Two new ceramides from the stems of Piper betle L.

<正>Two new ceramides,(2S,3S,4R)-2-N-[(2'R)-2'-hydroxypentacosanoylamino]-nonacosane-1,3,4-triol(1) and(2S,3S,4R,8E)-2- N-[(2'R)-2'-hydroxytetracosanoylamino]-8-eicosylene-1,3,4-triol(2) have been isolated from the stems of Piper betle L.collected from Baoshan city of Yunnan Province in China.Their structures were determined by spectroscopic and chemical methods.     

Isolation and structure of four new ceramides from the starfish Luidia maculata

A new sphingosine-type ceramide LMCer-1-1 (1) and three new phytosphingosine-type ceramides, LMCer-2-1 (2), LMCer-2-6 (3), and LMCer-2-7 (4), were isolated from the anti-hyperglycemic active ceramide molecular species LMCer-1 and LMCer-2, obtained from the less polar fraction of the chloroform-methanol extract of the whole bodies of Luidia maculata. The structures of these ceramides were determined on the basis of chemical and spectroscopic evidence as: (2S,3R,4E,2'R)-2-(2-hydroxyhexadecanoylamino)-16-methyl-4-octadecene-1,3-diol (1), (2S,3S,4R,2'R)-2-(2-hydroxyhexadecanoylamino)-16-methyl-octadecane-1,3,4-triol (2), (2S,3S,4R,2'R)-2-(2-hydroxydocosanoylamino)-hexadecane-1,3,4-triol (3), and (2S,3S,4R,2'R)-2-(2-hydroxydocosanoylamino)-14-methyl-hexadecane-1,3,4-triol (4).     

Ceramide constituents from five mushrooms

Five mushrooms, Panellus serotinus, Lyophyllum connatum, Amanita pantherina, Sarcodon aspratus and Lepista nuda, have been investigated chemically. Two new ceramides, (2S,3R,4E,8E)-N-hexadecanoyl-2-amino-9-methyl-4,8-octadecadiene-1,3-diol (1) and (2S,3R,4E,8E,9'Z,12'Z)-N-9',12'-octadecadienoyl-2-amino-9-methyl-4,8-octadecadiene-1,3-diol (2), have been isolated from Panellus serotinus. Compound 2 was also isolated from Lyophyllum connatum. Two new ceramides, (2S,2'R,3R,4E,8E)-N-2'-hydroxypentadecanoyl-2-amino-9-methyl-4,8-octadecadiene-1,3-diol (4) and (2S,2'R,3R,4E,8E)-N-2'-hydroxytetradecanoyl-2-amino-9-methyl-4,8-octadeca-diene-1,3-diol (5), have been isolated from Amanita pantherina with (2S,2'R,3R,4E,8E)-N-2'-hydroxyhexadecanoyl-2-amino-9-methyl-4,8-octadecadiene-1,3-diol (3), a known synthetic compound. Compounds 3 and 4 were also isolated from Sarcodon aspratus and compound 3 was isolated from Lepista nuda. The structures of the new compounds were elucidated on the basis of their spectral data.     

Amphimelibiosides A-F, six new ceramide dihexosides isolated from a Japanese marine sponge Amphimedon sp

Six new ceramide dihexosides, amphimelibiosides A-F (1-6), were isolated from a Japanese marine sponge Amphimedon sp. The structure of amphimelibioside C (3), which is a major component of amphimelibiosides, was determined by 2D NMR techniques, chemical degradation, and a semisynthetic method to be 1-O-[beta-D-glucopyranosyl-(1-->6)-alpha-D-galactopyranosyl]-(2S,3S,4R,6E)-2-[(2'R)-2-hydroxydocosanoyl]-2-amino-6-octadecene-1,3,4-triol. The structures of the other constituents were elucidated by a combination of mass spectra, (1)H NMR, and GC-MS analysis.     

Structures of new ceramides from the fruit bodies of Grifola frondosa

Four new phytosphingosine-type ceramides, (2S,3S,4R)-2-[(2'R)-2'-hydroxydocosanoylamino]-1,3,4-octadecane triol (1), (2S,3S,4R)-2-[(2'R)-2'-hydroxytricosanoylamino]-1,3,4-octadecan etriol (2), (2S,3S,4R)-2-[(2'R)-2'-hydroxypentacosanoylamino]-1,3,4-octadec anetriol (3) and (2S,3S,4R)-2-[(2'R)-2'-hydroxyhexacosanoylamino]-1,3,4-octadeca netriol (4), have been isolated from the fruit bodies of Grifola frondosa. The structures of the new compounds were elucidated on the basis of their spectral data.     

