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.     

Synthesis of 2,6-di(acylamino)-2,6-dideoxy-3-O-(d-2-propanoyl-l-alanyl-d-isoglutamine)-d-glucopyranoses

Five 2,6-di(acylamino)-2,6-dideoxy-3-O-(d-2-propanoyl-l-alanyl-d-isoglutamine)-d-glucopyranoses (lipophilic, muramoyl dipeptide analogs) were synthesized from benzyl 2-(benzyloxycarbonylamino)-3-O-(d-1-carboxyethyl)-2-deoxy-5,6-O-isopropylidene-β-dglucopyranoside (1). Methanesulfonylation of 3, derived from the methyl ester of 1 by O-deisopropylidenation, gave the 6-methanesulfonate (4). (Tetrahydropyran-2-yl)ation of 4 gave benzyl 2-(benzyloxycarbonylamino)-2-deoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-6-O-(methylsulfonyl)-5-O-(tetrahydropyran-2-yl)-β-d- glucofuranoside, which was treated with sodium azide to give the corresponding 6-azido derivative (6). Condensation of benzyl 6-amino-2-(benzyloxycarbonyl-amino)-2,6-dideoxy-3-O-[d-1-(methoxycarbonyl)ethyl]-5-O-(tetrahydropyran-2-yl)-β-d-glucofuranoside, derived from 6 by reduction, with the activated esters of octanoic, hexadecanoic, and eicosanoic acid gave the corresponding 6-N-fatty acyl derivatives (8–10). Coupling of the 2-amino derivatives, obtained from compounds 8, 9, and 10 by catalytic reduction, with the activated esters of the fatty acids, gave the 2,6-(diacylamino)-2,6-dideoxy derivatives (11–15). Condensation of the acids, formed from 11–15 by de-esterification, with the benzyl ester of l-alanyl-d-isoglutamine, and subsequent hydrolysis, afforded benzyl 2,6-di(acylamino)-2,6-dideoxy-3-O-(d-2-propanoyl-l-alanyl-d-isoglutamine benzyl ester)-β-d-glucofuranosides. Hydrogenation of the dipeptide derivatives thus obtained gave the five lipophilic analogs of 6-amino-6-deoxymuramoyl dipeptide, respectively, in good yields.     

Synthesis,crystal structure,and conformation of 1(S)-acetoxy-3-[6(R)-O-benzyl-1,2:3,4-di-O-isopropylidene-α-d-galactopyranos-6-yl]-1-(methyl 2,3,4-tri-O-benzyl-6-deoxy-β-d-galactopyranosid-6-yl)propyne

Condensation of 6-O-benzyl-7,8-dideoxy-1,2:3,4-di-O-isopropylidene-d-glycero-α-d-galacto-oct-7-ynopyranose with methyl 2,3,4-tri-O-benzyl-6-deoxy-β-d-galacto-heptodialdo-1,5-pyranoside afforded a 2:1 mixture of the 1S and 1R isomers (1a and 1b) of 3-[6(R)-O-benzyl-1,2:3,4-di-O-isopropylidene-α-d-galactopyranos-6-yl]-1-hydroxy-1-(methyl 2,3,4-tri-O-benzyl-6-deoxy-β-d-galactopyranosid-6-yl)propyne. A single crystal of the 1-O-acetyl derivative (1c) of 1a was investigated by X-ray diffraction methods in a four-circle diffractometer. Compound 1c crystallises in the monoclinic system, space group P2₁ (Z = 2) with cell dimensions a = 14.896(2), b = 8.295(1), c = 20.547(3) Å, and β = 102.66(1)°. The structure was solved by direct methods and refined by a full-matrix, least-squares procedure against 3839 unique reflections (F > 2σ_F), resulting in a final R = 0.045 (unit weights). The configuration at the new chiral center (C-1) was established as S(d). The galactopyranose rings have conformations ⁴C₁ (tri-O-benzylated moiety) and °S₅ + °T₂ (di-O-isopropylidenated moiety). The 1,2- and 3,4-O-isopropylidene rings have ³T₂ and ²E conformations, respectively.     

