Studies on dehydro-l-ascorbic acid 3-oxime 2-phenylhydrazone: Conversion into substituted triazoles

l-threo-2,3-Hexodiulosono-1,4-lactone 3-oxime 2-(phenylhydrazone) (1) gave 2-(p-bromophenyl)-4-(l-threo-1,2,3-trihydroxypropyl)-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone (2), and this gave a diacetyl and a dibenzoyl derivative. On treatment of 2 with liquid ammonia, methylamine, or dimethylamine, the corresponding triazole-5-carboxamides (5–7) were obtained. Periodate oxidation of 5 gave 2-(p-bromophenyl)-4-formyl-1,2,3-triazole-5-carboxamide (10), and, on reduction, 10 gave 2-(p-bromophenyl)-4-(hydroxymethyl)-1,2,3-triazole-5-carboxamide, characterized as its monoacetate. Condensation of 10 with phenylhydrazine gave the triazole hydrazone. Acetonation of 2 gave the isopropylidene derivative. Reaction of 2 with HBr-HOAc gave 4-(l-threo-2-O-acetyl-3-bromo-1,2-dihydroxypropyl)-2-(p-bromophenyl)-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone. Similar treatment of 1 with HBr-HOAc gave 5-O-acetyl-5-bromo-6-deoxy-l-threo-2,3-hexodiulosono-1,4-lactone 3-oxime 2-(phenylhydrazone). This was converted into 4-(l-threo-2-O-acetyl-3-bromo-1,2-dihydroxypropyl)-2-phenyl-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone on treatment with boiling acetic anhydride. On reaction of 1 with benzoyl chloride in pyridine, dehydrative cyclization occurred, with the formation of 4-(l-threo-2,3-dibenzoyloxy-1-hydroxypropyl)-2-phenyl-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone, which was converted into the amide on treatment with ammonia.     

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.     

Terpenoid metabolites from the aerial part of Artemisia lagocephala

Six naturally occurring terpenoids were isolated from the hexane extract of rabbit-head wormwood Artemisia lagocephala (Fisch. ex Besser) DC. The terpenoids’ structures were elucidated by spectroscopic and chemical methods as 3β-acetoxycycloartan-24-ozonide (1), 3β-acetoxycycloartan-24-al (2), 25,26,27-trisnor-3β-acetoxycycloartan-24-ol (3), 24,25,26,27-tetranor-3β-acetoxycycloartan-23-ol (4), and the previously known caryophyllene oxide (5) and (1R,4S)-p-menth-2-en-1-ol (6).     

Facile synthesis and rearrangement of L-threo-2,3-hexodiulosono-1,4-lactone 2-(2-arylhydrazones)

Controlled reaction of L-threo-2,3-hexodiulosono-1,4-lactone with substituted phenylhydrazines gave the 2-(monoarylhydrazones) (2), which underwent dehydrative acetylation to 4-(2-acetoxyethylidene)-4-hydroxy-2,3-dioxohutyro-1,4-lactone 2-(2-arylhydrazones) (3). The latter reacted with methylhydrazine to give 1-methyl-3-(1-methylpyrazolin-3-yl)-4,5-pyrazoledione 4-(2-arylhydrazones) (4). Reaction of the monoarythydrazones (2) with phenylhydrazine gave the mixed bishydrazones (5), which were rearranged by alkali and acidification to the pyrazolediones (6). Compounds 6 gave triacetyl (7) and tribenzoyl derivatives (8), and, on periodite oxidation, the aldehydes (9), which afforded the monohydrazones (10). The i.r.. n.m.r.. and mass-spectral data of some of the compounds were investigated.     

Sesquiterpenoids from Pilea cavaleriei subsp. crenata

Three new humulane-type sesquiterpenes, 8-O-(p-coumaroyl)-5β-hydroperoxy-1(10)E,4(15)-humuladien-8α-ol (1), 8-O-(3-nitro-p-coumaroyl)-1(10)E,4(15)-humuladien-5β,8α-diol (2) and 8-O-(p-coumaroyl)-1(10)E,4(5)E-humuladien-8-ol (3), and a new copaborneol derivative, 1-O-p-coumaroyl-copaborneol (4), have been isolated from the methanol extract of Pilea cavaleriei Lévl. subsp. crenata C. J. Chen. Their structures were elucidated using spectroscopic methods. Cytotoxic and antimicrobial activities of the isolated compounds were evaluated.     

