Xanthones from the bark of Garcinia pedunculata

Three new xanthones, pedunxanthones A–C (1–3), together with five known compounds, 1,5-dihydroxy-3-methoxy-6′,6′-dimethyl-2H-pyrano(2′,3′:6,7)-4-(3-methylbut-2-enyl)xanthone, 1,5-dihydroxy-3-methoxy-4-(3-methylbut-2-enyl)xanthone, dulxanthone A, garbogiol and oleanolic acid, were obtained from a petroleum ether extract of the bark of Garcinia pedunculata. The new structures were elucidated using spectroscopic methods, mainly 1-D and 2-D NMR.     

Synthesis of 6,1′,6′-tri-O-(mesitylenesulfonyl)sucrose,further examination of “tri-O-tosylsucrose”, and the chemistry of 3,6:1′,4′:3′,6′-trianhydrosucrose

Selective trimolar mesitylenesulfonylation of sucrose resulted in the formation of a highly crystalline trimesitylenesulfonate (1), which was isolated in greater than 50% yield without recourse to chromatography. As anticipated, the sulfonyl groups in 1 were located at the primary positions, as treatment with alkali afforded 3,6:1′,4′:3′,6′-trianhydrosucrose (4) in high yield. Fractionation of “tri-O-tosylsucrose” by high-pressure liquid chromatography effected separation of the minor isomer from the known, preponderant 6,1′,6′-isomer 3. ¹³C-N.m.r. spectroscopy indicated that the minor isomer was 2,6,6′-tri-O-p-tolylsulfonylsucrose (2). The trianhydride 4 was found to be dimorphous and was further characterized as the diacetate (5), the dibenzoate (6), the di-p-toluenesulfonate (7), and the dimethyl ether (8). Considerable differences in the reactivities toward acylation and etherification of the two axial hydroxyl groups in 4 permitted the preparation, in good yields, of the 4-acetate (9) and the 4-methyl ether (12). Several derivatives of methyl 3,6-anhydro-α-d-glucopyranoside (13) were prepared for comparison with corresponding derivatives of 4, and the hydroxyl groups in 13 also showed differences in reactivities analogous with those of 4.     

Two new dihydrobenzofuran-type neolignans from Breynia fruticosa

(7S,8R,7′S)-9,7′,9′-Trihydroxy-3,4-methylenedioxy-3′-methoxy [7-O-4′,8-5′] neolignan (1) and (7S,8R,7′S)-9,9′-dihydroxy-3,4-methylenedioxy-3′,7′-dimethoxy [7-O-4′,8-5′] neolignan (2), two new natural dihydrobenzofuran-type neolignans, along with 9,9′-dihydroxy-3,4-methylenedioxy-3′-methoxy [7-O-4′,8-5′] neolignan (3) and (-)-machicendiol (4), were isolated from the whole plants of Breynia fruticosa. The structures of 1 and 2, including the absolute configurations, were determined by spectroscopic methods and circular dichroism (CD) techniques. The absolute configuration of 4 was confirmed by calculations of the OR spectrum, together with OR and ECD spectra of its p-bromobenzoate ester (4a).     

Reaction of methanesulphonyl chloride-N,N-dimethylformamide with partially esterified derivatives of sucrose

