SYNTHESIS OF NEW OXAMIDE DERIVATIVES OF D-GLUCOSAMINE AND ALIPHATIC OR AROMATIC AMINES

New oxamides, derivatives of D-glucosamine and aliphatic or aromatic amines were prepared by acylation of methyl 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-α- or -β-D-glucopyranoside (1c or 1d) with oxalyl chloride, followed by reaction with amine. The reaction was assumed to proceed by the intermediate of N-carbomethoxy N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-α or β-D-glucopyranosid-2-yl) oxamic acid chloride which reacted with amines, and afforded N-acetyl, N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-α- or -β-D-glucopyranosid-2-yl), N′-alkyl or aryloxamide (5–7), and N-(methyl 3,4,6-tri-O-acetyl-2-deoxy-α- or -β-D-glucopyranosid-2-yl), N′-alkyl or aryloxamide (8–13).     

Syntheses of l-glucosamine donors for 1,2-trans-glycosylation reactions

Two new l-glucosamine donors, that is pent-4-enyl 3,4,6-tri-O-acetyl-2-allyloxycarbonylamino-2-deoxy-β-l-glucopyranoside 16 and ethyl 3,4,6-tri-O-acetyl-2-allyloxycarbonylamino-2-deoxy-1-thio-β-l-glucopyranoside 21 were prepared in 12 steps from l-arabinose. The reaction pathway uses 3,4,6-tri-O-acetyl-l-glucal 5, and then 3,4,6-tri-O-acetyl-2-deoxy-2-iodo-α-l-mannopyranosyl azide 8 as intermediates. The latter, together with donors 16 and 21, were used for preparing l-glucosamine neoglycolipids.     

4-alkylated 2-(2,3,5-tri-<Emphasis Type="Italic">O</Emphasis>-acyl-β-D-ribofuranosyl)- and 2-(2,3,4,6-tetra-<Emphasis Type="Italic">O</Emphasis>-acetyl-β-D-glucopyranosyl)-1,2,4-triazine-3,5-diones

The alkylation of 2-(2,3,5-tri-O-acyl-β-D-ribofuranosyl)- and 2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)- 1,2,4-triazine-3,5-diones with benzyl halides afforded the corresponding 4-benzyl derivatives whose structure was determined by spectral methods, including X-ray analysis. Some of the synthesized compounds were tested for antibacterial and antitumor activity.     

Synthesis Of Ligands Related To The O-Specific Antigen Of Shigella Dysenteriae Type 1.

Abstract

Stereoselective α-D-galactosylation at the position 3 of 4,6-O-substituted derivatives of methyl 2-acetamido-2-deoxy-α-D-glucopyranoside is described. Glycosyl chlorides derived from 3,4,6-tri-O-acetyl-2-O-benzyl- and 2-O-(4-methoxybenzyl)-D-galactopyranose have been used as glycosyl donors. Methyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-3-O-(3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-α-D-glucopyranoside (27) and methyl 2-acetamido-4,6-di-O-benzyl-2-deoxy-3-O-(3,4,6-tri-O-acetyl-α-D-galactopyranosyl)-α-D-glucopyranoside (31) have been prepared.     

Synthesis of 6-S-(5-Acetamido-3,5-Dideoxy-D-Glycero-α-D-Galacto-2-Nonulopyranosylonic Acid)-6-Thio-Hexopyranosides

The reaction of the sodium salt of methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D-glycero-α-D-galacto-2-nonulo-pyranosonate with a variety of 6-bromo-6-deoxy-D-hexopyranosides, such as methyl 2,3,4-tri-O-acetyl-6-bromo-6-deoxy-α-D-glucopyranos-ide, -galactopyranoside, allyl 2,3,4-tri-O-acetyl-6-bromo-6-deoxy-β-D-glucopyranoside, and allyl 2-acetamido-3,4-di-O-acetyl-6-bromo-2,6-dideoxy-β-D-glucopyranoside, gave the corresponding (2→6)-linked disaccharides, α-glycosides of 2-thio-N-acetylneuraminic acid derivative in good yields. These disaccharides were converted, via O-deacetylation, followed by hydrolytic removal of the ester group, into the title compounds.     

