Stereo-controlled approach to pyrrolidine iminosugar C-glycosides and 1,4-dideoxy-1,4-imino-l-allitol using a d-mannose-derived cyclic nitrone

Intramolecular N-alkylation of 2,3-O-isopropylidene-5-O-methanesulfonyl-6-O-t-butyldimethylsilyl-d-mannofuranose-oxime 7 afforded a five-membered cyclic nitrone 9, which on N-O bond reductive cleavage followed by deprotection of -OTBS and acetonide functionalities gave 1,4-dideoxy-1,4-imino-l-allitol (DIA) 3. Addition of allylmagnesium chloride to nitrone 9 afforded α-allylated product 10a in high diastereoselectivity providing an easy entry to N-hydroxy-C1-α-allyl-substituted pyrrolidine iminosugar 4a after removal of protecting group, while N-O bond reductive cleavage in 10a afforded C1-α-allyl-pyrrolidine iminosugar 4b.     

Stereo-controlled approach to pyrrolidine iminosugar C-glycosides and 1,4-dideoxy-1,4-imino-l-allitol using a d-mannose-derived cyclic nitrone

Intramolecular N-alkylation of 2,3-O-isopropylidene-5-O-methanesulfonyl-6-O-t-butyldimethylsilyl-d-mannofuranose-oxime 7 afforded a five-membered cyclic nitrone 9, which on N–O bond reductive cleavage followed by deprotection of –OTBS and acetonide functionalities gave 1,4-dideoxy-1,4-imino-l-allitol (DIA) 3. Addition of allylmagnesium chloride to nitrone 9 afforded α-allylated product 10a in high diastereoselectivity providing an easy entry to N-hydroxy-C1-α-allyl-substituted pyrrolidine iminosugar 4a after removal of protecting group, while N–O bond reductive cleavage in 10a afforded C1-α-allyl-pyrrolidine iminosugar 4b.     

An unexpected migration of O-silyl group under Mitsunobu reaction conditions

A 1,4 O→O silyl migration followed by nucleophilic substitution with phthalimide was observed under Mitsunobu reaction conditions. This one step secondary alcohol protection and primary alcohol substitution with N-nucleophiles was extended to a variety of 2-hydroxyethyl trialkylsilylether derivatives. A possible mechanism has been postulated based on the pK_a values of the alcohol and nucleophile. The present one-pot silyl migration and substitution reaction might find application in the stereoselective synthesis of novel iminosugar derived anti diabetic agents.     

A novel method for the formation of N-glycosides using hydroxamate

Direct formation of Asn-linked carbohydrate by N-glycosylation has been difficult, because of the lack of nucleophilicity of carboxamide nitrogen. We report here the novel N-glycosylation using Asn hydroxamate as a glycosyl acceptor. Reaction with glycosyl fluoride or glycosyl trichloroacetimidate afforded N-glycoside and subsequent reduction with SmI₂ gave Asn-linked glucose. Carbamate derived hydroxamates proved to have even enhanced reactivity to give N-glycosides in high yields.     

Syntheses of N-aryl-protected glucosamines and their stereoselectivity in chemical glycosylations

N-Aryl-protecting groups were introduced in glucosamines to achieve β-selective glycosylation. Various N-aryl aminosugars were synthesized via Buchwald–Hartwig reaction. Glycosylation using glycosyl trichloroacetimidates of N-aryl aminosugars smoothly proceeded in the presence of trimethylsilyl trifluoromethanesulfonate. Use of a glycosyl donor comprising an electron-donating 2,4-dimethoxyphenyl (DMP) group led to the glycosylation proceeding with high β selectivity. This stereoselectivity seemed to be derived from the formation of an aziridine intermediate. The DMP-protecting group can be removed immediately by using ammonium hexanitratocerate (IV).     