Synthesis of a 2-acetamido-5-amino-2,5-dideoxy-d-xylopyranosyl derivative

2-Acetamido-5-amino-2,5-dideoxy-d-xylopyranosyl hydrogensulfite (11) has been synthesized from benzyl 2-(benzyloxycarbonylamino)-2-deoxy-5,6-O-isopro-pylidene-β-d-glucofuranoside (1). O-Deisopropylidenation of 1 gave the triol 2, which was converted, via oxidative cleavage at C-5-C-6 and subsequent reduction, into the related benzyl β-d-xylofuranoside derivative (3). Catalytic reduction of benzyl 2-(benzyloxycarbonylamino)-2-deoxy-5-O-tosyl-β-d-xylofuranoside, derived from 3 by selective tosylation, and subsequent N-acetylation, afforded benzyl 2-acetamido-2-deoxy-5-O-tosyl-β-d-xylofuranoside, which was treated with sodium azide to give the corresponding 5-azido derivative (6). (Tetrahydropyran-2-yl)ation of the product formed by hydrolysis of 6 gave 2-acetamido-5-azido-2,5-dideoxy-1,3- di-O-(tetrahydropyran-2-yl)-d-xylofuranose (9). Treatment of 2-acetamido-5-amino-2,5-dideoxy-1,3-di-O-(tetrahydropyran-2-yl)-d-xylofuranose, derived from 9 by reduction, with sulfur dioxide in water gave 11. Hydrogenation of 6 and subsequent acetylation yielded 3-acetamido-4,5-diacetoxy-1-acetyl-xylo-piperidine. Evidence in support of the structures assigned to the new derivatives is presented.     

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.     

Glycosides from Breynia fruticosa and Breynia rostrata

Glycosides, 3-acetyl-(?)-epicatechin 7-O-β-glucopyranoside (1), 3-acetyl-(?)-epicatechin 7-O-(6-isobutanoyloxyl)-β-glucopyranoside (2), 3-acetyl-(?)-epicatechin 7-O-[6-(2-methyl-butanoyloxyl)]-β-glucopyranoside (3), (5Z)-6-[5-(2-hydroxypropan-2-yl)-2-methyl-tetrahydrofuran-2-yl]-3-methylhexa-1,5-dien-3-O-β-glucopyranoside (4), hydroquinone O-[6-(3-hydroxyisobutanoyl)]-β-galactopyranoside (5), 4-(4-O-β-glucopyranosyl-phenoxy)-1-O-β-glucopyranosyl-1,3-benzenediol (6), 7,8-erythro-dihydroxy-3,4,5-trimethoxy-phenyl-propane8-O-β-glucopyranoside (7), 6,7-dimethylbenzofuranol 5-O-β-xylopyranosyl-(1 → 6)-β-glucopyranoside (8), along with 30 known glycosides, were isolated from Breynia fruticosa and Breynia rostrata (Euphorbiaceae). Their structures were determined on the basis of spectroscopic analysis and chemical methods.     

Photochemical addition of 1,3-dioxolane and of 2-propanol to 1,2,4,6-tetra-O-acetyl-3-deoxy-α- and -β-D-erythro-hex-2-enopyranose

Photoirradiation of a solution of 1,2,4,6-tetra-O-acetyl-3-deoxy-β-D-erythro-hex-2-enopyranose (1) in 1:50 acetone-1,3-dioxolane with a high-pressure mercury-lamp, followed by chromatographic separation, gave 1,2,4,6-tetra-O-acetyl-3-deoxy-3-C-(1,3-dioxolan-2-yl)-β-D-glucopyranose (3) (44%) and-mannopyranose (4) (35%). Similar treatment of the α anomer (2) of 1 afforded 1,2,4,6-tetra-O-acetyl-3-deoxy-3-C-(1,3-dioxolan-2-yl)-α-D-glucopyranose (5) (38%), -mannopyranose (6) (31%), and -allopyranose (7) (21%).On the other hand, irradiation of 2 in 1:100 acetone-2-propanol gave 1,2,4,6-tetra-O-acetyl-3-deoxy-3-C-(1-hydroxy-1-methylethyl)-α-D-mannopyranose (8) (76%). Moreover, irradiation of 2 in 1:1 acetone-2-propanol yielded 1,4,6-tri-O-acetyl-3-deoxy-2,3-di-C-(1-hydroxy-1-methylethyl)-α-D-gluco- or -manno-pyranose 2,2¹,3¹-orthoacetate (10) (15%), in addition to 8 (44%).     