Synthesis of (2<Emphasis Type="Italic">S</Emphasis>,3<Emphasis Type="Italic">S</Emphasis>,4<Emphasis Type="Italic">S</Emphasis>)-2,3-<Emphasis Type="Italic">O</Emphasis>-isopropylidene-4-(methoxycarbonylmethyl)cyclopentan-1-one

(2S,3S,4S)-2,3-O-Isopropylidene-4-(methoxycarbonylmethyl)cyclopentan-1-one was synthesized starting from D-ribose through methyl (Z)-3-(5-acetyl-2,2-acetoxyacetyl-2,2-dimethyl-1,3-dioxolan-4-yl)prop-2-enoate which was subjected to cyclization in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene, followed by decarboxylation.     

Synthesis and characterization of new acyclic nucleosides analogues derived from 2-phenyl quinoline candidates

Reaction of 4-substituted quinoline hydrazide with some aldohexoses and aldopentoses gave a series of new N-β-glycosides. The following cyclization of N-β-glycosides with acetic anhydride led to O-acetyl-[5-(2-phenylquinolin-4-yl)-1,3,4-oxadiazol-2-yl]-D-glycosides. Structure of the newly synthesized products was elucidated by chemical and spectroscopic methods.     

Stereoselective Glycosidic Coupling Reactions of Fully Benzylated 1,2-Anhydro Sugars with N-Tosyl- or N-Benzyloxycarbonyl-l-serine Methyl Ester

Abstract

The glycosidic coupling reaction of 1,2-anhydro-3,4,6-tri-O-benzyl-β-d-mannopyranose (7), 1,2-anhydro-3,4,6-tri-O-benzyl-α-d-galactopyranose (21), and 1,2-anhydro-3,4-di-O-benzyl-α-d-xylopyranose (18) with N-tosyl- (10) or N-benzyloxycarbonyl- (11) L-serine methyl ester provides a new stereocontrolled synthesis of 1,2-trans linked glycopeptides. The 1,2-anhydro sugars are shown to react smoothyl with 10 or 11 in the presence of Lewis acid (ZnCl₂ or AgOTf) as well as powdered 4A molecular sieves in CH₂Cl₂ at room temperature to afford glycosyl serine derivatives with high stereoselectivity and high yield in less than 30 min. An improved method using 2-O-acetyl-3,4,6-tri-O-benzyl-α-d-mannopyranosyl chloride (6) as the key intermediate for ring closure was applied for the synthesis of 1,2-anhydro-3,4,6-tri-O-benzyl-β-d-mannopyranose.     

Glucose ferrocenyl-oxazolines: Coordination behavior toward [Pd(η-allyl)Cl]2 studied by ESI-MS

Several new oxazolin-2-yl-substituted ferrocenes based on 2-amino-2-deoxy-α-d-glucose were synthesized via the corresponding amides followed by closing the oxazoline-ring with SnCl₄.Coordination properties of representatives of the group of mono- and bis-oxazolinyl ferrocenes, 2-ferrocenyl-4,5-(3,4,6-tri-O-acetyl-1,2-dideoxy-d-glucopyrano)-[2,1-d]-oxazoline and 1,1′-bis{4,5-(3,4,6-tri-O-acetyl-1,2-dideoxy-d-glucopyrano)-[2,1-d]-oxazolin-2-yl}ferrocene, respectively, toward [Pd(η³-allyl)Cl]₂ were investigated by electrospray ionization mass spectrometry in positive ion mode and by MS/MS technique.With the monooxazoline derivative mainly a 1:1 complex with the Pd-moiety was found in the mass spectrum while the bisoxazoline yields a stoichiometry of 2:1 (oxazoline:Pd). The latter result is attributed to steric hindrance of the coordination of a second Pd-moiety to the bulky bisoxazolinyl-ferrocene.In the case of 1,1′-bis{4,5-(3,4,6-tri-O-acetyl-1,2-dideoxy-d-glucopyrano)-[2,1-d]-oxazolin-2-yl}ferrocene 9 overlapping of two signals in the m/z range from 955-965 was found which can be assigned to the singly charged adduct [C₃₆H₄₀FeN₂O₁₆ + Pd(η³-C₃H₅)]⁺ and a doubly charged Pd-ligand cluster with the general formula Pd₂[L(9)]₂.In addition, the molecular structure of 1,1′-bis{4,5-(3,4,6-tri-O-acetyl-1,2-dideoxy-d-glucopyrano)-[2,1-d]-oxazolin-2-yl}ferrocene was determined by X-ray diffraction analysis.     

