An aromatic amide C-glycoside and a cyclitol derivative from stem barks of Piper guineense Schum and Thonn (Piperaceae)

Two new compounds, an aromatic amide C-glycoside, 4-C-β-D-glucopyranosyl-3,5-dihydroxy-2-methoxybenzamide (1) and a cyclitol derivative, 4-O-caffeoyl-2-C-methoxycarbonyl-1-C-methyl-2,3,6-trihydroxycyclohexanecarboxylic acid (2), were isolated from the methanol soluble extract of the stem barks of Piper guineense Schum and Thonn, together with four known quinic acids derivatives including 3-O-caffeoyl-1-methylquinic acid (3), 3-O-feruloylquinic acid (4), ethyl-4-O-feruloylquinate (5), and 5-caffeoylquinic acid (6). Their structures were established on the basis of detailed spectroscopic analysis. The radical scavenging activity of the isolates were evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assay. Five of them were found to have significant radical scavenging activities, while compounds 2 and 3 displayed the highest activities with IC₅₀ values of 8.35 and 7.06 μM, respectively.     

Two new quinic acid derivatives and one new lignan glycoside from Erycibe obtusifolia

Three new compounds, 4-{erythro-2-[3-(4-hydroxyl-3-methoxyphenyl)-3-O-β-d-glucopyranosyl-propan-1-ol]}-O-medioresinol (1), (7⿳E,9⿳E,1⿳R*,3⿳S*,5⿳R*,6⿳S*)-5-O-caffeoyl-3-O-dihydrophaseicoylquinic acid (2), and (7⿳E,9⿳E,1⿳R*,3⿳S*,5⿳R*,6⿳S*)-5-O-caffeoyl-4-O-dihydrophaseicoylquinic acid (3), were isolated from Chinese folk herb Erycibe obtusifolia together with six known compounds (4⿿9). Their structures were elucidated on the basis of comparisons of literatures and extensive spectroscopic analysis, including UV, IR, HRMS, and 1D and 2D NMR techniques. Further, the cytotoxicities of these compounds were evaluated against five cell lines (HCT-8, Bel-7402, BGC-823, A549, and A2780), but they were inactive against these tumor cell lines (IC₅₀ > 10 μmol/L).     

The stepwise synthesis of a methyl β-xylotetraoside related to branched xylans

3,4-Di-O-acetyl-2-O-benzyl-α-d-xylopyranosyl bromide (1) reacts with methyl 2,3-anhydro-α-d-ribopyranoside (2) to afford, in high yield, methyl 2,3-anhydro-4-O- (3,4-di-O-acetyl-2-O-benzyl-β-d-xylopyranosyl)-β-d-ribopyranoside (3). Deacetylation of 3 gave 4, which reacted with 2,3,4-tri-O-acetyl-α-d-xylopyranosyl bromide to give the branched tetrasaccharide derivative 5, which, in turn, was converted by a series or conventional reactions into methyl 4-O-[3,4-di-O-(β-d-xylopyranosyl)-β-d- xylopyranosyl]-β-d-xylopyranoside. The reaction of 1 with its hydrolysis product gave 3,4-di-O-acetyl-2-O-benzyl-α-d-xylopyranosyl 3,4-di-O-acetyl-2-O-benzyl-β-d-xylopyranoside, which was also isolated after the reaction of 1 with 2.     

