Ein einfacher Zugang zu 4-hydroxy-2,5-dimethyl-3(2H)-furanon (furaneol), einem Aromabestandteil von Ananas und Erdbeere

Furaneol®

1 Registered trade mark of Firmenich SA.

[4-hydroxy-2,5-dimethyl-3(2H)-furanone ( 1 )], a flavour component of pineapple and strawberry, has been prepared by a two-step synthesis starting with readily available 3-hexyne-2,5-diol. By the same method 4-hydroxy-5-methyl-3(2H)-furanone ( 2 ) and 2-ethyl-4-hydroxy-5-methyl-3(2H)-furanone ( 3a ) have been prepared from 2-pentyne-1,4-diol and 3-heptyne-2,5-diol, respectively.     

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.     

New triterpenoid glycosides fromThalictrum minus L.

Two triterpenoid diglycosides of the cycloartane series were isolated from the terrestrial part ofThalictrum minus L. (Ranunculaceae). Genins of these glycosides are side-chain structural isomers—3-O-β-d-galactopyranosyl-29-O-β-d-glucopyranosyl-9β, 19-cyclo-20(S)-lanost-24(Z)-ene-3β, 16β, 22(S), 26, 29-pentaol and 3-O-β-d-galactopyranosyl-29-O-β-d-glucopyranosyl-9β, 19-cyclo-20(S)-lanost-25-ene-3β, 16β,22(S), 24ζ, 29-pentaol. The structures of these glycosides were established using 1D and 2D NMR spectroscopy and FAB mass spectrometry. For Part 9, see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1434–1437, July, 1998.     

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     

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.     

Synthesis of oligosaccharides related to the HNK-1 antigen. 5. Synthesis of a sulfo-mimetic of the HNK-1 antigenic trisaccharide

2-Aminoethyl 3,6-di-O-sulfo-β-D-glucopyranosyl-(1→3)-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-β-D-glucopyranoside, which is the sulfo-mimetic of the antigenic trisaccharide HNK-1, and the corresponding monosulfates, viz., 2-aminoethyl 3-O-sulfo-and 2-aminoethyl 6-O-sulfo-β-D-glucopyranosyl-(1→3)-β-D-galactopyranosyl-(1→ 4)-2-acetamido-2-deoxy-β-D-glucopyranosides, were synthesized. 2-Azidoethyl 2,4-di-O-benzoyl-β-D-glucopyranosyl-(1→3)-2,4,6-tri-O-benzoyl-β-D-galactopyranosyl-(1→ 4)-2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside served as the common precursor for the sulfated trisaccharides. This compound was synthesized according to the [2+1] pattern from monosaccharidic precursors: 3,6-di-O-acetyl-2,4-di-O-benzoyl-D-glucopyranosyl trichloroacetimidate, allyl 2-O-benzoyl-4,6-O-benzylidene-β-D-galactopyranoside, and 2-azidoethyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-β-D-glucopyranoside. The structures of the glycosyl donors and glycosylation conditions were optimized for the efficient synthesis of the glucosyl-β-(1→3)-galactose disaccharide block and its subsequent transformation into the target trisaccharide sequence. Dedicated to Academician V. A. Tartakovsky on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1593–1607, August, 2007.     

Determination and Pharmacokinetic Study of Calycosin-7-O-β-d-glucoside in Rat Plasma After Intravenous Administration of Aidi Lyophilizer

Aidi injection is a clinical medicine used in China for the treatment of cancer. Calycosin-7-O-β-d-glucoside is the main effective components of the formulas. In this study, a high performance liquid chromatographic (LC) method was developed to quantify calycosin-7-O-β-d-glucoside in rat plasma using a liquid–liquid extraction and ultraviolet (UV) absorbance detection. LC analysis was performed on a Diamonsil C₁₈ column (200 × 4.6 mm i.d., 5 μm particle size) with isocratic mobile phase consisting of acetonitrile–0.05% phosphoric acid (19.5:80.5, v/v) of a flow rate of 1.0 mL min⁻¹. The linear range was 0.11–17.6 μg mL⁻¹ and the low quantification limit was 0.11 μg mL⁻¹ (S/N = 10). The intra- and inter-day relative standard deviations (RSD) in the measurement of quality control (QC) samples 0.11, 0.22, 1.32 and 8.80 μg mL⁻¹ ranged from 4.1 to 6.3 and 4.3 to 6.2%, respectively. The accuracy was from −6.7 to 4.3% in terms of relative error (RE). Calycosin-7-O-β-d-glucoside was stable in storage at −20 °C for 2 weeks and stable after three freeze–thaw cycles in rat plasma. This method was validated for specificity, accuracy, precision and was successfully applied to pharmacokinetic study of calycosin-7-O-β-d-glucoside in rat plasma after intravenous administration of Aidi lyophilizer.     