Treatment of sucrose 2,3,3′,4′,6-penta-acetate (1) with methanesulphonyl chloride-N,N-dimethylformamide (reagent A) gave the 1′,4,6′-trichloride 2, the 1′-O-formyl-4,6′-dichloride 3, the 4,6′-dichloride 4, and the 1′,4-di-O-formyl-6′-chloride 5. De-esterification of 3 afforded the unsubstituted 4,6′-dichloride 6 which, on acetylation, gave the corresponding hexa-acetate 7, also prepared by acetylation of 4. In compounds 2, 3, and 4, substitution at C-4 by chloride ion occurred with inversion of configuration. The structure of 5 was confirmed by conversion into the known 6′chloro-6′-deoxysucrose hepta-acetate by de-esterification followed by acetylation. Treatment of sucrose 1′,2,3,3′,4′,6′-hexa-acetate (10) with the reagent gave the 4,6-dichloride 11 and 4-O-formyl-6-chloride 12. The formyl group in 12 was selectively removed by using an anion-exchange resin to give 16. De-esterification of 12 with methanolic sodium methoxide gave 6-chloro-6-deoxysucrose (13) which, on acetylation and benzoylation, afforded the hepta-acetate 14 and the hepta-benzoate 15, respectively. Alternatively, 15 was prepared by the reaction of 1′,2,3,3′,4,4′,6′-hepta-O-benzoylsucrose with reagent A. Treatment of 14 with sodium methoxide in methanol followed by acetylation gave 3,6-anhydrosucrose hexa-acetate (24). Reaction of sucrose 2,3,3′,4,4′-pentabenzoate (17) with reagent A gave the known 1′,6,6′-trichloro-1′,6,6′-trideoxysucrose pentabenzoate (18) and 1′-O-formyl-6,6′-dichloride 19. Treatment of 19 with anion-exchange resins selectively removed the formyl group to give 20. The structure of 20 was confirmed by conversion into the 1′-chlorosulphate-6,6′-dichloride (21). Treatment of sucrose 1′,2,3,3′,4,4′-hexabenzoate (22) with reagent A gave the expected 6,6′-dichloride (23).     

Monohydroxycarotenoids from diphenylamine-inhibited cultures of Rhodospirillum rubrum

The monohydroxycarotenoids formed by diphenylamine-inhibited cultures of Rhodospirillum rubrum have been investigated. Nine have been isolated and identified as 1-hydroxy-1,2-dihydrophytofluene (1), 1-Hydroxy-1,2,7′,8′,11′,12′-hexahydrolycopene (2), chloroxanthin (3), 1-methoxy-1′-hydroxy-1,2,1′,2′-tetrahydrophytofluene (4a), 1′-hydroxy-3,4,1′,2′,11′,12′-hexahydrospheroidene (5, 1′-hydroxy-3,4,1′,2′-tetrahydrospheroidene (6, 1′-hydroxy 1′,2′-dihydrospheroidene (7), rhodovibrin (8a) and monodeme thylated spirilloxanthin (9). 4a, 5 and 6 are novel carotenoids, and a definite structure has been assigned to 2 for the first time; the structure of 1 has been amended. The possible role of these carotenoids in spirilloxanthin biosynthesis is discussed.     

A convenient synthesis of 6′-C-substituted β-maltose heptaacetates and of panose

Benzylidenation of β-maltose monohydrate with α,α-dimethoxytoluene in N,N-dimethylformamide in the presence of p-toluenesulfonic acid gave, in 70% yield, 4′,6′-O-benzylidenemaltose, which was acetylated to afford, 1,2,3,6,2′,3′-hexa-O-acetyl-4′,6′-O-benzylidene-β-maltose (4). Removal of the benzylidene group of 4 gave 1,2,3,6,2′,3′-hexa-O-acetyl-β-maltose (5), which was transformed into 1,2,3,6,2′,3′,4′-hepta-O-acetyl-6′-O-p-tolylsulfonyl-β-maltose (8). Several 6′-substituted β-maltose heptaacetates were synthesized by displacement reactions of 8 with various nucleophiles. Condensation of 5 with 2,3,4,6-tetra-O-benzyl-α-d-glucopyranosyl bromide, under catalysis by halide ion, followed by removal of protecting groups, furnished panose in good yield.     

Three new neolignan glucosides from the stems of Dendrobium aurantiacum var. denneanum

Three new neolignan glucosides (1–3), together with four known analogs (4–7), have been isolated from the stems of Dendrobium aurantiacum var. denneanum. Structures of the new compounds including the absolute configurations were determined by spectroscopic and chemical methods as (−)-(8R,7′E)-4-hydroxy-3,3′,5,5′-tetramethoxy-8,4′-oxyneolign-7′-ene-9,9′-diol 4,9-bis-O-β-d-glucopyranoside (1), (−)-(8S,7′E)-4-hydroxy-3,3′,5,5′-tetramethoxy-8,4′-oxyneolign-7′-ene-9,9′-diol 4,9-bis-O-β-d-glucopyranoside (2), and (−)-(8R,7′E)-4-hydroxy-3,3′,5,5′,9′-pentamethoxy-8,4′-oxyneolign-7′-ene-9-ol 4,9-bis-O-β-d-glucopyranoside (3), respectively.     