Unusual properties of glycuronans [poly(glycosyluronic) compounds]

2-Methyl-[3,6-di-O-acetyl-2-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-α-d-glucopyrano]-[2,1-d]-2-oxazoline (4) was prepared from 2-acetamido-3,6-di-O-acetyl-2-deoxy-4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-α-d- glucopyranosyl chloride. Condensation of 3,4:5,6-di-O-isopropylidene-d-mannose dimethyl acetal with 4 in the presence of a catalytic amount of p-toluenesulfonic acid afforded O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-(1 → 4)-O-(2-acetamido-3,6-di-O-acetyl-2-deoxy-β-d-glucopyranosyl)-(1 → 2)-3,4:5,6-di-O-isopropylidene-d-mannose dimethyl acetal (6) in 8.6% yield. Catalytic deacetylation of 6 with sodium methoxide, followed by hydrolysis with dilute sulfuric acid, gave O-β-d-galactopyranosyl-(1 → 4)-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1 → 2)-d-mannose (7). The inhibitory activities of 7 and related sugars against the hemagglutinating activities of various lectins were assayed, and 7 was found to be a good inhibitor against Phaseolus vulgaris hemagglutinin.     

The linkage of 4-O-methyl-L-galactose in the sulphated polysaccharide of Aeodes ulvoidea

Methyl 2-acetamido-5,6-di-O-benzyl-2-deoxy-β-d-glucofuranoside (11) was obtained in six steps from the known methyl 3-O-allyl-2-benzamido-2-deoxy-5,6-O-isopropylidene-β-d-glucofuranoside. Mild acid hydrolysis, followed by benzylation gave the 5,6-dibenzyl ether. The benzamido group was exchanged for an acetamido group by strong alkaline hydrolysis, followed by N-acetylation, and the allyl group was isomerized into a 1-propenyl group that was hydrolyzed with mercuric chloride. Treatment of 11 with l-α-chloropropionic acid and with diazomethabe gave methyl 2-acetamido-5,6-di-O-benzyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-β-d-glucofuranoside which formed on mercaptolysis the internal ester 16, further converted into 2-acetamido-4-O-acetyl-5,6-di-O-benzyl-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-d-glucose diethyl dithioacetal (18) by alkaline treatment followed by esterification with diazomethane and acetylation. Attempts to remove the O-acetyl group of the corresponding dimethyl acetal 20 with sodium methoxide in mild conditions were not successful.     

A synthesis of psi-cytidine

2-O-Benzoyl-3,6-di-O-benzyl-4-O-(chloroacetyl)-, 4-O-acetyl-2-O-benzoyl-3,6-di-O-benzyl-, and 2-O-benzoyl-3,4,6-tri-O-benzyl-α-d-galactopyranosyl chloride were converted into the corresponding 2,2,2-trifluoroethanesulfonates, and these were treated with allyl 2-O-benzoyl-3,6-di-O-benzyl-α-d-galactopyranoside, to give allyl 2-O-benzoyl-4-O-[2-O-benzoyl-3,6-di-O-benzyl-4-O-(chloroacetyl)-β-d-galactopyranosyl]-3,6-di-O-benzyl- α-d-galactopyranoside (26; 41% yield), allyl 4-O-(4-O-acetyl-2-O-benzoyl-3,6-di-O-benzyl-β-d-galactopyranosyl)-2-O-benzoyl-3,6-di-O-benzyl- α-d-galactopyranoside (27; 62% yield), and allyl 2-O-benzoyl-4-O-(2-O-benzoyl-3,4,6-tri-O-benzyl-β-d-galactopyranosyl)-3,6-di-O-benzyl-α-d-galactopyranoside (28; 65% yield). All disaccharides were free from their α anomers. Disaccharides 26 and 27 were found to be base-sensitive, and were de-esterified by KCN in aqueous ethanol, and debenzylated with H₂-Pd. Attempts to produce (1→4)-β-d-galactopyranosides from the coupling of a number of fully esterified d-galactopyranosyl sulfonates to allyl 2,3,6-tri-O-benzoyl-α-d-galactopyranoside were unsuccessful.     