Minor asterosaponin archasteroside C from the starfish <Emphasis Type="Italic">Archaster typicus</Emphasis>

A new minor asterosaponin (20S)-6-O-{β-d-fucopyranosyl-(1→2)-[β-d-fucopyranosyl-(1→4)-β-d-quinovopyranosyl-(1→2)]-β-d-quinovopyranosyl-(1→3)-β-d-quinovopyranosyl}-3β,6α,20-trihydroxycholest-9(11)-en-23-one 3-sulfate (archasteroside C) was isolated from the starfish Archaster typicus collected in shallow coastal waters of Vietnam. The structure of archasteroside C was determined by 2D NMR spectroscopy and electrospray ionization (ESI) tandem mass spectrometry.     

New class of carbohydrate-based nonionic surfactants: diblock co-oligomers of tri-<Emphasis Type="Italic">O</Emphasis>-methylated and unmodified cello-oligosaccharides

Mixtures of diblock co-oligomers of tri-O-methylated and unmodified cello-oligosaccharides have been found to be amphiphilic, as reported before. In order to clarify their accurate amphiphilic property, diblock co-oligomers of tri-O-methylated and unmodified cello-oligosaccharides with monodispersity, methyl β-d-glucopyranosyl-(1→4)-2,3,6–tri-O-methyl-β-d-glucopyranosyl-(1→4)-2,3,6–tri-O-methyl-β-d-glucopyranosyl-(1→4)-2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1→4)-2,3,6-tri-O-methyl-d-glucopyranoside (1, pentamer), methyl β-d-glucopyranosyl-(1→4)- β-d-glucopyranosyl-(1→4)-2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1→4)-2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1→4)-2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1→4)-2,3,6-tri-O-methyl-d-glucopyranoside (2, hexamer), and methyl β-d-glucopyranosyl-(1→4)-2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1→4)- 2,3,6-tri-O-methyl-d-glucopyranoside (3, trimer) were synthesized independently. These compounds had higher surface activities compared to the mixture of diblock co-oligomers of tri-O-methylated and unmodified cello-oligosaccharides and commercially available methylcellulose (MC) SM-4. This paper describes the methods of synthesis of these compounds, and the influence of amphiphilic character on their surface activity. A new class of carbohydrate-based nonionic surfactant without long alkyl chain was discovered.     

New triterpenoid glycosides fromThalictrum minus L.

From the terrestrial part ofThalictrum minus L. (Ranunculaceae) a novel triterpenoid diglycoside was isolated. The genin of this glycoside is a new cycloartane triterpenoid. The structure of the glycoside was established on the basis of 1D and 2D NMR spectroscopy and FAB mass spectrometry as 22S,25-epoxy-3-O-β-d-galactopyranosyl-29-O-β-d-glucopyranosyl-9β, 19-cyclo-20S-lanostane-3β,16β,24S,29-tetrol. For Part 10 see Ref. 1. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 602–605, March, 1999.     

Evasteriosides A and B and other sulfated steroids from the Pacific starfish <Emphasis Type="Italic">Evasterias retifera</Emphasis>

Two new polar steroidal glycosides identified as sodium (20R,22E,24R,25S)-3-O-(β-d-xylopyranosyl)-24-methyl-5α-cholest-22-ene-3β,6β,8,15α,26-pentol 26-sulfate (evasterioside A) and sodium (20R,22E)-24-O-(β-d-xylopyranosyl)-5α-cholest-22-ene-3β,6β,8,15α,24-pentol 3-sulfate (evasterioside B) were isolated from the Pacific starfish Evasterias retifera collected in the Sea of Japan. Five known compounds, viz., coscinasterioside B, aphelasterioside A, marthasterone 3-sulfate and (20R)-cholest-7-en-3β-ol and cholesterol sulfates, were identified. The structures of the new natural compounds were established using their 2D NMR and mass spectra and some chemical transformations.     

Five-membered 2,3-dioxo heterocycles: LXXVI. Reaction of methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates with 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione

Methyl 1-aryl-3-benzoyl-4,5-dioxo-4,5-dihydro-1H-pyrrole-2-carboxylates reacted with 6-amino-1,3-dimethylpyrimidine-2,4(1H,3H)-dione to give methyl 11-aryl-12-benzoyl-9-hydroxy-4,6-dimethyl-3,5,10-trioxo-4,6,8,11-tetraazatricyclo[7.2.1.0^2,7]dodec-2(7)-ene-1-carboxylates which underwent thermal recyclization to 1-aryl-3-benzoyl-4-hydroxy-1′,3′-dimethylspiro[pyrrole-2,5′-pyrrolo[2,3-d]pyrimidine]-2′,4′,5,6′(1H,1′H,3′H,7′H)-tetraones.     