On the ring transformation of hydrazine derivatives of l-ascorbic acid into nitrogen heterocyclic derivatives

l-hreo-2,3-hexodiulosono-1,4-lactone 2-(p-methoxyphenylhydrazone) (1) was condensed with arylhydrazines to give mixed bishydrazones, whose acetylation gave the corresponding di-O-acetyl derivatives. The hydrazone 1 undergoes elimination of one molecule of water per molecule during, the acetylation, and gives 4-(2-acetoxy- ethylidene)-4-hydroxy-2,3-dioxobutano-1,4-lactone 2-(p-methoxyphenylhydrazone), which reacts with methylhydrazine, via a ring transformation process, to give 1-methyl-3-(L-methylpyrazolin-3-yl)-4,5-pyrazoledione 4-(p-methoxyphenylhydrazone). Alkali rearranged the mixed bishydrazones to 1-aryl-3-(l-threo-glycerol-1-yl)-4,5- pyrazoledione 4-(p-methoxyphenylhydrazones), which gave triacetyl and tribenzoyl derivatives, and, upon periodate oxidation, afforded 1-aryl-3-formyl-4,5- pyrazolediones 4-(p-methoxyphenylhydrazones) that gave the corresponding phenylhydrazones. The n.m.r. and mass spectra of some of these derivatives have been investigated.     

Studies on dehydro-d-arabino-ascorbic acid 2-arylhydrazone 3-oximes: Conversion into substituted triazoles and isoxazolines

d-erythro-2,3-Hexodiulosono-1,4-lactone 2-arylhydrazones (2) were prepared by condensation of dehydro-d-arabino-ascorbic acid with the desired arylhydrazine. Reaction of 2 with hydroxylamine gave the 2-arylhydrazone 3-oximes (3). On boiling with acetic anhydride, 3 gave 2-aryl-4-(2,3-di-O-acetyl-d-erythro-glycerol-1-yl)-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone (5), whereas the unacetylated triazole derivatives were obtained upon reaction of 3 with bromine in water. On treatment of 5 with hydrazine hydrate, 2-aryl-4-(d-erythro-glycerol-1-yl)-1,2,3-triazole-5-carboxylic acid 5-hydrazides (6) were obtained. Acetylation of 6 gave the hexaacetyl derivatives. Similarly, treatment of 5 with liquid ammonia gave the triazolecarboxamides (12). Vigorous acetylation of 12 with boiling acetic anhydride gave tetraacetates, whereas acetylation with acetic anhydride-pyridine gave triacetates. Periodate oxidation of 6 gave the 2-aryl-4-formyl-1,2,3-triazole-5-carboxylic acid 5-hydrazides (8), and, on reduction, 8 gave the 2-aryl-4-(hydroxymethyl)-1,2,3-triazole-5-carboxylic acid 5-hydrazides, characterized as acetates. Similarly, periodate oxidation of 12 gave the triazolealdehyde (15), and reduction of 15 gave the hydroxymethyl derivatives (16). Acetylation of 16 gave the mono- and di-acetates, and, on reaction with o-phenylenediamine, 15 afforded the triazoleimidazole. Controlled reaction of 3 with sodium hydroxide, followed by neutralization, gave 3-(d-erythro-glycerol-1-yl)-4,5-isoxazolinedione 4-arylhydrazones. Reaction of 3 with HBr-HOAc gave 5-O-acetyl-6-bromo-6-deoxy-d-erythro-2,3-hexodiulosono-1,4-lactone 2-arylhydrazone 3-oximes (21). Compounds 21 were converted into 4-(2-O-acetyl-3-bromo-3-deoxy-d-erythro-glycerol-1-yl)-2-aryl-1,2,3-triazole-5-carboxylic acid 5,1¹-lactone on treatment with acetic anhydride.     