Lignan glycosides from the Rhizomes of Smilax trinervula and their Biological activities

Phytochemical investigation of the rhizomes of Smilax trinervula led to isolation and structure elucidation of eight lignan glycosides, including five new lignans, namely, (7S, 8R, 8′R)-4, 4′, 9-trihydroxy-3, 3′, 5, 5′-tetramethoxy-7, 9′-epoxylignan-7′-one 4′-O-β-d-glucopyranoside (1), (7S, 8R, 8′R)-4, 4′, 9-trihydroxy-3, 3′, 5, 5′-tetramethoxy-7, 9′-epoxylignan-7′-one 4-O-β-d- glucopyranoside (2) (7S, 8R)-4, 9, 9′-trihydroxy-3, 3′, 5-trimethoxy-4′, 7-epoxy-8, 5′-neolignan 9′-O-β-d-glucopyranoside (3), (7R, 8R)-4, 9, 9′-trihydroxy-3, 5-dimethoxy-7.O.4′, 8.O.3′- neolignan 9′-O-β-d-glucopyranoside (4), and (7S, 8R)-4, 9, 9′-trihydroxy-3, 3′, 5-trimethoxy-8, 4′-oxy-neolignan 4-O-β-d-glucopyranoside (5), along with three known compounds (6-8). Their structures were established mainly on the basis of 1D and 2D NMR spectral data, ESI–MS and comparison with the literature. Compounds 1-8 were tested in vitro for their cytotoxic activity against four human tumor cell lines (SH-SY5Y, SGC-7901, HCT-116, Lovo). Compounds 3 and 5 exhibited cytotoxic activity against Lovo cells, with IC₅₀ value of 10.4 μM and 8.5 μM, respectively.     

Synthesis of derivatives of methyl β-sophoroside

Selective tritylation of methyl β-sophoroside (1) and subsequent acetylation gave the 3,4,2′,3′,4′-penta-O-acetyl-6,6′-di-O-trityl derivative, which was O-detritylated, and the product p-toluenesulfonylated, to give methyl 3,4,2′,3′,4′-penta-O-acetyl-6,6′-di-O-p-tolylsulfonyl-β-sophoroside (4) in 63% net yield. Compound 4 was also obtained in 69% yield by p-toluenesulfonylation of 1, followed by acetylation. Several, 6,6′-disubstituted derivatives of 1 were synthesized by displacement reactions of 4 with various nucleophiles. Treatment of 4 with sodium methoxide afforded methyl 3,6:3′,6′-dianhydro-β-sophoroside. Several 6- and 6′-monosubstituted derivatives of 1 were prepared, starting from the 4,6-O-benzylidene derivative of 1.     

Synthesis of sucrose epoxides,partial de-esterification of 1′,2:4,6-di-O-isopropylidenesucrose tetra-acetate,and selective tosylation of 3,6′-di-O-acetyl-1′,2:4,6-di-O-isopropylidenesucrose

Selective de-esterification of 1′,2:4,6-di-O-isopropylidenesucrose tetra-acetate² (1) with methanolic ammonia at ?10° gave an inseparable mixture (2+3) of the 3,4′,6′- and 3,3′,6′-triacetates and also the 4,6′-diacetate 4. When the reaction was performed at 5°, it gave 4, the 4-acetate 8, and the parent diacetal 9. These derivatives allow selective reaction at hydroxyl groups in sucrose, in particular at HO-3′ and, HO-4′, not hitherto possible. Mesylation of 4 gave the 3′,4′-dimesylate 7, which, on treatment with aqueous acetic acid followed by acetylation, afforded 3′,4′-di-O-mesylsucrose hexa-acetate (11). Treatment of 11 with sodium methoxide in methanol at 70° for 1 min gave the ribo-3′,4′-epoxide 12 as the minor, and the lyxo-3′,4′-epoxide 13 as the major, product. Selective tosylation of 4 gave the 3',4'-ditosylate 14 (3.7%), 4′-tosylate 15 (3.1%), and 3'-tosylate 16 (31%), indicating the order of reactivity HO-3′>HO-4′ in 4. De acetalation of 15 and 16 followed by acetylation gave the hepta-acetates of 4′- and 3′-O-tosylsucrose, respectively, which were converted into the respective epoxides, 13 and 12, by methanolic sodium methoxide.     