Efficient glycosylation with glycosyl ortho-allylbenzoates as donors

Glycosylation reactions are significant as they provide access to model compounds that are useful for elucidating biochemical pathways. Herein, we describe the development of glycosyl ortho-alkynylbenzoates as novel, bench-top stable, and readily available glycosyl donors. Glycosylation is promoted by inexpensive trimethylsilyl triflate (TMSOTf) in combination with N-iodosuccinimide (NIS) under mild reaction conditions; hence, the novel glycosyl donors are promising reagents for the synthesis of glycosides.     

Concise synthesis of two pentasaccharides corresponding to the α-chain oligosaccharides of Neisseria gonorrhoeae and Neisseria meningitidis

Two pentasaccharides containing a common tetrasaccharide (lacto-N-neotetraose) core, and d-galactosamine and N-acetyl neuraminic acid in the non-reducing ends, respectively, corresponding to the lipooligosaccharides of Neisseria gonorrhoeae and Neisseria meningitidis were synthesized in a very concise manner from a common trisaccharide derivative using minimum number of steps. Thioglycosides and glycosyl trichloroacetimidate have been used as glycosyl donors for glycosylations and yields were excellent in every step.     

Selective synthesis of fluorinated carbohydrates using N,N-diethyl-α,α-difluoro-(m-methylbenzyl)amine

Deoxyfluorination of a hydroxy group in carbohydrates was carried out using N,N-diethyl-α,α-difluoro-(m-methylbenzyl)amine. A primary hydroxy group in carbohydrates was effectively converted to the corresponding fluoride under microwave irradiation or at 100 °C. Deoxyfluorination of hydroxy groups at the anomeric position proceeded at below room temperature, and glycosyl fluorides could be obtained in good yields. The reaction chemoselectively proceeded, and various protecting groups of carbohydrates can survive under the reaction conditions.     

Synthesis of a tetrasaccharide related to the triterpenoid saponin isolated from Schima noronhae

A concise synthesis of a tetrasaccharide related to the cell-growth inhibitory triterpenoid saponin isolated from Schima noronhae is reported. A late stage 2,2,6,6-tetramethylpiperidinyloxy (TEMPO)-mediated oxidation of a primary hydroxyl group to carboxylic acid has been achieved under phase-transfer conditions. Stereoselective glycosylations were carried out using thioglycoside or glycosyl trichloroacetimidate activation using sulfuric acid immobilized on silica (H₂SO₄–silica) in conjunction with N-iodosuccinimide and alone, respectively.     

Iminosugar thioglycosides as glycosyl donors: a route to disaccharides with an iminosugar moiety

The iminosugar thioglycosides are used as glycosyl donors in glycosidation reactions. Thereby, iminosugar glycosides and disaccharide analogues with an iminosugar moiety are prepared. The yields are high and the method is stereoselective.     

Spectroscopic properties of meso-thienylporphyrins with different porphyrin cores

The absorption and fluorescence properties of a series of meso-thienylporphyrins with different porphyrin cores (N₄, N₃O, N₃S and N₂S₂ cores) were studied and compared with the corresponding meso-tetraarylporphyrins. The replacement of six-membered phenyl groups with five-membered thienyl groups at meso-positions resulted in red shifts and broadening of absorption and emission bands, low quantum yields and decreased S₁ state lifetimes and the maximum effects were observed for meso-tetrathienylporphyrin with N₂S₂ porphyrin core. Similar observations were noted for the dications of meso-thienylporphyrins compared to the dications of the corresponding meso-tetraarylporphyrins. These results suggest that the replacement of six-membered aryl group with five-membered thienyl groups at meso-positions, the electronic properties of the porphyrin were altered significantly.     

A new synthetic approach towards isoquinobenzazepinone and isoindolinobenzazepinone using acid-mediated cyclisation and Heck reaction

Six-membered ring cyclisation of N-ethylbenzazepinone, prepared from the condensation of benzazepinone with phenethyl iodide under basic conditions, smoothly provided the corresponding product, isoquino[1,2-b][3]benzazepinone, under acid-mediated conditions. On the other hand, the attempted direct five-membered ring cyclisation using the acid-mediated conditions failed to give the 7,5 fused ring isoindolinobenzazepinone from N-benzylbenzazepinone, but the 7,6 fused ring product was instead obtained. However, five-membered ring cyclisation of N-benzylbenzazepinone could be effected efficiently by employing the Heck reaction followed by catalytic hydrogenation to furnish the desired isoindolinobenzazepinone.     