Studies on dehydro-l-ascorbic acid 2-arylhydrazone 3-oximes: Conversion into substituted triazoles and isoxazolines

l-threo-2,3-Hexodiulosono-1,4-lactone 2-(arylhydrazones) (2) were prepared by condensation of dehydro-l-ascorbic acid with various arylhydrazines. Reaction of 2 with hydroxylamine gave the 2-(arylhydrazone) 3-oximes (3). On boiling with acetic anhydride, 3 gave 2-aryl-4-(2,3-di-O-acetyl-l-threo-glycerol-l-yl)-1,2,3-triazole-5-carboxylic acid 5,4¹-lactones (4). On treatment of 4 with liquid ammonia, 2-aryl-4-(l-threo-glycerol-l-yl)-1,2,3-triazole-5-carboxamides (5) were obtained. Acetylation of 5 with acetic anhydride-pyridine gave the triacetates, and vigorous acetylation with boiling acetic anhydride gave the tetraacetyl derivatives. Periodate oxidation of 5 gave the 2-aryl-4-formyl-1,2,3-triazole-5-carboxamides (8), and, on reduction, 8 gave the 2-aryl-4-(hydroxymethyl)-1,2,3-triazole-5-carboxamides, characterized as the monoacetates and diacetates. Controlled reaction of 2 with sodium hydroxide, followed by neutralization, gave 3-(l-threo-glycerol-l-yl)-4,5-isoxazolinedione 4-(arylhydrazones), characterized by their triacetates. Reaction of 2 with HBr-HOAc gave 5-O-acetyl-6-bromo-6-deoxy-l-threo-2,3-hexodiulosono-1,4-lactone 2-(arylhydrazones); these were converted into 4-(2-O-acetyl-3-bromo-3-deoxy-l-threo-glycerol-l-yl)-2-aryl-1,2,3-triazole-5-carboxylic acid 5,4¹-lactones on treatment with acetic anhydride-pyridine.     

Cooperative aspects of hydrogen bonding in carbohydrates

Various compounds related to the antibacterial, sulfanilamide drugs have been prepared from dehydro-l-ascorbic acid or its d-erythro analog by reaction with hydrazines related to sulfanilamide, sulfadiazine, sulfamerazine, sulfamethazine, and sulfamethoxydiazine, whereby the 2-mono- and 2,3-bis-(hydrazone) were isolated. After opening of the lactone ring in the bis(hydrazones) with alkali, nucleophilic attack, on the carbonyl group, of the imino nitrogen atom of the 3-hydrazone residue afforded 3-(l-threo-glycerol-1-yl)-1-phenyl- and -1-(p-sulfamylphenyl)-4,5-pyrazole-dione 4-(p-sulfamylphenlhydrazone) and the related 3-(d-erythro-glycerol-1-yl)compounds. Whereas acetylation of l-threo-2,3-hexodiulosono-1,4-lactone 2,3-bis(p-sulfamylphenylhydrazone) (9) and 3-(l-threo-glycerol-1-yl)-1-(p-sulfamylphenyl)-4,5-pyrazoledione 4-(p-sulfamylphenylhydrazone) (15) gave the O-acetyl derivatives, benzoylation of 15 gave the di-N-benzoy ltri-O-benzoyl compound. Reaction of 9 with cupric chloride gave 3,6-anhydro-3-(p-suIfamylphenylazo) -l-xylo-2-hexulosono-1,4-lactone 2-(p-sulfamylphenylhydrazone). The 3-(l-threo-glycerol-1-yl)-1-(p-sulfamylphenyl)flavazole (35) was prepared by the rearrangement of 3-[(1-p-sulfamylphenyl)hydrazono-l-threo-trihydroxybutyl]-2-quinoxalinont (33). Periodate oxidation of 15,33, and 35 gave 3-formyl-1-(p-sulfamylphenyl)-4,5-pyrazoledione 4-(p-sulfamylphenylhydrazone), 3-1-[(p-sulfamylphenyl)hydrazono]glyoxal-1-yl]-2-quinoxalinone, and 3-formyl-1-(p-sulfamylphenyl)flavazole, respectively. The i.r. and n.m.r. spectral data for some of these derivatives are reported.     

Synthesis of 2.3-unsaturated polysaccharides from amylose and xylan

Amylose (1) was tritylated at O-6, the ether p-toluenesulfonylated at O-2 and O-3, and the product (3) treated with sodium iodide and zinc dust in N,N-dimethyl-formamide, to give 2,3-dideoxy-6-O-trityl-α-D-erythro-hex-2-enopyranoglycan (4). This 2,3-unsaturated polysaccharide could be converted into a 2,3-dibromo derivative (5), and hydrogenated with concomitant detritylation to the saturated analogue (6), and, on treatment with aqueous acetic acid, it gave 2-(D-glycero-1,2-dihydroxyethyl)-furan (8). The 2,3-bis(p-toluenesulfonate) (10) of β-D-xylan (9) was similarly converted into the 2,3-unsaturated polysaccharide, 2,3-dideoxy-β-D-glycero-pent-2-enopyranoglycan (11), which, with aqueous acetic acid, gave 2-(hydroxymethyl)furan (12a).     