Alkylation of 2-(methylsulfanyl)-6-polyfluoroalkylpyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones with haloalkanes

The alkylation of ambident anions of 2-(methylsulfanyl)-6-(polyfluoroalkyl)pyrimidin-4(3H)-ones with 4-bromobutyl acetate leads to concurrent formation of O- and N-(4-acetoxybutyl) derivatives. Polar aprotic solvents favor formation of the O-isomer, and weakly polar dioxane favors N-alkylation. The reaction of 2-(methylsulfanyl)-6-(trifluoromethyl)pyrimidin-4(3H)-one with an equimolar amount of 1,2-dibromoethane in polar acetonitrile gives a mixture of N,N-, O,O-, and N,O-bridged bis-pyrimidines, as well as N- and O-[2-(methylsulfanyl)ethyl] derivatives, whereas in the presence of 10 equiv of 1,2-dibromoethane the N,O-isomer is formed as the only product. The reaction in weakly polar tetrahydrofuran yields N,N- and N,O-bispyrimidines.     

SYNTHESIS OF A MANNOTETRAOSE—THE REPEATING UNIT OF THE CELL-WALL MANNANS OF MICROSPORUM GYPSEUM AND RELATED SPECIES OF TRYCHOPHYTON

A tetrasaccharide, α-D-mannopyranosyl-(1→2)-α-D-mannopyranosyl-(1→6)-α-D-mannopyranosyl-(1→6)-D-mannopyranose (1), the repeating unit of the cell-wall mannans of Microsporum gypseum and related species of Trychophyton, was synthesized using 6-O-acetyl-2,3,4-tri-O-benzoyl-α-D-mannopyranosyl trichloroacetimidate (5) and 2-O-acetyl-3,4,6-tri-O-benzoyl-α-D-mannopyranosyl trichloroacetimidate (13) as the glycosyl donors in “the inverse Schmidt” procedure.     

Synthesis,structure, and antimicrobial activity of methyl (4-alkanoyl-1,5-diaryl-2-hydroxy-3-oxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-pyrrol-2-yl)acetates

Reactions of methyl 3,4,6-trioxoalkanoates (3,4-dihydroxy-6-oxo-2,4-alkadienoates) with mixtures of aromatic aldehydes and arylamines or with the corresponding N-(arylmethylidene)anilines afforded methyl (4-alkanoyl-1,5-diaryl-2-hydroxy-3-oxo-2,3-dihydro-1H-pyrrol-2-yl)acetates. The product structure was discussed on the basis of their IR, ¹H NMR, and mass spectra and X-ray diffraction data, and their antimicrobial activity against Staphylococcus aureus P-209 and Escherichia coli M₁₇ was evaluated.     

2-amino-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]pyrimidines: Synthesis and reactions with electrophilic reagents

The hydrogenation of 2-amino-5-R-7-R′-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidines with NaBH₄ led to the formation of 2-amino-5-R-7-R′-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]pyrimidines. Acylation, sulfonylation, and alkylation of these compounds depending on conditions and the reagent character occur at the amino group, atoms N³ or N⁴. The treatment with alkali of 2-amino-3-benzyl-5-R-7-R′-4,5,6,7-tetrahydro-1,2,4-triazolo-[1,5-a]pyrimidinium bromide resulted in 2-amino-3-benzyl-5-R-7-R′-3,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]-pyrimidine, similar reaction of 2-acetamido-3-benzyl-5-R-7-R′-4,5,6,7-tetrahydro-1,2,4-triazolo[1,5-a]-pyrimidinium bromide gave a mesoionic product of a hydrogen elimination from the amide nitrogen atom.     