The first replacement of a chlorosulphonyloxy group by chlorine at C-2 in methyl α-D-glucopyranoside and sucrose derivatives

Treatment of methyl 3-O-acetyl-4,6-O-benzylidene-α-D-glucopyranoside 2-chlorosulphate (2), 3,4,6,3′,4′,6′-hexa-O-acetylsucrose 2,1′-bis(chlorosulphate), 3,4,6,3′,4′,6′-hexa-O-acetyl-1′-O-benzoylsucrose 2-chlorosulphate, and 3,4,3′,4′-tetra-O-acetyl-6,6′-dichloro-6,6′-dideoxysucrose 2,1′-bis(chlorosulphate) with lithium chloride in hexamethylphosphoric triamide gave the corresponding chlorodeoxy-manno derivatives. Treatment of the 2-chlorosulphate 2 with such nucleophilic reagents as lithium bromide, sodium azide, sodium chloride, and sodium benzoate in hexamethylphosphoric triamide gave the 2-hydroxy compound as a major product. Selective chlorination at C-1′ was achieved when 3,4,6,3′,4′,6′-hexa-O-acetylsucrose was treated with sulphuryl chloride in a mixture of pyridine and chloroform.     

The synthesis of 4′,6′-diacetamido-4′,6′-dideoxycellobiose hexa-acetate from lactose

Reaction of methyl 4′,6′-di-O-mesyl-β-lactoside pentabenzoate (8), synthesised via the 4′,6′-O-benzylidene derivative (6), with sodium azide in hexamethylphosphoric triamide gave three products. In addition to the required 4′,6′-diazidocellobioside (9), an elimination product, methyl 4-O-(6-azido-2,3-di-O-benzoyl-4,6-dideoxy-α-L-threo-hex-4-enopyranosyl)-2,3,6-tri-O-benzoyl-β-D-glucopyranoside (12), and an unexpected product of interglycosidic cleavage, methyl 2,3,6-tri-O-benzoyl-β-D-glucopyranoside (13), were formed. The origin of the latter product is discussed. The diazide 9 was converted into 4′,6′-diacetamido-4′,6′-dideoxycellobiose hexa-acetate (16) by sequential debenzoylation, catalytic reduction, acetylation, and acetolysis.     

Derivatives of β-D-fructofuranosyl α-D-galactopyranoside

De-etherification of 6,6′-di-O-tritylsucrose hexa-acetate (2) with boiling, aqueous acetic acid caused 4→6 acetyl migration and gave a syrupy hexa-acetate 14, characterised as the 4,6′-dimethanesulphonate 15. Reaction of 2,3,3′4′,6-penta-O-acetylsucrose (5) with trityl chloride in pyridine gave a mixture containing the 1′,6′-diether 6 the 6′-ether 9, confirming the lower reactivity of HO-1′ to tritylation. Subsequent mesylation, detritylation, acetylation afforded the corresponding 4-methanesulphonate 8 1′,4-dimethanesulphonate 11. Reaction of these sulphonates with benzoate, azide, bromide, and chloride anions afforded derivatives of β-D-fructofuranosyl α-D-galactopyranoside (29) by inversion of configuration at C-4. Treatment of the 4,6′-diol 14 the 1,′4,6′-triol 5, the 4-hydroxy 1′,6′-diether 6 with sulphuryl chloride effected replacement of the free hydroxyl groups and gave the corresponding, crystalline chlorodeoxy derivatives. The same 4-chloro-4-deoxy derivative was isolated when the 4-hydroxy-1′,6′-diether 6 was treated with mesyl chloride in N,N-dimethylformamide.     