New sphingolipids and a sterol from a lobophytum species of the Indian ocean

Chemical investigation of a soft coral species of the genus Lobophytum has resulted in the isolation of three new sphingolipids--(2S,3S,4R)-2-nonadecanoylamino-octadecane-1,3,4-triol (1), (2S,3R,4E,8E)-[(2'R)-2'-hydroxyheptadecanoylamino]-4,8-octadecadiene-1,3-diol (2), 1-O-(beta-D-glucopyranosyl)-(2S,3R,4E,8E)-2-[(2'R)-2'-hydroxynonadecanoylamino]-9-methyl-4,8-octadecadiene-1,3-diol (3) and a sterol--(24S)-ergost-5-en-3beta,7beta-diol (4) along with the known sphingolipid--(2S,3R,4E,8E)-2-hexadecanoylamino-4,8-octadecadien-1,3-diol (5) which showed cytotoxicity against human peripheral blood mononuclear cells (PBMC).     

New cytotoxic cerebroside from Gynura divaricata

A new cerebroside,gynuraoside(1),was isolated from the aerial parts of Gynura divaricata DC.It was determined to be 1-O-β- D-glucopyranosyl-(2S,3S,4R,10E)-2-[(2′R)-2′-hydroxyldocosanoyl-amino]-10-octadecene-1,3,4-triol on the basis of chemical and spectroscopic evidence.This compound showed strong cytotoxicity against L1210 leukemia cell line in vitro.     

Cerebrosides from the roots of Serratula chinensis

A new cerebroside, 1-O-beta-D-glucopyranosyl-(2S,3R,8E)-2-[(2'R)-2-hydroxy- palmitoylamino]-8-octadecene-1,3-diol, along with aralia cerebroside and 1-O-beta-D- glucopyranosyl-(2S,3S,4R,8E)-2-[(2'R)-2-hydroxybehenoylamino]-8-octadecene-1,3,4-triol were isolated from the roots of Serratula chinensis S. Moore. The structure of the new cerebroside was established by spectroscopic and chemical means. Occurrence of cerebrosides in Serratula is reported here for the first time.     

Antimicrobial activity of sphingolipids isolated from the stems of cucumber (Cucumis sativus L.)

Three antimicrobial sphingolipids were separated by bioassay-guided isolation from the chloroform fraction of the crude methanol extract of cucumber (Cucumis sativus L.) stems and identified as (2S,3S,4R,10E)-2-[(2'R)-2-hydroxytetra-cosanoylamino]-1,3,4-octadecanetriol-10-ene (1), 1-O-β-D-glucopyranosyl(2S,3S,4R,10E)-2-[(2'R)-2-hydroxy-tetracosanoylamino]-1,3,4-octadecanetriol-10-ene (2) and soya-cerebroside I (3) by their physicochemical properties and spectroscopic analysis. They were evaluated to show antifungal and antibacterial activity on test microorganisms including four fungal and three bacterial species. Among them, compound 1, a relatively low polarity aglycone, exhibited stronger antimicrobial activity than its corresponding glycoside 2. The results indicated that sphingolipids could be the main antimicrobial compounds in the crude methanol extract of cucumber stems.     

Antibacterial sphingolipid and steroids from the black coral Antipathes dichotoma

From the black coral Antipathies dichotoma, a sphingolipid (2S*,3S*,4E,8E)-2N-[tetradecanoyl]-4(E),8(E)-icosadiene-1,3-diol (1) and a steroid (22E)-methylcholesta-5,22-diene-1α,3β,7α-triol (2) were isolated. Other known compounds, 3β,7α-dihydroxy-cholest-5-ene (3), (22E,24S),5α,8α-epidioxy-24-methylcholesta-6,22-dien-3β-ol (4) and (22E,24S),5α,8α-epidioxy-24-methylcholesta-6,9(11),22-trien-3β-ol (5). The structures were established on the basis of NMR spectroscopic analysis and comparison with literature. The antibacterial activity of five compounds was evaluated.     

New glycosides from the Japanese fern Hymenophyllum barbatum

Thirteen glycosides and methyl (3R,5R)-5-hydroxy-(beta-D-glucopyranosyloxy)-hexanoate were newly isolated from the Japanese fern Hymenophyllum barbatum, although our previous work revealed the isolation of hemiterpene glycosides, hymenosides A-J, from the same species. The structures of the newly isolated glycosides were elucidated by extensive two-dimensional (2D) NMR and/or chemical evidence. The structures of those aglycones were divided into four types, 2-methyl-but-2-ene-1,4-diol, 2-hydroxymethyl-but-2-ene-1,4-diol, 2-methylene-butane-1,3,4-triol, and 3-hydroxy-5-hexanolide. The sugar moieties, which were acylated by phenylacetic acid derivatives, were also established by chemical and spectroscopic methods. Eight glucosides of the isolated compounds in the present investigation had a bitter or weakly pungent taste. It is clear that a phenylacetyl group attached to glucose or allose as an ester is necessary for the bitter taste.     