Synthesis of carbon-11-labeled CK1 inhibitors as new potential PET radiotracers for imaging of Alzheimer’s disease

The reference standards methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate (5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-methoxybenzamide (5c), and their corresponding desmethylated precursors 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoic acid (6a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-hydroxybenzamide (6b), were synthesized from 5-amino-2,2-difluoro-1,3-benzodioxole and 3-substituted benzoic acids in 5 and 6 steps with 33% and 11%, 30% and 7% overall chemical yield, respectively. Carbon-11-labeled casein kinase 1 (CK1) inhibitors, [¹¹C]methyl 3-((2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)carbamoyl)benzoate ([¹¹C]5a) and N-(2,2-difluoro-5H-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]imidazol-6-yl)-3-[¹¹C]methoxybenzamide ([¹¹C]5c), were prepared from their O-desmethylated precursor 6a or 6b with [¹¹C]CH₃OTf through O-[¹¹C]methylation and isolated by HPLC combined with SPE in 40–45% radiochemical yield, based on [¹¹C]CO₂ and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the molar activity (MA) at EOB was 370–740?GBq/μmol with a total synthesis time of ～40-min from EOB.     

Synthesis of 6-substituted uridines. synthesis of (R or S)-6-(3-amino-2-carboxypropyl)uridine

Addition of 5-bromo-2′,3′-O-isopropylidene-5′-O-trityluridine (2) in pyridine to an excess of 2-lithio-1,3-dithiane (3) in oxolane at 78° gave (6R)-5,6-dihydro-(1,3-dithian-2-yl)-2′,3′-O-isopropylidene -5′-O-trityluridine (4), (5S,6S)-5-bromo-5,6-dihydro-(1,3-dithian-2-yl)-2′,3′-O-isopropylidene-5′-O-trityluridine (5), and its (5R) isomer 6 in yields of 37, 35, and 10%, respectively. The structure of 4 was proved by Raney nickel desulphurization to (6S)-5,6-dihydro-2′,3′-O-isopropylidene-6-methyl-5′-O-trityluridine (7) and by acid hydrolysis to give D-ribose and (6R)-5,6-dihydro-6-(1,3-dithian-2-yl)uracil (9). Treatment of 4 with methyl iodide in aqueous acetone gave a 30&%; yield of (R,S)-5,6-dihydro-6-formyl-2′,3′-O-isopropylidene-5′-O-trityl-uridine (10), characterized as its semicarbazone 11. Both 5 and 6 gave 4 upon brief treatment with Raney nickel. Both 5 and 6 also gave 6-formyl-2′,3′-O-isopropylidene-5′- O-trityluridine (12) in ～41%; yield when treated with methyl iodide in aqueous acetone containin- 10%; dimethyl sulfoxide. A by-product, identified as the N-methyl derivative (13) of 12 was also formed in yields which varied with the amount of dimethyl sulfoxide used. Reduction of 12 with sodium borohydride, followed by deprotection, afforded 6-(hydroxymethyl)uridine (17), characterized by hydrolysis to the known 6-(hydroxymethyl)uracil (18). Knoevenagel condensation of a mixture of the aldehydes 12 and 13 with ethyl cyanoacetate yielded 38%; of E- (or Z-)6-[(2-cyano-2-ethoxycarbonyl)ethylidene]-2′,3′-O-isopropylidene-5′-O-trityluridine (19) and 10%; of its N-methyl derivative 20. Hydrogenation of 19 over platinum oxide in acetic anhydride followed by deprotection gave R (or S)-6-(3-amino-2-carboxypropyl)uridine (23).     

Synthesis of methyl O-(3-deoxy-3-fluoro-β-d-galactopyranosyl)-(1→6)-β-d-galactopyranoside and methyl O-(3-deoxy-3-fluoro-β-d-galactopyranosyl)-(1→6)-O-β-d-galactopyranosyl-(1→6)-β-d-galactopyranoside