Flavonoids from Artemisia ludoviciana var. ludoviciana

Nineteen flavonoids were isolated from Artemisia ludoviciana var. ludoviciana, including a new 2′- hydroxy- 6-methoxyflavone, 5,7,2′,4′-tetrahydroxy-6,5′-dimethoxyflavone. The known compounds include quercetagetin 3,6,3′,4′-tetramethyl ether, eupatilin, 5,7-dihydroxy-3,6,8,4′-tetramethoxyflavone, luteolin 3′,4′-dimethyl ether, jaceosidin, 5,7,4′-trihydroxy-3,6-dimethoxyflavone, tricin, hispidulin, chrysoeriol, kaempferol 3-methyl ether, apigenin, axillarin, eupafolin, selagin and luteolin together with three flavones which were previously isolated for the first time from Artemisia frigida: 5,7,4′-trihydroxy-6, 3′,5′-trimethoxyflavone, 5,7,3′-trihydroxy-6,4′,5′-trimethoxyflavone and 5,7,3′,4′-tetrahydroxy-6,5′- dimethoxyflavone.     

Some observations on the selective benzoylation of maltose and its derivatives

Benzoylation of β-maltose monohydrate (2) with 10 mol. equiv. of benzoyl chloride in pyridine at ?40° gave 1,2,6-tri-O-benzoyl-4-O-(2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl)-β-D-glucopyranose (5) in 87% yield, without the need for column chromatography. Similarly, benzoylation of 2 with 8 mol. equiv. of reagent afforded the octabenzoate 5, and the 1,2,6,2′,3′,6′-hexabenzoate 11 in 3%, 79%, and 12% yield, respectively. Methyl 2,6,2′,3′,4′,6′-hexa-O-benzoyl-β-maltoside (10) was directly isolated as a crystalline monoethanolate in 83% yield, from the reaction mixture obtained by the benzoylation of methyl β-maltoside monohydrate (8) with 8.9 mol. equiv. of reagent. Benzoylation of 8 with 7 mol. equiv. of reagent produced 10 and the 2,6,2′,3′,6′-pentabenzoate 16 in 71% and 23% yield, respectively. The order of reactivity of the hydroxyl groups in methyl 4′,6′-O-benzylidene-β-maltoside towards benzoylation is HO-2, HO-6>HO-2′ ≈ HO-3′>HO-3. Benzoylation of methyl β-cellobioside (33) with 7.9 mol. equiv. of reagent gave the heptabenzoate and the 2,6,2′,3′,4′,6′-hexabenzoate 36 in 56% and 27% yield, respectively. Compounds 5, 16, and 36 were transformed into 4-O-α-D-glucopyranosyl-D-allopyranose, methyl 4-O-α-D-galactopyranosyl-β-D-allopyranoside, and methyl 4-O-β-D-glucopyranosyl-β-D-allopyranoside, respectively, by sequential sulfonylation, nucleophilic displacement, and O-debenzoylation.     

Enzymatic regioselective and complete deacetylation of two arabinonucleosides

Candida antarctica lipase B (CAL-B)-catalysed regioselective deacetylation of 2′,3′,5′-tri-O-acetyl-1-β-d-arabinofuranosyluracil (1) and 2′,3′,5′-tri-O-acetyl-9-β-d-arabinofuranosyladenine (2) was studied. The choice of the reaction medium allowed the regioselective formation of products bearing different degree of acetylation: in isopropanol, CAL-B catalysed the formation of the corresponding 2′-O-acetylated arabinonucleosides, while hydrolyses afforded the 2′,3′-di-O-acetylated products. In particular, the procedure herein described allows a simple and efficient preparation of the reported vidarabine prodrug 2′,3′-di-O-acetyl-9-β-d-arabinofuranosyladenine, avoiding the utilisation of protective groups. Moreover, to achieve full deacetylation of the assayed substrates, a set of commercial hydrolases and fungal keratinases from Doratomyces microsporus (DMK) and Paecilomyces marquandii (PMK) were tested. While only PMK and DMK catalysed the quantitative complete deacetylation of 1, DMK accomplished full deacetylation of 2 in shorter time than the other assayed enzymes.     