Efficient total syntheses of natural pterin glycosides: limipterin and tepidopterin

The key, versatile precursors N²-(N,N-dimethylaminomethylene)-1′-O-(4-methoxybenzyl)-3-[2-(4-nitrophenyl)ethyl]biopterin (29a) and its ciliapterin analog (29b) were prepared, respectively, from d-xylose (in 14 steps) and l-xylose (in 11 steps). Treatment of 29a and 29b with 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl bromide in the presence of silver triflate and tetramethylurea, followed by removal of the protecting groups, led to the first selective syntheses of limipterin (3) and tepidopterin (5), respectively.     

Crystal structures of a family of layered coordination polymers containing divalent metal ions (Mn<Superscript>2+</Superscript>, Co<Superscript>2+</Superscript>, Ni<Superscript>2+</Superscript> and Zn<Superscript>2+</Superscript>) and the 3-amino 4-methyl benzoate ion

The syntheses and crystal structures of the layered coordination polymers M(C₈H₈NO₂)₂ [M = Mn (1), Co (2), Ni (3) and Zn (4)] are described. These isostructural compounds contain centrosymmetric trans-MN₂O₄ octahedra as parts of infinite sheets; the ligand bonds to three adjacent metal ions in μ³-N,O,O′ mode from both its carboxylate O atoms and its amine N atom. In each case, weak intra-sheet N–H?O and C–H?O hydrogen bonds may help to consolidate the structure. Crystal data: 1, C₁₆H₁₆MnN₂O₄, M _r = 355.25, monoclinic, P2₁/c (No. 14), a = 10.6534(2) Å, b = 4.3990(1) Å, c = 15.5733(5) Å, β = 95.1827(10)°, V = 726.85(3) ų, Z = 2, R(F) = 0.026, wR(F ²) = 0.067. 2, C₁₆H₁₆CoN₂O₄, M _r = 359.24, monoclinic, P2₁/c (No. 14), a = 10.6131(10) Å, b = 4.3374(4) Å, c = 15.3556(17) Å, β = 95.473(4)°, V = 703.65(12) ų, Z = 2, R(F) = 0.041, wR(F ²) = 0.091. 3, C₁₆H₁₆N₂NiO₄, M _r = 359.02, monoclinic, P2₁/c (No. 14), a = 10.6374(4) Å, b = 4.2964(2) Å, c = 15.2827(8) Å, β = 95.9744(14)°, V = 694.66(6) ų, Z = 2, R(F) = 0.028, wR(F ²) = 0.070. 4, C₁₆H₁₆N₂O₄Zn, M _r = 365.68, monoclinic, P2₁/c (No. 14), a = 10.6385(5) Å, b = 4.2967(3) Å, c = 15.2844(8) Å, β = 95.941(3)°, V = 694.89(7) ų, Z = 2, R(F) = 0.038, wR(F ²) = 0.107.     

Reactions of <Emphasis Type="Italic">N</Emphasis>-acetyl- and <Emphasis Type="Italic">N</Emphasis>-ethoxycarbonyl-2-(1-cycloalken-1-yl)anilines with <Emphasis Type="Italic">meta</Emphasis>-cloroperbenzoic acid

Reaction of N-ethoxycarbonyl-2-(1-cycloalken-1-yl)anilines with meta-cloroperbenzoic acid leads to the corresponding 2-[1-o-(3-chlorobenzoyl)-2-hydroxycyclopent-1-yl]anilines. 5-(2-Acetylaminophenyl)-5-oxopentanic or 6-oxohexanic acids are formed as main products in the reaction of N-acetyl-2-(1-cycloalken-1-yl)anilines with m-chloroperbenzoic acid in CH₂Cl₂. N-Acetyl-2-(1-cyclopenten-1-yl)-3,6-dimethylaniline is an exception in this series since its reaction stops at the stage of epoxide formation.     