Synthesis of 3- and 2′-fucosyl-lactose and 3,2′-difucosyl-lactose from partially benzylated lactose derivatives

O-β-d-Galactopyranosyl-(1→4)-O-[α-l-fucopyranosyl-(1→3)]-d-glucose has been synthesised by reaction of benzyl 2,6-di-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-β-d-galactopyranosyl)-β-d-glucopyranoside with 2,3,4-tri-O-benzyl-α-l-fucopyranosyl bromide in the presence of mercuric bromide, followed by hydrogenolysis. Benzylation of benzyl 3′,4′-O-isopropylidene-β-lactoside, via tributylstannylation, in the presence of tetrabutylammonium bromide or N-methylimidazole, gave benzyl 2,6-di-O-benzyl-4-O-(6-O-benzyl-3,4-O-isopropylidene-β-d-galactopyranosyl)-β-d-glucopyranoside (6). α-Fucosylation of 6 in the presence of tetraethylammonium bromide provided either benzyl 2,6-di-O-benzyl-4-O-[6-O-benzyl-3,4-O-isopropylidene-2-O-(2,3,4-tri-O-benzyl-α-l-fucopyransoyl)-β-d- galactopyranosyl]-β-d-glucopyranoside (13, 73%) or a mixture of 13 (42%) and benzyl 2,6-di-O-benzyl-4-O-[6-O-benzyl-3,4,-O-isopropylidene-2-O-(2,3,4-tri-O-benzyl-α-l-fucopyranosyl)-β-d- galactopyranosyl-3-O-(2,3,4-tri-O-benzyl-α-l-fucopyranosyl)-β-d-glucopyranoside (16, 34%). α-Fucosylation of 13 in the presence of mercuric bromide and 2,6-di-tert-butyl-4-methylpyridine gave 16 (73%). Hydrogenolysis and acid hydrolysis of 13 and 16 afforded O-α-l-fucopyranosyl-(1→2)-O-β-d-galactopyranosyl-(1→4)-d-glucose and O-α-l-fucopyranosyl-(1→2)-O-β-d-galactopyranosyl-(1→4)-O-[α-l-fucopyranosyl-(1→3)]-d-glucose, respectively.     

The action of alkali on di-O-(2-bromoethylidene)-d-mannitols: Formation of an unusually acid-stable acetal linkage

When cis,trans-1,2:5,6-di-O-(2-bromoethylidene)-d-mannitol and cis,cis-1,2:5,6-di-O-(2-bromoethylidene)-d-mannitol were treated with dilute, boiling sodium hydroxide, 5,6-O-(S)-(2-bromoethylidene)-3:1,2-O-[(R)-1-ethanyl-2-ylidene]-d-mannitol (3) and 3:1,2;4:5,6-di-O-[(R)-1-ethanyl-2-ylidene]-d-mannitol (10) were produced; the structures were established by a combination of chemical transformations, ¹H-n.m.r. spectroscopy, and mass spectrometry. The bicyclo ether-acetal linkage in 3 and 10 proved unusually resistant to hydrolysis by acid.     

Dr. Horace S. Isbell

Addition of ethyl isocyanoacetate in strongly basic medium to the glycosuloses 1,2:5,6-di-O-isopropylidene-α-d-ribo-hexofuranos-3-ulose (1) and 1,2-O-isopropylidene-5-O-trityl-d-erythro-pentos-3-ulose (2) gave the unsaturated derivatives (E)- and (Z)-3-deoxy-3-C-ethoxycarbonyl(formylamino)methylene-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (3 and 4), and (E)-3-deoxy-3-C-ethoxycarbonyl(formylamino)methylene-1,2-O-isopropylidene-5-O-trityl-α-d-ribofuranose (5). In weakly basic medium, ethyl isocyanoacetate and 1 gave 3-C-ethoxycarbonyl(formylamino)methyl-1,2:5,6-di-O-isopropylidene-α-d-allofuranose (12) in good yield. The oxidation of 3 and 4 with osmium tetraoxide to 3-C-ethoxalyl-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (17), and its subsequent reduction to 3-C-(R)-1′,2′-dihydroxyethyl-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (18) and its (S) epimer (19) and to 3-C-(R)-ethoxycarbonyl(hydroxy)methyl-1,2:5,6-di-O-isopropylidene-α-d-glucofuranose (21) and its (S) epimer (22) are described. Hydride reductions of 12 yielded the corresponding 3-C-(1-formylamino-2-hydroxyethyl), 3-C-(2-hydroxy-1-methylaminoethyl), and 3-C-(R)-ethoxycarbonyl(methylamino)methyl derivatives (13, 14 and 16). Catalytic reduction of 3 and 4 yielded the 3-deoxy-3-C-(R)-ethoxycarbonyl-(formylamino)methyl derivative 6 and its 3-C-(S) epimer. Further reduction of 6 gave 3-deoxy-3-C-(R)-(1-formylamino-2-hydroxyethyl)-1,2:5,6-di-O-isopropylidene-α-d-allofuranose (23) which was deformylated with hydrazine acetate to 3-C-(R)-(1-amino-2-hydroxyethyl)-3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-allofuranose (24). The configurations of the branched-chains in 16, 21, and 22 were determined by o.r.d.     