Cyclooxygenase-2 inhibitory cerebrosides from phytolaccae radix

A mixture of cerebrosides, called poke-weed cerebrosides, was purified from Phytolaccae Radix (Phytolaccaceae) and characterized as 1-O-beta-D-glucopyranosides of phytosphingosine type ceramides comprised of a common long chain base (2S,3S,4R,8Z)-2-amino-8-octadecene-1,3,4-triol and fatty acids. The fatty acyl chain of ceramide moieties was determined as (2R)-2-hydroxypentacosanoic acid, (2R)-2-hydroxylignoceric acid, (2R)-2-hydroxytricosanoic acid, (2R)-2-hydroxybehenic acid, (2R)-2-hydroxypalmitic acid, and palmitic acid. The pokeweed cerebroside inhibited the cyclooxygenase-2 dependent phase of prostaglandin D2 generation in bone marrow-derived mast cells in a concentration dependent manner with an IC50 of 6.2 microg/ml.     

Sesquiterpenoid derivatives from Ferula ferulaeoides [correction of ferulioides]. V

Nine novel prenyl-dihydrofurocoumarin-type sesquiterpenoid derivatives, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4-methyl-5- (4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo-[3,2-c]coumarin, and 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, were isolated from the roots of Ferula ferulaeoides [corrected]. The structures were established by comprehensive spectral analysis. The biosynthetic pathway leading to these prenyl-furocoumarin-type sesquiterpenoids is proposed based on their structures.     

A stereodivergent,two-directional synthesis of stereoisomeric C-linked disaccharide mimetics

Dipyranones, such as 1,2-bis[(2R,3S,6S)-3-hydroxy-6-methoxy-3-oxo-6H-pyran-2-yl]ethane, were exploited as templates for the synthesis of some novel C-linked disaccharide analogues. Efficient methods, such as stereoselective reduction and dihydroxylation, were developed for two-directional functionalisation of these templates. Peracetylated derivatives of ten stereoisomeric disaccharide analogues [acetic acid 4,5-diacetoxy-6-methoxy-[(3',4',5'-triacetoxy-6'-methoxytetrahydropyran- 2'-yl)ethyl]tetrahydropyran-3-yl esters] were synthesised from a virtual library of 136 compounds; furthermore, an additional eight stereoisomers could have been synthesised simply by using the enantiomeric ligand in the enantioselective step. The ability of (2S,3S,4R,5R,6R)-6-methoxy-2-[2'-((2'R,3'R,4'S, 5'R,6'S)-3',4',5'-trihydroxy-6'-methoxytetrahydropyran-2'-yl) ethyl]tetrahydropyran-3,4,5-triol to bind to the repressor protein, LacI, was estimated to be similar to that of isopropyl-beta-thiogalactoside. The disaccharide mimetics were concluded to be a new and interesting class of C-linked disaccharide mimetics with promising, though largely unstudied, biological activity.     

Total syntheses of symbioramide derivatives from l-serine and their antileukemic activities

Naturally occurring symbioramide, (2S,3R,2'R,3'E)-N-(2'-hydroxy-3'-octadecenoyl)-dihydrosphingosine 1a, was synthesized from d-erythro-dihydrosphingosine (amino part, 2) and (2R,3E)-2-hydroxy-3-octadecenoic acid (acid part, 3a), both of which were prepared from l-serine. Its diastereomer, (2S,3R,2'S,3'E)-1b, having an enantiomer of the unnatural-type acid part that was prepared from d-mannitol, and its corresponding (Z)-isomers, (2S,3R,2'R,3'Z)-1c and (2S,3R,2'S,3'Z)-1d, were also prepared. The antileukemic activities of 1a-d against HL-60 and L-1210 cells were appreciated by a MTT assay. None of the four symbioramide derivatives showed antileukemic activities in HL-60 cells. In L-1210 cells, all the symbioramide derivatives showed moderate antileukemic activities. Compound 1d had the most effective activity against L-1210 cells among the four derivatives. The data suggest that unnatural types of (2'S)-isomers of acid parts are more active than those of (2'R)-isomers.     