Discrimination between the 2,3- and the 2′,3′-hydroxyl groups of maltose and cellobiose through their specific protection

1,6-Anhydro-4′,6′-O-benzylidene-maltose and -cellobiose were subjected to temporary O-protection with a tetraisopropyldisiloxane-1,3-diyl group at the 2′,3′- and the 2,3-positions, giving 1,6-anhydro-4′,6′-O-benzylidene-2′,3′-O-(tetraisopropyldisiloxane- 1,3-diyl)maltose (15) and 1,6-anhydro-4′,6′-O-benzylidene-2,3- O-(tetraisopropyldisiloxane-1,3-diyl)cellobiose (19), respectively, in 60–64% yield. These were then subjected to various types of O-protection fo the hydroxyl groups remaining. Treatment of 15 and 19 with acetic anhydride or phenyl isocyanate gave the corresponding diacetyl and dicarbamoyl derivatives in high yield. Benzylation of the maltose derivative 15 was rather difficult, but was finally achieved through a phase-transfer reaction, to give the 2,3-di-O-benzyl derivative (18) in moderate yield. In the cellobiose series, benzylation of 19 was conducted similarly, giving 22, and also by employing a modification of the conventional procedure. The silyl groups of 18 and 22 were removed by treatment with tetrabutylammonium fluoride, to afford the corresponding diols in high yield.     

Chemotaxonomic significance of lignans from Serissa japonica (Thunb.) Thunb

Sixteen known lignans were isolated from the 95% alcohol extract of the whole plant of Serissa japonica (Thunb.) Thunb., including nine furofurans (1–9), three tetrahydrofurans (10–12) and four arylnaphthalenes (13–16). In the present report, compounds (+)-epipinoresinol (1), (+)-1-hydroxy-6-epipinoresinol 4,4″-di-O-methyl ether (3), (−)-pinoresinol (4), (+)-8-hydroxypinoresinol (6), pseuderesinol (7), (+)-1-hydroxysyringaresinol (8), (−)-(7′S,8S,8′R)-4,4′-dihydroxy-3,3′,5,5′-tetramethoxy-7′,9-epoxylignan-9′-ol-7-one (10), wikstrone (11), 7'-(+)-oxomatairesinol (12), (+)-cycloolivil (13), (+)-isolariciresinol (14), 5-methoxy-(+)-isolariciresinol (15) and cyclolignans (16) were reported from the Serissa genus for the first time, and compounds (+)-lirioresinol A (2) and (−)-lirioresinol B (5) were firstly isolated from the plant. Their structures were elucidated on the basis of extensive spectroscopic and chemical analyses. Moreover, the chemotaxonomic significance of the isolated compounds is discussed.     

Myricetin and quercetin methyl ethers from Haplopappus integerrimus var. Punctatus

Nine flavonoids including two new myricetin derivatives, myricetin 3′,4′-dimethyl ether and myricetin 3,3′, 4′-trimethyl ether, were obtained from Haplopappus integerrimus var. punctatus. The known compounds are quercetin 7,3′-dimethyl ether, querectin 3,3′-dimethyl ether, isorhamnetin, quercetin 3,7-dimethyl ether, quercetin 3-methyl ether, quercetin and quercetin 3-β-d-glucoside.     

Synthesis and antimicrobial activities of halogenated bis(hydroxyphenyl)methanes

A series of halophenols was prepared by the reaction of bis(hydroxyphenyl)methanes with effective halogenating agents such as bromine and sulfuryl chloride. One of these compounds, a biologically active halophenol—2,2′,3,3′-tetrabromo-4,4′,5,5′-tetrahydroxydiphenylmethane (1)—frequently isolated from red algae, was synthesized for the first time. Other halophenols included several novel compounds, together with known derivatives that were synthesized from the phenolic intermediates, bis(3,4-dihydroxyphenyl)methane (5) and bis(2-hydroxyphenyl)methane (14). All of the synthesized compounds were tested for antimicrobial activity against Gram-positive, Gram-negative bacteria and fungi. The preliminary structure–activity relationship was investigated in order to determine the essential structural requirements for their antimicrobial activity. Of all these halophenols, 2,2′,3,3′,6-pentabromo-4,4′,5,5′-tetrahydroxydiphenylmethane (8) was found to be the most active against Candida albicans, Aspergillus fumigatus, Trichophyton rubrum, and Trichophyton mentagrophytes while 3,3′,5,5′-tetrachloro-2,2′-dihydroxydiphenylmethane (18) exerted a powerful antibacterial effect against Staphylococcus aureus, Bacillus subtilis, Micrococcus luteus, Proteus vulgaris, and Salmonella typhimurium.