Synthesis of novel glycosyl-1,2,3-1H-triazolyl methyl quinazolin-4(3H)-ones and their effect on GLUT4 translocation

Cu(OTf)₂ catalyzed synthesis of propargylated 2,3-dihydroquinazolin-4(1H)-ones has been accomplished from 2-amino-N-propargyl benzamides and aromatic aldehydes under MW irradiation. Next, a series of novel glycosyl triazolyl methyl quinazolin-4(3H)-ones have been synthesized by CuAAC reaction of propargylated 2,3-dihydroquinazolin-4(1H)-ones with glycosyl azides followed by iodine mediated oxidation. In this series, six compounds showed promising to significant GLUT4 translocation activity comparable to rosiglitazone.     

Study on comparison of reducing ability of three organic hydride compounds

Selective reduction of three kinds of substrates were studied to evaluate the reducing abilities of N,N-dimethyl-benzimidazolidine (DMBI), 2-phenylbenzimidazoline (PBI) and 2-phenylbenzothiazoline (PBT). As hydride donors, these three five-membered heterocyclic compounds performed different reducing abilities depending on the substrates.     

Photoswitching of an alcohol-sensitive photochromic diarylethene

The closed-ring isomer of diarylethene 1a, 1-(2-methyl-5-(4-N,N-diethylaminophenyl)thien-3-yl)-2-(2-methyl-5-phenylthien-3-yl)perfluorocyclopentene was found to cause the substitution reaction with primary alcohols at room temperature. The open-ring isomer 1a was stable in the alcohols. The product obtained in methanol was isolated by HPLC, and the structure was identified by ¹H NMR, mass spectrometry, and X-ray crystallographic analysis. It was revealed that two fluorine atoms were replaced with methoxy groups. The substitution reaction was also caused with ethylene glycol to form the five-membered ring. Both the products also showed photochromism, and had absorption maxima and photocycloreversion quantum yields different from those of 1a.     

Ring size and substituent steric effects in cyclic ketene-N,O/S-acetal trifluoroacetylations

Trifluoroacetylations of cyclic ketene-N,O/S-acetals exhibit a ring size effect. The five-membered rings 2,4,4-trimethyl-2-oxazoline, 2-methyl-2-oxazoline, and 2-methyl-2-thiazoline, each form cyclic ketene-N,O/S-acetal intermediates which then react with trifluoroacetic anhydride to give β-monotrifluoroacetylation products. Conversely, the six-membered ring 2-methyl-2-oxazine gives its β,β-bistrifluoroacetylation product. In situ-generated five-membered ring N-Me cyclic ketene-N,O-acetals, 3,4,4-trimethyl-2-methylene-oxazolidine, and 3-methyl-2-methylene-oxazolidine, and six-membered ring 3-methyl-2-methylene-1,3-oxazinane were each β,β-bistrifluoroacetylated. However, 3-methyl-2-methylene-oxazolidine also afforded a γ-lactam by an iodide-catalyzed rearrangement of its β,β-bistrifluoroacetylated derivative. In situ-generated 3-methyl-2-methylene-thiazolidine gives both β-mono- and β,β-bistrifluoroacetylation products and no lactam, in contrast to its N,O-analog 3-methyl-2-methyleneoxazolidine.     

C2-Acetamidomannosylation. Synthesis of 2-N-acetylamino-2-deoxy-α-d-mannopyranosides with glucal donors

A one-pot C2-acetamidomannosylation reaction for the synthesis of 2-N-acetylamino-2-deoxy-α-d-mannopyranosides from glucals is described. Glucal donors are activated by the reagent combination of 2,8-dimethyldibenzothiophene-5-oxide (DMDBTO) and trifluoromethanesulfonic anhydride. Upon subsequent addition of N-(TMS)acetamide and an appropriate glycosyl acceptor, the corresponding C2-acetamidomannopyranosides are formed.     