The stepwise synthesis of an aldopentaouronic acid derivative related to branched (4-O-methylglucurono)xylans

Benzylation of methyl 2,3-anhydro-4-O-[2-O-benzyl-3,4-di-O-(β-D-xylop yranosyl]-β-D-xylopyranosyl]-β-D-ribopyranoside (1) afforded the crystalline. fully benzylated tetrasaccharide derivative 2. The octa-O-benzyl derivative 3, having only HO-2 unsubstituted, obtained by treatment of 2 with benzyl alcoholate anion in benzyl alcohol, was allowed to react in dichloromethane with methyl 2,3-di-O-benzyl- 1-chloro-1-deoxy-4-O-methy]-α,β-glucopyranuronate in the presence of silver perchlorate and triethylamine to give the branched, 4-O-methyl-α-D-glucuronic acid-containing pentasaccharide derivative 4a as the major product. Subsequent debenzylation afforded the aldopentaouronic acid derivative 5a, which contains all the basic structural features of branched, hardwood (4-O-methylglucurono)xylans. The structure of 5a was confirmed by analysis of its ¹³C-n.m.r. spectrum and the mass-spectral fragmentation pattern of the corresponding fully methylated derivative 6a.     

Synthesis of 2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-D-mannose,and its interaction with D-mannose-specific lectins

Condensation of 3,4:5,6-di-O-isopropylidene-D-mannose dimethyl acetal with 2-methyl-(3,4,6-tri-O-acetyl- 1,2-dideoxy-α-D-glucopyrano)-[2′, 1′:4,5]-2-oxazoline in the presence of a catalytic amount of p-toluenesulfonic acid afforded crystalline 2-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosyl)-3,4:5,6-di-O-isopropylidene-D-mannose dimethyl acetal (3) in 25% yield. Catalytic deacetylation of 3 with sodium methoxide, followed by hydrolysis with dilute sulfuric acid, gave 2-O-(2-acetamido-2-deoxy-α-D-glucopyranosyl)-D-mannose (4). Treatment of 3 with boiling 0.5% methanolic hydrogen chloride under reflux gave methyl 2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-α-D-mannopyranoside (5) and methyl 2-O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-α-D-mannofuranoside (6). The inhibitory activities of 4, 5, and 6 against the hemagglutinating and mitogenic activities of Lens culinaris and Pisum sativum lectins and concanavalin A were assayed. From the results of these hapten inhibition studies, subtle differences of specificity between these D-mannose-specific lectins were confirmed.     