Triterpene glycosides of Thalictrum squarrosum. III. Structures of squarrogenins 1 and 2

Two genins — squarrogenin 1 and squarrogenin 2 — have been isolated from nodding meadow rue by the hydrolysis of squarrosides A1 and A2. The compounds are epimeric at C-21 and have the following structures: 1 — (21R, 22S, 23R)-21-methoxy-21,23-epoxycycloart-24-ene-3β,22β-30-triol, C₃₁H₅₀O₅, mp 169–171°C (hexane-acetone), [α] ₅₄₆ ²⁰ ?11.06° (c 4.52; pyridine); and 2 — (21S, 22S, 23R)-21-methoxy-21,23-epoxycycloart-24-ene-3β,22β,30-triol, C₃₁H₅₀O₅, mp 190–193°C (hexane-acetone), [α] ₅₄₆ ²⁰ +106.6° (c 0.3; pyridine). The results of¹H and¹³C NMR spectroscopy and of mass spectrometry for the new compounds are given.     

远东疣柄牛肝菌的化学成分

从远东疣柄牛肝菌(Leccinum extremiorientale)子实体中提取分离得到13个 化合物，通过理化常数和波谱数据分析，它们的结构被鉴定为：麦角甾-7，22-二 烯-3β，5α，6β-三醇（1），麦角甾醇过氧化物（2），麦角甾醇（3），麦角甾 -4，6，8（14），22-四烯-3-酮（4），麦角甾-5，7-二烯-3β-醇（5），棕榈酸 （6），（2S，3S，4R，2’R）-2-（2’-羟基二十四碳酰胺）十八烷-1，3，4-三 醇（7），脑苷脂B（8），脑苷脂D（9），尿嘧啶（10），肌苷（11），腺苷（12 ），D-阿洛醇（13），利用2D NMR（~1H-~1H COSY，HMBC，HMQC）技术首次对化合 物8和9的氢谱和碳谱数据进行了全归属。在浓度为100 μg/mL时，化合物2，7和8 表现出选择性地抗蛇毒Crotalus adamenteus分泌的磷脂酶A_2活性，而对蜂毒 Apis mellifcra磷脂酶A_2却无活性。此外，远东疣柄牛肝菌提取物对粘虫拒食率 和小莱蛾死亡率分别为67%和55%。     

A convergent approach to the marine natural product eleutherobin: synthesis of key intermediates and attempts to produce the basic skeleton

Synthesis of (1R,5R,6R)-2-(6-hydroxymethyl-5-isopropyl-2-methylcyclohex-2-enyl)-N- methoxy-N-methylacetamide 8 from R-(-)-phellandrene in six steps, and (3aR*,4S*,6R*,6aS*)- (6-hydroxymethyl-4-methoxy-2,2,6-trimethyltetrahydrofuro[3,4-d][1,3]dioxol- 4-yl)acetic acid methyl ester 17 from tetrabromoacetone and 2-methoxy-5-methylfuran in six steps, provided two key fragments which have been combined to produce intermediates for attempted construction of the basic skeleton of eleutherobin.     

A potent bicyclic inhibitor of a family 27 alpha-galactosidase

Two isomeric bicyclo[4.1.0]heptane analogues of the glycosidase inhibitor galacto-validamine, (1R*,2S,3S,4S,5S,6S*)-5-amino-1-(hydroxymethyl)bicyclo[4.1.0]heptane-2,3,4-triol, have been synthesized in 13 steps from 2,3,4,6-tetra-O-benzyl-D-galactose. The inhibitory activities of the two conformationally restricted amines, and their corresponding acetamides, were measured against commercial alpha-galactosidase enzymes from coffee bean and E. coli. The activity of the glycosyl hydrolase family GH27 enzyme (coffee bean) was competitively inhibited by the 1R,6S-amine (7), a binding interaction that was characterized by a K(i) value of 0.541 microM. The GH36 E. coli alpha-galactosidase exhibited a much weaker binding interaction with the 1R,6S-amine (IC(50)= 80 microM). The diastereomeric 1S,6R-amine (9) bound weakly to both galactosidases, (coffee bean, IC(50)= 286 microM) and (E. coli, IC(50)= 2.46 mM).     

Anti-inflammatory and antioxidant components from Hygroryza aristata

Twenty-six known compounds and two new compounds, including a new lignan, (7S*,8R*,7'R*,8'S*)-icariol A?-9-O-β-xylopyranoside (1), and a new indole alkaloid, hygarine (2), were isolated from the extracts of Hygroryza aristata (Gramineae). The structures of all compounds were elucidated on the basis of NMR spectral analysis. The compounds (-)-epigallocatechin-3-O-gallate (4) and (-)-epicatechin-3-O-gallate (5) possess free radical scavenging activities and compound 1 could inhibit superoxide anion generation and elastase release by fMLP/CB-induced human neutrophils with IC?? values of 19.33 ± 0.86 and 24.14 ± 1.59 μM, respectively.