Inhibitory Effects of 2,6-Di-O-methyl-3-O-acetyl-β-cyclodextrins with Various Degrees of Substitution of Acetyl Group on Macrophage Activation and Endotoxin Shock Induced by Lipopolysaccharide

The effects of 2,6-di-O-methyl-3-O-acetyl-β-cyclodextrins (DMA-β-CyD) with various degrees of substitution (DS) of an acetyl group of 1.5, 3.8, 6.3 and 7, which are abbreviated to DMA2-β-CyD, DMA4-β-CyD, DMA6-β-CyD and DMA7-β-CyD, respectively, on murine macrophage activation and endotoxin shock induced by lipopolysaccharide (LPS) were examined. Of four DMA-β-CyDs used in the present study, cytotoxicity of DMA-β-CyDs in RAW264.7 cells, a murine macrophage-like cell line, decreased with an increase in the DS values of DMA-β-CyD, and DMA7-β-CyD had no cytotoxicity on RAW264.7 cells up to 100 mM. DMA2-β-CyD and DMA7-β-CyD at the concentration of 5 mM had greater inhibitory effects on nitric oxide (NO) production in RAW264.7 cells stimulated with LPS than DMA4-β-CyD and DMA6-β-CyD. In addition, these inhibitory effects of DMA2-β-CyD and DMA7-β-CyD were concentration-dependent. In the in vivo study, all of the mice died within 12 h after intraperitoneal administration of the solution containing LPS and d-galactosamine. When 100 mM DMA7-β-CyD was concomitantly administered with both LPS and d-galactosamine intraperitoneally in mice, the survival rate significantly increased, but DMA4-β-CyD and DMA6-β-CyD did not. In conclusion, we revealed that DS values of DMA-β-CyDs strikingly affect not only the cytotoxic activity but also the inhibitory effects of LPS-induced NO production in RAW264.7 cells and fatality of endotoxin shock mice induced by LPS and d-galactosamine. These results suggest the potential use of DMA7-β-CyD as an antagonist of LPS-induced endotoxin shock.     

ABA- and BAB-triblock cooligomers of tri-<Emphasis Type="Italic">O</Emphasis>-methylated and unmodified cello-oligosaccharides: syntheses and structure-solubility relationship

Triblock cooligomers consisting of tri-O-methyl-glucopyranosyl and unmodified glucopyranosyl residues, methyl 2,3,4,6-tetra-O-methyl-β-d-glucopyranosyl-(1 → 4)-2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1 → 4)-β-d-glucopyranosyl-(1 → 4)-β-d-glucopyranosyl-(1 → 4)-2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1 → 4)-2,3,6-tri-O-methyl-α-d-glucopyranoside (1: ABA triblock cooligomer; DS = 2.1) and β-d-glucopyranosyl-(1 → 4)-2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1 → 4)-2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1 → 4)-2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1 → 4)-2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1 → 4)-d-glucopyranose (2: BAB triblock cooligomer; DS = 1.8) were prepared. Compound 1 dissolved both in distilled water and chloroform but compound 2 dissolved in distilled water not in chloroform, though compounds 1 and 2 consist of 4 tri-O-methyl-glucopyranosyl and 2 unmodified anhydro glucopyranosyl units.     

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.     

New thiazinediones and other components from Xanthium strumarium

Two new thiazinediones along with five known compounds were isolated from the fruits of Xanthium strumarium L. The structures of the two new compounds were determined to be 7-hydroxymethyl-8,8-dimethyl-4,8-dihydrobenzol[1,4]thiazine-3,5-dione-11-O-β-D-glucopyranoside (1) and 2-hydroxy-7-hydroxymethyl-8,8-dimethyl-4,8-dihydrobenzol[1,4]thiazine-3,5-dione-11-O-β-D-glucopyranoside (2). The five known compounds were identified as xanthiazone (3), chlorogenic acid (4), ferulic acid (5), formononetin (6), and ononin (7), respectively. Published in Khimiya Prirodnykh Soedinenii, No. 5, pp. 456–458, September–October, 2006.     