Condensation of 2,4,6-tri-O-acetyl-3-deoxy-3-fluoro-α-d-galactopyranosyl bromide (3) with methyl 2,3,4-tri-O-acetyl-β-d-galactopyranoside (4) gave a fully acetylated (1→6)-β-d-galactobiose fluorinated at the 3′-position which was deacetylated to give the title disaccharide. The corresponding trisaccharide was obtained by reaction of 4 with 2,3,4-tri-O-acetyl-6-O-chloroacetyl-α-d-galactopyranosyl bromide (5), dechloroacetylation of the formed methyl O-(2,3,4-tri-O-acetyl-6-O-chloroacetyl-β-d-galactopyranosyl)-(1→6)- 2,3,4-tri-O-acetyl-β-d-galactopyranoside to give methyl O-(2,3,4-tri-O-acetyl-β-d-galactopyranosyl)-(1→6)-2,3,4-tri-O-acetyl-β-d-galactopyranoside (14), condensation with 3, and deacetylation. Dechloroacetylation of methyl O-(2,3,4-tri-O-acetyl-6-O-chloroacetyl-β-d-galactopyranosyl)-(1→6)-O-(2,3,4-tri-O-acetyl- β-d-galactopyranosyl)-(1→6)-2,3,4-tri-O-acetyl-β-d-galactopyranoside, obtained by condensation of disaccharide 14 with bromide 5, was accompanied by extensive acetyl migration giving a mixture of products. These were deacetylated to give, crystalline for the first time, the methyl β-glycoside of (1→6)-β-d-galactotriose in high yield. The structures of the target compounds were confirmed by 500-MHz, 2D, ¹H- and conventional ¹³C- and ¹⁹F-n.m.r. spectroscopy.     

Acetylated allose-containing flavonoid glucosides from Stachys anisochila

In continuation of our chemosystematic study of Stachys (Labiatae) we have isolated the previously reported isoscutellarein 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-β-D-glucopyranoside] (1) and 3′-hydroxy-4′-O-methylisoscutellarein 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-β-D-glucopyranoside] (4) and four new allose-containing flavonoid glycosides from S. anisochila. The new glycosides are hypolaetin 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-β-D-glucopyranside] (6) as well as the three corresponding diacetyl analogues of 1, 4 and 6, isoscutellarein 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-6″-O-acetyl-β-D-glucopyranoside], 3′-hydroxy-4′-O-methylisoscutellarein 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-6″-O-acetyl-β-D-glucopyranoside] and hypolaetin 7-O-[6″'-O-acetyl-β-D-allopyranosyl-(1 → 2)-6″-O-acetyl-β-D-glucopyranoside]. Extensive two-dimensional NMR studies (proton-carbon correlations, COSY experiments) allowed assignment of all ¹H NMR sugar signals and a correction of the ¹³C NMR signal assignments for C-2 and C-3 of the allose.     

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 and preliminary biological evaluation of [11C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate for the fractalkine receptor (CX3CR1)

The reference standard methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate (5) and its precursor 2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucine (6) were synthesized from 6-amino-2-mercaptopyrimidin-4-ol and BnBr with overall chemical yield 7% in five steps and 4% in six steps, respectively. The target tracer [¹¹C]methyl (2-amino-5-(benzylthio)thiazolo[4,5-d]pyrimidin-7-yl)-d-leucinate ([¹¹C]5) was prepared from the acid precursor with [¹¹C]CH₃OTf through O-[¹¹C]methylation and isolated by HPLC combined with SPE in 40–50% radiochemical yield, based on [¹¹C]CO₂ and decay corrected to end of bombardment (EOB). The radiochemical purity was >99%, and the specific activity (SA) at EOB was 370–1110 GBq/μmol with a total synthesis time of ～40-min from EOB. The radioligand depletion experiment of [¹¹C]5 did not display specific binding to CX₃CR1, and the competitive binding assay of ligand 5 found much lower CX₃CR1 binding affinity.     

Steroidal saponins from the leaves of Cordyline fruticosa (L.) A. Chev. and their cytotoxic and antimicrobial activity