Some studies on dehydro-d-ascorbic acid 2-(phenylhydrazone)

Reaction of hydroxylamine with d-erythro-2,3-hexodiulosono-1, 4-lactone 2-(phenylhydrazone) (2) gave the 3-oxime 2-(phenylhydrazone) (3). On boiling with acetic anhydride, 3 gave 4-(d-erythro-2,3-diacetoxy-l-hydroxypropyl)-2-phenyl-1,2, 3-triazoIe-5-carboxylic acid 5,1′-lactone. Compound 3 was also converted into the related, unacetylated 2-(p-bromophenyl)triazole with bromine. Treatment of 2 with boiling acetic anhydride gave an optically inactive, olefinic compound, assigned the structure 4-(2-acetoxyethylidene)-4-hydroxy-2,3-dioxobutano-1,4-lactone 2-(phenylhydrazone). The 2-(phenylhydrazone) 2 gave the corresponding 2,3-bis(phenylhydrazone) on condensation with phenylhydrazine.     

Diarylheptanoids from Curcuma comosa

Three new diarylheptanoids, designated 1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-(6E)-6-hepten-3-ol (1), 1-(3-hydroxyphenyl)-7-(3,4-dihydroxyphenyl)-3-methoxy-(6E)-6-heptene (2), (3R, 5R)-1-(3,4-dihydroxyphenyl)-7-phenyl-heptane-3,5-diol (3) and three known compounds, were isolated from rhizomes of Curcuma comosa. Structures of the compounds were determined by spectroscopic data analysis.     

β-elimination in aldonolactones. Synthesis of 2-deoxy-D-lyxo-hexose and 2-deoxy-D-arabino-hexose

Benzoylation of D-glycero-L-manno-heptono-1,4-lactone (1) with benzoyl chloride and pyridine for 2 h afforded crystalline penta-O-benzoyl-D-glycero-L-manno-heptono-1,4-lactone (2), but a large excess of reagent during 8 h also led to 2,5,6,7-tetra-O- benzoyl-3-deoxy-D-lyxo-hept-2-enono-1,4-lactone (3). Catalytic hydrogenation of 3 was stereoselective and gave 2,5,6,7-tetra-O-benzoyl-3-deoxy-D-galacto-heptono-1,4-lactone (4). Debenzoylation of 4 followed by oxidative decarboxylation with ceric sulfate in aqueous sulfuric acid gave 2-deoxy-D-lyxo-hexose (5). Application of the same reaction to 3-deoxy-D-gluco-heptono-1,4-lactone afforded 2-deoxy-D-arabino-hexose (6).     

Cytotoxicity of new polyfluorinated 1,4-naphtoquinones with diverse substituents in the quinone moiety

Fluorinated derivatives of 1,4-naphthoquinones are highly potent inhibitors of Cdc25A and Cdc25B phosphatases and growth of tumor cells. Eight new derivatives of polyfluoro-1,4-naphthoquinone were synthesized and their cytotoxicity in human myeloma, human mammary adenocarcinoma, mouse fibroblasts and primary mouse fibroblast cells as well as their mutagenic and antioxidant properties in a Salmonella tester strain were studied. The efficiency of suppressing the growth of two lines of tumor cells decreased in the order: 2-(2-hydroxy-ethylamino)-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (1), 2,3-dimethoxy-5,6,7,8-tetrafluoro-1,4-naphthoquinone (2), 2-[2-hydroxyethyl(methyl)amino]-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (3), 2-morpholino-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (4), 2-[bis-(2-hydroxyethyl)amino]-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (5), 2-[(2-hydroxy)ethylsulfanyl)]-5,6,7,8-tetrafluoro-1,4-naphthoquinone (6), 2-methoxy-3,5,6,7,8-pentafluoro-1,4-naphthoquinone (7), and 1,4-dioxo-3-(1-pyridinio)-1,4-dihydro-5,6,7,8-tetrafluoronaphthalene-2-olate (8). Taking into account these data together with the better cytotoxic effect against cancer cells as compared with normal mammalian cells, protecting of bacterial cells from spontaneous and H₂O₂-dependent mutagenesis, and lower general toxicity of the compounds towards different cells, one can propose that compounds 3-5 may be considered as useful potential inhibitors of growth of tumor cells.     