Synthesis of saccharide precursors for preparation of potential inhibitors of glycosyltranferases

Ethyl 6-O-tert-butyldimethylsilyl-3,4-di-O-acetyl-2-thio-α-D-fructofuranoside (Va), its β-analog (Vb); as well as benzyl 6-O-tert-butyldimethylsilyl-3,4-di-O-acetyl-2-thio-α-D-fructofuranoside (Xa) and its β-analog (Xb), having an unprotected OH group at C-1, were prepared by sequential synthesis starting from commercially available D-fructose. These compounds represent suitable nucleophiles for the preparation of model carbohydrate mimetics of a glycosyltransferase inhibitor type in transition state. The structures of all compounds were confirmed by NMR spectral data and elemental analyses.     

Selection of protecting groups and synthesis of a β-1,4-GlcNAc-β-1,4-GlcN unit

Abstract  

The synthesis of the disaccharide tert-butyldimethylsilyl (4-O-acetyl-2-azido-3,6-di-O-benzyl-2-deoxy-β-d-glucopyranosyl)-3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranoside, designed as a repeating unit appearing in oligo- and polysaccharides, which exhibits a distinguished “obverse–reverse” property in β-1,4-glucan chain, was accomplished. This disaccharide was synthesized by glycosylation of a phthalimido sugar with an azido sugar. A selective removal of the two different protecting groups at C-2 for obtaining 2-acetamido-4-O-(2-amino-2-deoxy-β-d-glucopyranosyl)-2-deoxy-β-d-glucopyranose indicates that the selection and combination, using phthalimido and azido as protecting groups, are an excellent strategy for synthesizing such target disaccharides.     

The structure and13C NMR spectra of mannitol oligo-β-d-glucopyranosides isolated from the brown seaweedChorda filum (L.) Lam

1-O-β-d-Glucopyranosyl-d-mannitol, 1,6-di-O-glucopyranosyl-d-mannitol, 1-O-β-gentiobiosyl-d-mannitol, 1-O-β-gentiobiosyl-6-O-β-d-glucopyranosyl-d-mannitol, and 1-O-β-d-gentiotriosyl-d-mannitol were isolated from the brown seaweedChorda filum and the assignment of signals in their¹³C NMR spectra was performed. Comparative analysis of the oligosaccharide composition and the structure of laminarans from seven brown algae demonstrates that the oligosaccharides are not always fragments of the corresponding laminarans. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1817–1820, October, 1993.     

Block co-oligomers of tri-O-methylated and unmodified cello-oligosaccharides as model compounds for methylcellulose and its dissolution/gelation behavior

A novel synthetic method for co-oligomers of tri-O-methylated and unmodified cello-oligosaccharides was designed. These oligomers are of importance as model compounds for investigations on the dissolution behavior of commercial methylcelluloses. In this connection, insights into the chemical structure of ‘cross linking loci’ in the thermo reversible gelation of aqueous solution of methylcellulose are of particular significance. The synthetic procedure consists of glycosylation using glycosyl fluoride and oligomerization of sugar orthoester. Thus, phenyl 2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1→4)-2,3,6-tri-O-methyl-1-thio-β-d-glucopyranoside (1) as a glycosyl acceptor was glycosylated with 4-O-acetyl-2,3,6-tri-O-methyl-β-d-glucopyranosyl-(1→4)-2,3,6-tri-O-methyl-d-glucopyranosyl fluoride (2) as a glycosyl donor converted to give a cellotetraose derivative (3). Both reactants have been prepared from commercially available cellobiose. After deacetylation of 3, 3-O-benzyl-6-O-pivaloyl-α-d-glucopyranose 1,2,4-orthopivalate (5) was reacted with 4-hydroxyl group at non-reducing-end of cellotetraose derivative (4) to give the block co-oligomer (6). After the deprotection of compound 6, tri-O-methylated-block-unmodified cello-oligosaccharides (18 and 18′) (DP = 4 − 8, DS = 2.79 − 1.38) were obtained, monitored by MALDI-TOF MS spectra. Chloroform-soluble methylated cellotetraose derivatives (18 and 18′ (DP=4, n=0), DS=2.57, and 2.79, respectively) were also soluble in the water solution of tri-O-methylated-block-unmodified cello-oligosaccharides (DP=4−8, DS=2.79−1.50). This fact indicated that hydrophobic methylated cello-tetraose derivatives were encapsulated within a micelle of amphiphlic tri-O-methylated-block-unmodified cello-oligosaccharides. It was found that solubilities of 18 and 18′ (DP=4−8, DS=2.79−1.38) in water and chloroform were obviously different in the mixtures, depending on their DP and DS values. The substituent distribution of the tri-O-methylated-block-unmodified cello-oligosaccharides along one molecule and between molecules plays an important role in its solubility in water and chloroform.