Synthetic mucin fragments. Methyl 6-O-(2-acetamido-2-deoxy-β-D-glycopyranosyl)-β-D-galactopyranoside,methyl 3,4-di-O-(2-acetamido-2-deoxy-β-D-glycopyranosyl)-β-D-galactopyranoside,and methyl O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-(1 å 3)-O-β-D-galactopyranosyl-(1 å 3)-O-(2-acetamido-2-deoxy-β- D-glucopyranosyl)-(1 å 3)-β-D-galactopyranoside

Condensation of methyl 2,6-di-O-benzyl-β-d-galactopyranoside with 2-methyl-(3,4,6-tri-O-acetyl-1,2-dideoxy-α-d-glucopyrano)-[2,1,-d]-2-oxazoline (1) in 1,2-dichloroethane, in the presence of p-toluenesulfonic acid, afforded a trisaccharide derivative which, on deacetylation, gave methyl 3,4-di-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-2,6-di-O-benzyl-β-d- glactopyranoside (5). Hydrogenolysis of the benzyl groups of 5 furnished the title trisaccharide (6). A similar condensation of methyl 2,3-di-O-benzyl-β-d-galactopyranoside with 1 produced a partially-protected disacchraide derivative, which, on O-deacetylation followed by hydrogenolysis, gave methyl 6-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-β-d-glactopyranoside (10). Condensation of methyl 3-O-(2-acetamido-4,6-O-benzylidene-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-benzyl-β-d- galactopyranoside with 3-O-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-d-glucopyranosyl)-2,4,6-tri-O-acetyl-α-d-galactopyranosyl bromide in 1:1 benzene-nitromethane in the presence of powdered mercuric cyanide gave a fully-protected tetrasaccharide derivative, which was O-deacetylated and then subjected to catalytic hydrogenation to furnish methyl O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→3)-O-β-d-galactopyranosyl-(1å3)-O-(2-acetamido-2-deoxy- β-d-glucopyranosyl)-(1å3)-β-d-galactopyranoside (15). The structures of 6, 10, and 15 were established by ¹³C-n.m.r. spectroscopy.     

Synthesis of some C-glycosyl- and polyhydroxyalkyl-pyridazines

Photo-oxygenation of 3-hydroxymethyl-5-(2,3-O-isopropylidene-β-d-erythrofuranosyl)-2-methylfuran, 5-(1,2:3,4-di-O-isopropylidene-d-arabino-tetritol-1-yl)-3-(1-hydroxyethyl)-2-methylfuran (8a), and 2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-arabino-tetritol-1-yl)-3-furoic acid (8b) yielded the corresponding endo-peroxides, which were transformed into 4-hydroxymethyl-6-(2,3-O-isopropylidene-β-d-erythrofuranosyl)-3-methylpyridazine, 6-(1,2:3,4-di-O-isopropylidene-d-arabino-tetritol-1-yl)-4-(1-hydroxyethyl)-3-methylpyridazine, and 6-(d-arabino-tetritol-1-yl)-3-methylpyridazine by treatment with hydrazine. The γ-di-ketones (Z)-1-(1,2:3,4-di-O-isopropylidene-d-arabino-tetritol-1-yl)-3-(1-hydroxyethyl)pent-2-ene-1,4-dione and d-arabino-6,7,8,9-tetraacetoxy-4-methoxynonane-2,5-dione can be obtained by reduction of the endo-peroxides 9a and 9b (derived from 8a and 8b, respectively) with dimethyl sulphide. The C → O rearrangement reported for C-glycosyl endo-peroxides was also observed for 9a.     

Isolation of phenolic constituents and characterization of antioxidant markers from sunflower (Helianthus annuus) seed extract

A new compound, benzyl alcohol β-d-apiofuranosyl-(1→6)-β-d-(4-O-caffeoyl) glucopyranoside (1), was isolated from the seed of sunflower (Helianthus annuus), together with eight known phenolic compounds: caffeic acid (2), methyl caffeoate (3), chlorogenic acid (4), 4-O-caffeoylquinic acid (5), 3-O-caffeoylquinic acid (6), methyl chlorogenate (7), 3,5-di-O-caffeoylquinic acid (8), and eriodictyol 5-O-β-d-glucoside (9). Their structures were elucidated on the basis of spectroscopic methods and chemical evidence. The antioxidative effect of the phenolic constituents from the sunflower seeds was also evaluated based on the oxygen-radical absorbance capacity (ORAC), and the fraction containing caffeic acid derivatives showed a high antioxidant potency.     