Enzymatic synthesis of poly-N-acetyllactosamines as potential substrates for endo-β-galactosidase-catalyzed hydrolytic and transglycosylation reactions

Enzymatic synthesis of GlcNAc-terminated poly-N-acetyllactosamine β-glycosides GlcNAcβ1,3(Galβ1,4GlcNAcβ1,3)_nGalβ1,4GlcNAcβ-pNP (n=1–4) was demonstrated using a transglycosylation reaction of Escherichia freundii endo-β-galactosidase. The enzyme catalyzed a transglycosylation reaction on GlcNAcβ1,3Galβ1,4GlcNAcβ-pNP (1), which served both as a donor and an acceptor, and converted 1 into p-nitrophenyl β-glycosides GlcNAcβ1,3(Galβ1,4GlcNAcβ1,3)₁Galβ1,4GlcNAcβ-pNP (2), GlcNAcβ1,3(Galβ1,4GlcNAcβ1,3)₂Galβ1,4GlcNAcβ-pNP (3), GlcNAcβ1,3(Galβ1,4GlcNAcβ1,3)₃Galβ1,4GlcNAcβ-pNP (4) and GlcNAcβ1,3(Galβ1,4GlcNAcβ1,3)₄Galβ1,4GlcNAcβ-pNP (5). When 2 was used as an initial substrate, it led to the preferential synthesis of nonasaccharide β-glycoside 4 to heptasaccharide β-glycoside 3. This suggests that 4 is directly synthesized by transferring the tetrasaccharide unit GlcNAcβ1,3Galβ1,4GlcNAcβ1,3Gal to nonreducing end GlcNAc residue of 2 itself. The efficiency of production of poly-N-acetyllactosamines by E. freundii endo-β-galactosidase was significantly enhanced by the addition of BSA and by a low-temperature condition. Resulting 2 and 3 were shown to be useful for studying endo-β-galactosidase-catalyzed hydrolytic and transglycosylation reactions.     

Synthesis of branched-chain sugar derivatives related to aldgarose

Ethynylation of 1,2:5,6-di-O-isopropylidene-α-D-ribo-hexofuranos-3-ulose (1) gave the 3-C-ethynyl allo derivative 2, together with an adduct (3) resulting from interaction of two molecules of 1 with one of acetylene. Lithium aluminum hydride reduced the acetylenes 2 and 3 to the corresponding alkenes 4 and 8; on sequential ozonolysis-borohydride reduction, these both gave 3-C-(hydroxymethyl)-1,2:5,6-di- O-isopropylidene-α-D-allofuranose (6), further characterized as its 3,3¹-cyclic carbonate 9. Ozonolysis of the acetylene 2 gave the 3¹,5-lactone (5) of the 3-C-carboxy analog, thus establishing the stereochemistry of 2, which was independently established by n.m.r. spectroscopy employing a lanthanide shift-reagent. Treatment of 2 with mercuric acetate in ethyl acetate, followed by hydrogen sulfide, gave a mixture of the 3-C-acetyl-3-O-acetyl derivative 10 and a product (11) derived from internal cyclization of 5,6-deacetonated, O-deacetylated 10. Reduction of 10 with lithium aluminum hydride gave a separable mixture of diastereoisomeric 3-C-(l-hydroxy-ethyl) derivatives (12a, 12b) that were individually converted into their corresponding 3,3¹-cyclic carbonates 13a and 13b, products that contain the branch functionality of the unusual, branched-chain sugar aldgarose.     

Four analogues of spiroleptosphol isolated from Leptosphaeria doliolum

Spiroleptosphol B (2), spiroleptosphol C (3), norleptosphol C (4) and hydroleptosphol (5) were isolated from ascomycete Leptosphaeria doliolum. Detailed ¹H and ¹³C NMR spectral analyses revealed these were structural analogues of spiroleptosphol (1) which we have recently isolated from the same fungi. Spiroleptosphol B (2) carried an unprecedent 5,3-dioxatricyclo[4.4.0.1^1.4]undecane framework in place of the spirobicyclo ring system of 1. Spiroleptosphol C (3) was a 17-(R)-hydroxy derivative of 1. Norleptosphol C (4) was deduced to be the monocyclic structure biosynthetically resulted by decarboxylation from 3. Although 5 gave broaden ¹H NMR spectrum, it was gradually transformed to 2 which suggested being a hydrolysate of 1.     