Three new steroidal saponins, spirosta-5,25(27)-diene-1β,3β-diol-1-O-α-l-rhamnopyranosyl-(1→2)-β-d-fucopyranoside (fruticoside H) 1, 5α-spirost-25(27)-ene-1β,3β-diol-1-O-α-l-rhamnopyranosyl-(1→2)-(4-O-sulfo)-β-d-fucopyranoside (fruticoside I) 2, and (22S)-cholest-5-ene-1β,3β,16β,22-tetrol 1-O-β-galactopyranosyl-16-O-α-l-rhamnopyranoside (fruticoside J) 3, together with the known quercetin 3-O-β-d-glucopyranoside, quercetin 3-O-[6-trans-p-coumaroyl]-β-d-glucopyranoside, quercetin 3-rutinoside, apigenin 8-C-β-d-glucopyranoside and farrerol, were isolated from the leaves of Cordyline fruticosa. Their structures were elucidated by spectroscopic techniques (¹H NMR, ¹³C NMR, HSQC, ¹H–¹H COSY, HMBC, TOCSY, NOESY), mass spectrometry (HRESIMS, Tandem MS–MS), chemical methods and by comparison with published data. Compounds 1 and 2 showed moderate cytotoxic activity against MDA-MB 231 human breast adenocarcinoma cell line, HCT 116 human colon carcinoma cell line, and A375 human malignant melanoma cell line, while compound 3 was not active. Compound 2 also showed a moderate antibacterial activity against the Gram-positive Enterococcus faecalis.     

Methylated anthocyanidin glycosides from flowers of Canna indica

Methylated anthocyanin glycosides were isolated from red Canna indica flower and identified as malvidin 3-O-(6-O-acetyl-β-d-glucopyranoside)-5-O-β-d-glucopyranoside (1), malvidin 3,5-O-β-d-diglucopyranoside (2), cyanidin-3-O-(6″-O-α-rhamnopyranosyl-β-glucopyranoside (3), cyanidin-3-O-(6″-O-α-rhamnopyranosyl)-β-galactopyranoside (4), cyanidin-3-O-β-glucopyranoside (5) and cyanidin-O-β-galactopyranoside (6) by HPLC-PDA. Their structures were subsequently determined on the basis of spectroscopic analyses, that is, ¹H NMR, ¹³C NMR, HMQC, HMBC, ESI-MS, and UV-vis. Compounds (1-4) were found to be in major quantity while compounds (5-6) were in minor quantity.     

Acyclic-sugar purine nucleosides derived from d-glucose: stereochemical correlations in acyclic-sugar derivatives unequally substituted at c-1

Condensation of 2,3,4,5,6-penta-O-acetyl-l-bromo-1-s-methyl-l-thio-d-glucito (1) with 6-chloro-9-(chloromercuri)purine gave 49% of crystalline, levorotatory (1s)-2,3,4,5,6-penta-O-acetyl-1-(6-chloropurin-9-yl)-1-s-methyl-1-thio-d-glucitol (3), together with a smaller proportion of the syrupy, dextrorotatory (1R) isomer. Thiourea converted 3 into its 6-mercaptopurine analog, whose O-deacetylated derivative could be s-methylated to the corresponding 6-(methylthio)purin-9-yl analog; all compounds in this sequence were crystalline and were the pure (1s) isomers, as were the corresponding 1′-s-ethyl derivatives prepared by a similar route. Crystal-structure analysis of the O-deacetylated derivative of the 1$\text{-}\text{?}$s-ethyl analog of 3 established the relative stereochemistry of the ethylthio group, permitting assignment of the (1s) absolute stereochemistry to this compound and thus to all compounds in the sequence starting from 1, including the previously described, crystalline, levorotatory 1-(1,6-dihydro-6-thioxopurin-9-yl)-1-s-ethyl-1-thio-d-glucitol, whose chirality at C-1 had not hitherto been established. The close similarity of the chiroptical properties of the crystalline 1′-s-methyl derivatives to those of their 1′-s-ethyl counterparts permitted firm attribution of (1s) chirality to the former series also. Conformational studies showed that all of the derivatives have the sugar chain in a non-extended (sickle) conformation.     