C-4′-Branched-chain sugar nucleosides: synthesis of isomers of psicofuranine

Photoamidation of 3-O-acetyl-1,2:5,6-di-O-isopropylidene-α-d-erythro-hex-3-enofuranose (1) afforded 3-O-acetyl-4-C-carbamoyl-1,2:5,6-di-O-isopropylidene-α-d-gulofuranose (2) and 3-O-acetyl-3-C-carbamoyl-1,2:5,6-di-O-isopropylidene-d-α-allofuranose (3) in 65 and 26% yields, respectively (based on consumed1). Treatment of2 with 5% hydrochloric acid in methanol yielded the spiro lactone5, which was deacetylated to yield7. Reduction of5 with sodium borohydride afforded 4-C-(hydroxymethyl)-1,2-O-isopropylidene-α-d-gulofuranose (9) in 79% yield. Oxidation of9 with sodium metaperiodate afforded a dialdose that was reduced with sodium borohydride to give 4-C-(hydroxymethyl)-1,2-O-isopropylidene-α-d-erythro-pentofuranose (11) in 88% yield. Treatment of the acetate12, derived from11, with trifluoroacetic acid, followed by acetylation, afforded the branched-chain sugar acetate14. Condensation of the glycosyl halide derived from14 withN⁶-benzoyl-N⁶, 9-bis-(trimethylsilyl)adenine yielded an equimolar anomeric mixture of protected nucleosides15 and16 in 40% yield. Treatment of the latter compounds with sodium methoxide in methanol afforded 9-[4-C-(hydroxymethyl)-β-d-erythro-pentofuranosyl]-adenine (17) and the α-d anomer18. The structure of3 was determined by correlation with the known 5,3′-hemiacetal of 3-C-(hydroxymethyl)-1,2-O-isopropylidene-α,α′-d-ribo-pentodialdose (25).     

Synthesis of a tetrasaccharide donor corresponding to the O-specific polysaccharide of Shigella dysenteriae type 1

O-(2,4-Di-O-chloroacetyl-α-l-rhamnopyranosyl)-(1 → 2)-O-(3,4,6-tri-O-benzoyl-α-d-galactopyranosyl)-(1 → 3)-O-(2-acetamido-4,6-di-O-acetyl-2-deoxy-α-d-glycopyranosyl)-(1 → 3)-2,4-di-O-benzoyl-α-l-rhamnopyranosyl trichloroacetimidate (1) was synthesized in a stepwise manner, using the following monosaccharide units: 2-(trimethylsilyl)ethyl 2,4-di-O-benzoyl-α-l-rhamnopyranoside, 2-azido-4,6-O-benzylidene-3-O-chloroacetyl-2-deoxy-β-d-glycopyranosyl chloride, methyl 3,4,6-tri-O-benzoyl-2-O-(4-methoxybenzyl)-1-thio-β-d-galactopyranoside, and 2,4-di-O-benzoyl-3-O-chloroacetyl-α-l-rhamnopyranosyl chloride. Compound 1 corresponds to a complete tetrasaccharide repeating unit of the O-specific polysaccharide of the lipopolysaccharide of Shigella dysenteriae type 1.     

Thiophenes,polyacetylenes and terpenes from the aerial parts of Eclipata prostrata

