonds. The cations interconnect neighbouring ribbons of anions involving all the nitrogen‐H atoms in three‐dimensional networks of hydrogen bonds. The hydrogen‐bond patterns include asymmetric `three‐centred' systems. In both structures, the Thr side chain is in the favoured (g^?g⁺) conformation.     

A Practical One‐Step Synthesis of 1,2‐Oxazoline Derivatives from Unprotected Sugars and Its Application to Chemoenzymatic β‐N‐Acetylglucosaminidation of Disialo‐oligosaccharide

A facile and practical method for synthesis of sugar oxazolines (=dihydrooxazoles) from the corresponding N‐acetyl‐2‐amino sugars has been developed by using 2‐chloro‐1,3‐dimethyl‐1H‐benzimidazol‐3‐ium chloride (CDMBI) as a dehydrative condensing agent. The intramolecular dehydrative reaction between the 2‐acetamido group and the anomeric OH group of unprotected N‐acetyl‐2‐amino sugars took place smoothly in H₂O, leading to the formation of a 1,2‐oxazoline (=4,5‐dihydrooxazole) moiety in good yield. Since the reaction proceeds in H₂O without using any protecting groups, the resulting oxazolines can be utilized as effective glycosyl donors for the subsequent enzymatic glycosylation. We have successfully demonstrated a highly efficient chemoenzymatic transglycosylation of a disialo‐oligosaccharide moiety to p‐nitrophenyl N‐acetylglucosaminide catalyzed by a mutant endo‐N‐acetylglucosaminidase without isolating disialo‐oligosaccharide oxazoline as synthetic intermediate.     

The α‐Glycosidation of Partially Unprotected N‐Acetyl and N‐Glycolyl Sialyl Donors in the Absence of a Nitrile Solvent Effect

The synthesis of α‐sialosides is one of the most difficult reactions in carbohydrate chemistry and is considered to be both a thermodynamically and kinetically disfavored process. The use of acetonitrile as a solvent is an effective solution for the α‐selective glycosidation of N‐acetyl sialic acids. In this report, we report on the α‐glycosidation of partially unprotected N‐acetyl and N‐glycolyl donors in the absence of a nitrile solvent effect. The 9‐O‐benzyl‐N‐acetylthiosialoside underwent glycosidation in CH₂Cl₂ with a good α‐selectivity. On the other hand, the 4,7,8‐O‐triacetyl‐9‐O‐benzyl‐N‐acetylthiosialoside was converted to β‐sialoside as a major product under the same reaction conditions. The results indicate that the O‐acetyl protection of the sialyl donor was a major factor in reducing the α‐selectivity of sialylation. After tuning of the protecting groups of the hydroxy groups at the 4,7,8 position on the sialyl donor, we found that the 9‐O‐benzyl‐4‐O‐chloroacetyl‐N‐acetylthiosialoside underwent sialylation with excellent α‐selectivity in CH₂Cl₂. To demonstrate the utility of the method, straightforward synthesis of α(2,9) disialosides containing N‐acetyl and/or N‐glycolyl groups was achieved by using the two N‐acetyl and N‐glycolyl sialyl donors.     

Probing the Conformational Changes in the Enzymatic Hydrolysis of 2‐Acetamido‐2‐deoxy‐β‐D‐glucopyranosides

The isoquinuclidines 7 and 8 were synthesised and tested as inhibitors of hexosaminidases from jack beans and from bovine kidney. These isoquinuclidines mimick the ^1,4B‐conformer of a N‐acetyl‐glucosamine‐derived β‐d‐ glucopyranoside; they are competitive inhibitors with K_i values from 0.014 to 0.30 μM . The strong inhibition of these enzymes agrees with the hypothesis that the enzymatic hydrolysis of 2‐acetamido‐2‐deoxy‐β‐d‐ glucopyranosides proceeds via a boat‐like conformer with a pseudo‐axial scissile glycosidic bond and a pseudo‐axial acetamido substituent optimally oriented to effect an intramolecular substitution of the aglycon.     

Synthesis and Evaluation of Novel 5‐cyclohexyl‐2‐(4″‐substitutedphenyl)‐3‐(2″‐substitutedphenyl)4H‐2,3,3a,5,6,6a‐hexahydropyrrolo[3,4‐d]isoxazole‐4,6‐dione Derivatives for Their In Vitro Antioxidant and Antibacterial Activities

1,3‐Dipolar cycloaddition reactions of N‐cyclohexyl maleimide ( 1 ) with azomethine N‐oxide ( 2 ) have afforded novel isoxazolidine ( 3 ) in excellent yield. Their structures have been characterized from their IR, ¹H‐NMR, ¹³C‐NMR, ¹H,¹H‐COSY, MS(ESI), and elemental analysis techniques. In vitro antibacterial activity of the synthesized compounds were investigated against a representative panel of pathogenic strains specifically two Gram‐positive bacteria (Staphylococcus aureus and Streptococcus pyogenes ) and two Gram‐negative bacteria (Pseudomonas aeruginosa and Escherichia coli ) using agar‐well diffusion assay. Some of the compounds ( 3a , 3k , 3n , and 3o ) exhibited promising antibacterial activities. All the synthesized compounds have also been screened for their antioxidant activities and were found to be significantly active.     

Ethyl N‐[2‐(hydroxy­acetyl)­phenyl]­carbamate,ethyl N‐[2‐(hydroxy­acetyl)‐4‐iodo­phenyl]­carbamate and ethyl N‐[2‐(hydroxy­acetyl)‐4‐methyl­phenyl]­carbamate

In ethyl N‐[2‐(hydroxy­acetyl)phenyl]carbamate, C₁₁H₁₃NO₄, all of the non‐H atoms lie on a mirror plane in the space group Pnma; the mol­ecules are linked into simple chains by a single C—H⋯O hydrogen bond. The mol­ecules of ethyl N‐[2‐(hydroxy­acetyl)‐4‐iodo­phenyl]carbamate, C₁₁H₁₂INO₄, are linked into sheets by a combination of O—H⋯I and C—H⋯O hydrogen bonds and a dipolar I⋯O contact. Ethyl N‐­[2‐(hydroxy­acetyl)‐4‐methyl­phenyl]carbamate, C₁₂H₁₅NO₄, crystallizes with Z′ = 2 in the space group P; pairs of mol­ecules are weakly linked by an O—H⋯O hydrogen bond and these aggregates are linked into chains by two independent aromatic π–π stacking inter­actions.