Photo-oxygenation of polyhydroxyalkylfurans: rearrangement of O-acetyl derivatives

The photo-oxygenation of ethyl 2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-lyxo-tetritol-1-yl)-3-furoate, ethyl 2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-arabino-tetritol-1-yl)-3-furoate, 3-acetyl-2-methyl-5-(1,2,3,4-tetra-O-acetyl-d-arabino-tetritol-1-yl)furan, and ethyl 5-(1,4-di-O-acetyl-2,3-O-isopropylidene-d-lyxo-tetritol-1-yl)-2-methyl-3-furoate yielded the corresponding 1,4-endo-peroxides (3a–3d as pairs of diastereomers). Each diastereomer of the pairs 3a and 3d was isolated by fractional crystallisation. The rearrangement of the endo-peroxides at room temperature, by dissolution in CDCl₃, yielded the corresponding diepoxides and monoepoxides. The reduction of 3a–3d with methyl sulphide yielded the corresponding γ-diketones, ethyl (E)-2-C-acetyl-5,6,7,8-tetra-O-acetyl-2,3-dideoxy-d-lyxo-oct-2-en-4-ulosonate, ethyl (E)-2-C-acetyl-5,6,7,8-tetra-O-acetyl-2,3-dideoxy-d-arabino-oct-2-en-4-ulosonate, 3-C-acetyl-6,7,8,9-tetra-O-acetyl-1,3,4-trideoxy-d-arabino-non-3-eno-2,5-diulose, and ethyl (E)-2-C-acetyl-5,8-di-O-acetyl-2,3-dideoxy-6,7-O-isopropylidene-d-lyxo-oct-2-en-4-ulosonate, which can isomerise into the corresponding Z isomers.     

Three new dinormonoterpenoid glucosides from pericarps of Myriopteron extensum

Three new dinormonoterpenoid glucosides, rel-(3R,4R)-3-(1-hydroxypropan-2-yl)-3,4-epoxypentane-1,5-diol-1-O-β-d-glucopyranoside (1), rel-(3R,4S)-3-(1-hydroxypropan-2-yl)-3,4-epoxypentane-1,5-diol-1-O-β-d-glucopyranoside (2), and rel-(3R,4S)-3-(1-hydroxy-2-propen-2-yl)-3,4-epoxypentane-1,5-diol-1-O-β-d-glucopyranoside (3), were isolated from the edible pericarps of Myriopteron extensum (Wight & Arn.) K. Schum. (Asclepiadaceae). Their structures were elucidated by chemical and spectroscopic methods including HRESIMS, 1D and 2D NMR. Dinormonoterpenoid glucosides were reported from Asclepiadaceae for the first time. Compounds 1–3 were evaluated for their cytotoxicity against five human cancer cell lines HL-60, SMMC-7221, A-549, MCF-7, and SW-480, but they did not exhibit cytotoxicity on the tested cell lines.     

Synthesis of a 6-c-nitro-d-glucopyranose derivative having phosphorus in the hemiacetal ring

5,6-Dideoxy-6-C-nitro-5-(phenylphosphino)-d-glucopyranose was prepared by addition of phenylphosphine to 3-O-acetyl-5,6-dideoxy-1,2-O-isopropylidene-6-C-nitro-α-d-xylo-hex-5-enofuranose, followed by hydrolysis of the resulting 3-O-acetyl-5,6-dideoxy-1,2-O-isopropylidene-6-C-nitro-5-(phenylphosphino)-d-glucofuranose (10). Acetylation of 10 gave the crystalline 1,2,3,4-tetraacetate (16). 5,6-Dideoxy-6-C-nitro-5-(phenylphosphinyl)-d-glucopyranose (15) was obtained by oxidation of 10, and hydrolysis of the resulting 5-phenylphosphinyl compound. Acetylation of 15 gave the 1,2,3,4-tetraacetate (17). Although the n.m.r. spectrum of 17 was complex, the n.m.r. spectrum of 16 was rather simple. The n.m.r. data showed that 16 is the α anomer in the ⁴C₁(d) conformation.     

Incorporation of privileged structures into 3-O-β-chacotriosyl ursolic acid can enhance inhibiting the entry of the H5N1 virus

The glycoprotein hemagglutinin of influenza virus plays a key role in the initial stage of virus infection, making it a potential target for novel influenza viruses entry inhibitors. Two “privileged fragments”, 2-(piperidin-1-yl)ethan-1-amine and 2-(1,3-oxazinan-3-yl)ethan-1-amine were integrated into 3-O-β-chacotriosyl ursolic acid producing new derivatives 5 and 6 with improved activity against IAVs in vitro. Mechanistically, compound 6 was effective in inhibiting infection of H1-, H3-, and H5-typed influenza A viruses by interfering with the viral hemagglutinin. Furthermore, the docking studies were in agreement with the antiviral data. These results showed that the title compound 6 as a new lead compound was meriting further optimization and development.