One new bithiophenes, 5-(but-3-yne-1,2-diol)-5′-hydroxy-methyl-2,2′-bithiophene (2), two new polyacetylenic glucosides, 3-O-β-d-glucopyranosyloxy-1-hydroxy-4E,6E-tetradecene-8,10,12-triyne (8), (5E)-trideca-1,5-dien-7,9,11-triyne-3,4-diol-4-O-β-d-glucopyranoside (9), six new terpenoid glycosides, rel-(1S,2S,3S,4R,6R)-1,6-epoxy-menthane-2,3-diol-3-O-β-d-glucopyranoside (10), rel-(1S,2S,3S,4R,6R)-3-O-(6-O-caffeoyl-β-d-glucopyranosyl)-1,6-epoxy menthane-2,3-diol (11), (2E,6E)-2,6,10-trimethyl-2,6,11-dodecatriene-1,10-diol-1-O-β-d-glucopyranoside (12), 3β,16β,29-trihydroxy oleanane-12-ene-3-O-β-d-glucopyranoside (13), 3,28-di-O-β-d-glucopyranosyl-3β,16β-dihydroxy oleanane-12-ene-28-oleanlic acid (14), 3-O-β-d-glucopyranosyl-(1→2)-β-d-glucopyranosyl oleanlic-18-ene acid-28-O-β-d-glucopyranoside (15), along with fifteen known compounds (1, 3–7, and 16–24), were isolated from the aerial parts of Eclipta prostrata. Their structures were established by analysis of the spectroscopic data. The isolated compounds 1–9 were tested for activities against dipeptidyl peptidase IV (DPP-IV), compound 7 showed significant antihyperglycemic activities by inhibitory effects on DPP-IV in human plasma in vitro, with IC₅₀ value of 0.51 μM. Compounds 10–24 were tested in vitro against NF-κB-luc 293 cell line induced by LPS. Compounds 12, 15, 16, 19, 21, and 23 exhibited moderate anti-inflammatory activities.     

Studies of carbohydrate derivatives having the -CH2F function

The following primary sulphonates have been converted into the corresponding deoxyfluoro derivatives by reaction with potassium fluoride in ethylene glycol:1,2:3,4-di-O-isopropylidene-6-O-tosyl α-D-galactopyranose (1), methyl 2,3-O2-isopropyliden-5-O-tosyl-α,β-D-ribofuranoside (2), 1,2:3,4-di-O-methylene-6-O-tosyl-α-D-glucofuranose (3), 3,5-di-O-benzylidene-1,2-O-isopropylidene-6-O-tosyl-α-D-glucofuranose (4), and 1,2:3,5-di-O-isopropylidene-6-O-tosyl-α-D-glucofuranose (5). The yields were generally poor; in the reaction of 1, a major by-product was 6-O-(2-hydroxyethyl)-1,2:3,4-di-O-isopropylidene-α-D-galactopyranose (11). The reaction of the primary hydroxyl precursor of each of the above tosylates with N2-(2-chloro- 1,1,2-trifluoroethyl)-N,N-diethylamine generally yielded the O-chlorofluoroacetyl derivative; however, 1,2:3,5-di-O-methylene-α-D-glucofuranose (12) was converted into the 6-deoxy-6-fluoro derivative (8). The ¹⁹F resonances of compounds containing the CH₂F moiety fall between φ_C +213 and φ_C +235 p.p.m. The differences between the vicinal¹⁹F-¹H couplings of compounds having the D-gluco and D-galacto configurations clearly reflect the influence of the C-4O-4 substitutents on the populations of the C-5C-6 rotamers. A novel type of noise-modulated, heteronuclear decoupling experiment is described.     

Synthesis of 1-deoxy-3-C-methyl-d-fructose and 1-deoxy-3-C-methyl-d-sorbose

Hydroxylation of trans-1,3,4-trideoxy-5,6-O-isopropylidene-3-C-methyl-d-glycero-hex-3-enulose with osmium tetraoxide gave a mixture of 1-deoxy-5,6-O-isopropylidene-3-C-methyl-d-arabino- and -d-xylo-hexulose that was partially resolved by acetonation to give 1-deoxy-2,3:4,5-di-O-isopropylidene-3-C-methyl-β-d-fructopyranose (4), 1-deoxy-3,4:5,6-di-O-isopropylidene-3-C-methyl-keto-d-fructose (5), and 1-deoxy-2,3:4,6-di-O-isopropylidene-3-C-methyl-α-d-sorbofuranose (6). Treatment of a mixture of 4 and 5 with sodium borohydride gave, after column chromatography, 4 and 1-deoxy-3,4:5,6-di-O-isopropylidene-3-C-methyl-d-manno- and -d-gluco-hexitol. Deuterated derivatives corresponding to 4–6 were obtained when isopropylidenation was carried out with acetone-d₆. Deacetonation of 4 and 5 yielded 1-deoxy-3-C-methyl-d-fructose, and 6 similarly afforded 1-deoxy-3-C-methyl-d-sorbose.     