Synthetic Mucin Fragments: Methyl-3-O-(2-Acetamido-2-Deoxy-4-O- and 6-O-β-D-Galactopyranosyl-β-D-Glucopyranosyl)-β-D-Galactopyranoside and Methyl 3-O-(2-Acetamido-2-Deoxy-4-O- and 3-O-Methyl-β-D-Glucopyranosyl-3-D-Galactopyranoside

Abstract

Glycosylation of methyl 3-O-(2-acetamido-3, 6-di-O-benzyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (2) with 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide (1), catalyzed by mercuric cyanide, afforded a trisaccharide derivative, which was not separated, but directly O-deacetylated to give methyl 3-O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-β-D-galactopyranosyl-β-D-giucopyranosyl)-2,4,6-tri-O-benzyl-β-D-galactopyranoside (8). Hydrogenolysls of the benzyl groups of 8 then furnished the title trisaccharide (9). A similar pflyccsylation of methyl 3-O-(2-acetamido-3-O-acetyl-2-deoxy-β-D-glucopyranosyl)-2,4,6-tri-O-benzyl- β-D-galactopyranoside (obtained by acetylation of 4, followed by hydrolysis of the benzylidene acetal group) with bromide 1 gave a tribenzyl trisaccharide, which, on catalytic hydrogenolysls, furnished the isomeric trisaccharide (12). Methylation of 4 and 2 with methyl iodide-silver oxide in 1:1 dichloro-methane-N, N-dimethylformamide gave the 3-O- and 4-O-monomethyl ethers (13) and (15), respectively. Hydrogenolysis of the benzyl groups of 13 and 15 then provided the title monomethylated disaechartdes (15) and (16), respectively. The structures of trisacchacides 9 and 12, and disaccharides 14 and 16 were all established by ¹³C MMR spectroscopy.     

The anomeric Pudovik rearrangement

The O,O-dibenzyl-S-glycosyl phosphothioite derived from 3,4,6-tri-O-acetyl-2-acetamido-2-deoxy-1-thio-α-d-glucopyranose rearranges under the influence of triethylborane and air to provide the corresponding 1-C-pyranosyl-O,O-dibenzylphosphonothioate, a new type of carbohydrate derivative. The isomeric beta phosphothioite is compared, and evidence of a radical chain mechanism for the Pudovik rearrangement is presented.     

Sm<Subscript>2</Subscript>S<Subscript>3</Subscript>-Sm<Subscript>2</Subscript>O<Subscript>3</Subscript> phase diagram

The Sm₂S₃-Sm₂O₃ phase diagram was studied by physicochemical methods of analysis from 800 K up to melting. Two oxysulfides are formed in the system: Sm₁₀S₁₄O with tetragonal crystal structure (space group I41/acd; unit cell parameters: a = 1.4860 nm, c = 1.9740 nm; microhardness: H = 4700 MPa; solid decomposition temperature: 1500 K) and Sm₂O₂S with hexagonal structure (space group P-3m1; a = 0.3893 nm, c = 0.6717 nm; H = 4500 MPa; congruent melting temperature: 2370 K). Within the extent of the Sm₂O₂S-based solid solution (61–70 mol % Sm₂O₃) at 1070 K, a singular point appears at the compound composition on property-composition curves. The eutectic coordinates: 23 mol % Sm₂O₃ and 1850 K; 80 mol % Sm₂O₃ and 2290 K.     

Synthesis of flavonoid 2-deoxyglucosides via the Mitsunobu reaction

The Mitsunobu reaction of flavonoids and 3,4,6-tri-O-acetyl-2-deoxy-d-glucopyranose or 3,4,6-tri-O-benzyl-2-deoxy-d-glucopyranose is a very effective method for the stereoselective synthesis of flavonoid 2-deoxyglucosides. Since there is no C2 substituent on the sugar moieties, the observed α- or β-stereoselectivity was mainly controlled by the (acetyl or benzyl) protecting groups. Possible mechanistic insights are offered to explain the dual stereoselectivity.