Diarylpentanoids from Diplomorpha canescens and Diplomorpha ganpi

Two new α-hydroxy ketone type diarylpentanoids, diplomorphanone A, 2(S)-hydroxy-1-(4-hydroxyphenyl)-5-phenyl-1-pentanone (1) and diplomorphanone B, 2(R)-hydroxy-1,5-diphenyl-1-pentanone (2) were isolated from aerial parts of Diplomorpha canescens (Meisn.) C.A. Meyer and roots of Diplomorpha ganpi (Sieb. et Zucc.) Nakai, respectively. Nine known compounds including diarylpentanoids (3–6), phenylpropanoid derivatives (7–9), (+)-afzelechin (10) and apiosylskimmin (11) were also isolated for the first time from D. ganpi. Structures of these compounds were elucidated on the basis of spectroscopic data.     

The synthesis of new deoxynitroinositols by cyclization of 6-deoxy-3-O-methyl-6-nitro-d-allose and -l-talose

6-Deoxy-3-O-methyl-6-nitro-d-allose (5) and -l-talose (6) were synthesized from 1,2-O-isopropylidene-3O-methyl-α-d-allofuranose (1) by the nitromethane method via their furanoid, 1,2-O-isopropylidene derivatives (2 and 3). The barium hydroxide-catalyzed cyclization of the free nitrohexoses (5 and 6) was investigated. Under conditions favoring kinetic control (pH ～8, 0°), 5 gave mainly 1d-5-deoxy-2-O-methyl-5-nitro-allo-inositol (7), with the 1l-epi-1 (8) and epi-6 (9) stereoisomers as minor products. Compound 6 afforded a high yield of the myo-5-isomer (11); the 1l-allo-5 (13) and 1d-epi-1 (14) isomers were formed in small proportions but not isolated. The thermodynamically controlled, mutual interconversion of the stereoisomeric products was studied, as was the formation of nitronate salts and the regeneration of free nitroinositols. Upon immediate acidification, the nitronate obtained from 11 gave 11 and the neo-2 epimer (12) in a ratio of 2:3. The nitronate produced by 7 underwent rapid β-epimerization. The five isolated deoxynitroinositol monomethyl ethers were further characterized as tetra-acetates (7a, 9a, 11a, and 12a) and isopropylidene derivatives (7b, 8b, and 9b).     

Rothmanniamide and other constituents from the leaves of Rothmannia hispida (K.Schum.) fagerl. (Rubiaceae) and their chemophenetic significance

The chemical investigation of the CH₂Cl₂/MeOH (1:1) extract of the leaves of Rothmannia hispida (K. Schum.) Fagerl. (Rubiaceae) led to the isolation of a new ceramide rothmanniamide (1) and a naturally isolated alkyl cinnamate derivative n-heptadecyl-4-hydroxy-trans-cinnamate (2), along with fifteen known compounds including lupeol palmitate (3), lupeol (4), a mixture of uvaol (5) and erythrodiol (6), ursolic acid (7), 30-nor-2α,3β-dihydroxyurs-12-ene (8), hederagenin (9), stigmast-22-en-3-ol (10), a mixture of β-sitosterol (11) and stigmasterol (12), stigmast-4,22-dien-3-ol (13), stigmasterol 3-O-β-D-glucoside (14), triacontan-1-ol (15), kaempferol 3-O-β-D-glucopyranoside (16) and D-mannitol (17). Their structures were elucidated with the help of MS and NMR data. Compounds 8, 10 and 15 were isolated for the first time from the Rubiaceae family. The crude extract and the isolates were assessed in vitro for their antileishmanial activity against Leishmania donovani 1 S (MHOM/SD/62/1 S) promastigotes and cytotoxicity on RAW 264.7 macrophage cells. Compounds 7 and 8 exhibited a highly potent antileishmanial activity with IC₅₀ values of 0.88 and 1.75 μg/mL, respectively, with good selectivity indexes (SI > 57). The chemophenetic significance of these compounds is also discussed.