Synthesis of 2- (and 6-) -dithian-2-yluracil nucleosides and their conversion into nucleoside derivatives

Addition of 2,2′-anhydro-[1-(3-O-acetyl-5-O-trityl-β-D-arabinofuranosyl)uracil] (1) to excess 2-litho-1,3-dithiane (2)in oxolane at ?78° gave 2-(1,3-dithian-2-yl)-1-(5-O-trityl-β-D-arabinofuranosyl)-4(1H)pyrimidinone (3), O²,2′-anhydro-5,6-di-hydro-6-(S)-(1,3-dithian-2-yl)-5′-O-trityluridine (4), and 2-(1,4-dihydroxybutyl)-1,3-dithiane (5) in yields of 15, 30, and 10% respectively. The structure of 3 was proved by its hydrolysis in acid to give 2-(1,3-dithian-2-yl)-4-pyrimidinone (6) and arabinose, and by desulfurization with Raney nickel to yield the known 2-methyl-1-(5-O-trityl-β-D-arabinofuranosyl)-4(1H)-pyrimidinone (7). Detritylation of 3 without glycosidic cleavage could only be effected by prior acetylation to 1-(2,3-di-O-acetyl-5-O-trityl-β-D-arabinofuranosyl)-2-(1,3-dithian-2-yl)-4(1H)-pyrimidinone (8) which, after treatment with acetic acid at room temperature for 65 h followed by the action of sodium methoxide gave 2-(1,3-dithian-2-yl)-1-β-D-arabinofuranosyl-4(1H)-pyrimidinone (10) in 45% yield. Detritylation of 4 in boiling acetic acid gave 5,6-dihydro-6-(S)-(1,3-dithian-2-yl)-1-β-D-arabinofuranosyluracil (12) and 3-[(S)-1-(1,3-dithian-2-yl)]propionamido-(1,2-dideoxy-β-D-arabinofurano)-[1,2-d]-2-oxazolidinone (13) in 10 and 90% yields, respectively. When 12 was kept in water or methanol for 7 days, quantitative conversion into 13 occurred. Acid hydrolysis of 12 afforded arabinose and 5,6-di-hydro-6-(1,3-dithian-2-yl)uracil (14), which was desulfurized with Raney nickel to the known 5,6-dihydro-6-methyluracil (15). Treatment of 13 with trifluoroacetic anhydride-pyridine yielded 77% of the cyano derivative 17. Similar dehydration of 3-(R)-1-methylpropionamido-(1,2-dideoxy-β-D-arabinofurano)-[1,2-d]-2-oxalidinone (18), obtained by desulfurization of 13, gave 60% of the nitrile 19. Hydrogenation of 19 over platinum oxide in acetic anhydride gave the acetamide derivative 20 in 95% yield. Nitrobenzoylation of 13 gave 3-[(S)-1-(1,3-dithian-2-yl)]cyanomethyl-3,5-di-O-p-nitrobenzoyl-(1,2-dideoxy-β-D-arabinofurano)-[1,2-d]-2-oxazolidinone (22), which was converted in 37% yield by treatment with methyl iodide in dimethyl sulfoxide into the aldehyde 24, characterized as the semicarbazone 25. The purification of 5 and its characterization as 2-(1,4-di-O-p-nitrobenzoylbutyl)-1,3-dithiane (27) is described.