Synthesis and characterization of Cu,Ni and Zn binding capability of some amino- and imidazole hydroxamic acids: Effects of substitution of side chain amino-N for imidazole-N or hydroxamic-N-H for -N-CH3 on metal complexation

Solution equilibrium studies on Cu(II)-, Ni(II)- and Zn(II)-N-Me-β-Alaninehydroxamic acid (N-Me-β-Alaha), -N-Me-α-alaninehydroxamic acid (N-Me-α-Alaha), -Imidazole-4-carbohydroxamic acid (Im-4-Cha), -N-Me-imidazole-4-carbohydroxamic acid (N-Me-Im-4-Cha) and -Imidazole-4-acetohydroxamic acid (Im-4-Aha) systems have been performed by pH-potentiometry, UV–Vis spectrophotometry, EPR, CD, ESI-MS and ¹H NMR methods. According to the results: (i) the amino-N atoms are more basic in N-Me-α-Alaha and N-Me-β-Alaha than the hydroxamate function, but the trend is just the opposite between the imidazole-N(3) and hydroxamate. (ii) The metal ion anchor is always the hydroxamate part in the amino acid derivatives, while it is always the imidazole-N(3) in the studied imidazolehydroxamic acids. (iii) The three studied N-Me derivatives do not form metallacrowns. Only hydroxamate type chelate is formed with N-Me-β-Alaha, but with N-Me-α-Alaha a new type of coordination mode (via amino-N and hydroxamate-O) also exists. N-Me-Im-4-Cha also forms a dinuclear complex, [M₂L₃], with Cu(II) and Ni(II) (but not with Zn(II)). In this complex, one of the three ligands might bridge the two metal ions (five-membered hydroxamate-(O,O) plus five-membered (N_im, O_carb) bridging bis-chelating mode), while each of the additional two ligands binds to one metal. (iv) The two studied N–H derivatives, having dissociable proton on the hydroxamic-N, are able to form metallacrown species. A pentanuclear complex, [M₅L₄H₋₄], is exclusively formed above pH 4 between Cu(II) and Im-4-Aha. Interestingly, this 12-metallacrown-4 type complex, although together with various mononuclear binding isomers, appears also with Ni(II) and Zn(II). Unfortunately, the complexes of Im-4-Cha are not soluble in water at physiological pH at all.     

Copolymerization of N-vinylpyrrolidone with N-allylated acylhydrazines

The free-radical copolymerization of N-vinylpyrrolidone with N,N-diallyl-N′-acetylhydrazine and N,N-diallyl-N′-butanoylhydrazine has been investigated in bulk and solution. The copolymerization yields random copolymers enriched with N-vinylpyrrolidone units. The kinetic study of the reaction has revealed that the rate of copolymerization decreases with a rise in the fraction of an allyl monomer in the initial monomer mixture. Both double bonds of diallylacylhydrazines are involved in the copolymerization to give rise to five-membered pyrrolidine rings.     

Reactions of diphenyl- and diethylphosphinodithioic acids with <Emphasis Type="Italic">N</Emphasis>-alkyl-2-haloaldimines in the synthesis of new P,S- and N,P,S-containing organic compounds

Diphenyl- and diethylphosphinodithioic acids, unlike the stronger О,О-dialkyl phosphorodithioic acids, react with N-alkyl-2-chloroaldimines at a 1: 1 ratio, following two pathways: nucleophilic substitution of chlorine in the primary salt by the phosphinothioylthio group and reduction of the cation of the primary salt on the C–Cl bond. Nucleophilic substitution contributes more in the case of the stronger diphenylphosphinodithioic acid, as well as in the case of a large excess of the starting chlorimine. N-Alkyl-2-bromoaldimines react only by a single pathway, specifically, reducing the cation of the primary iminium salt on the C–Br bond. New iminium salts were synthesized and converted into the corresponding aldehydes and imines. The aldehydes synthesized were converted into acetals and five-membered heterocyclic compounds.