Divergent syntheses of all stereoisomers of phytosphingosine and their use in the construction of a ceramide library

Park, Jeong-Ju; Lee, Ji Hyung; Li, Qian; Diaz, Kristine; Chang, Young‐Tae; Chung, Sung‐Kee

doi:10.1016/j.bioorg.2007.12.004

Cited by 22 publications

(8 citation statements)

References 36 publications

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“…Theoretically these two isomers should have opposite optical rotation sign. The positive optical rotation of 3 ([α] 24 D +8 ( c 0.05, H 2 O)) favors the (2 S ,3 S ,4 R )-2-amino-1,3,4,5-pentane tetraol configuration as that of seen in l - arabino -phytosphingosine ([α] 25 D +5 ( c 0.51, pyridine)),22 which is also the opposite of that observed in d - arabino -phytosphingosine ([α] 25 D −4.3 ( c 0.50, pyridine)) 22. The identical coupling constants between H-2 and H-3 ( J = 3 Hz) and H-3 and H-4 ( J = 6 Hz) along with the optical rotation reported ([α] 27 D +9.2 ( c 0.05, MeOH)) for the sphingosine derivative12–14 and bathymodiolamides A ( 1 ) further suggested a (2 S ,3 S ,4 R )-configuration of the sphingosine-like moiety in 1 .…”

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Bathymodiolamides A and B, Ceramide Derivatives from a Deep-Sea Hydrothermal Vent Invertebrate Mussel, Bathymodiolus thermophilus

et al. 2011

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Two ceramide derivatives, bathymodiolamides A (1) and B (2), were isolated from the deep-sea hydrothermal vent invertebrate mussel Bathymodiolus thermophilus. The molecular structures of these compounds were determined using a combination of NMR spectroscopy, mass spectrometry, and chemical degradation. Biological activities were assessed in a ApopScreen cell-based screen for apoptosis induction and potential anticancer activity. To our knowledge, this is the first report of secondary metabolites from the marine hydrothermal vent mussel B. thermophilus.The oceans are the Earth's largest ecosystem and hold great, underexplored potential for drug discovery. Within this vast ecosystem, one area remains particularly enigmatic: deepsea hydrothermal vents, which are characterized by high concentrations of reduced sulfur compounds.1 Life is supported by the growth of chemolithoautotrophic bacteria, capable of oxidizing hydrogen sulfide, hydrogen, and other reduced inorganic compounds to provide energy that is used to fuel carbon dioxide fixation into macromolecules. The vent mussel Bathymodiolus thermophilus is characterized by a considerable flexibility in its sources of nutrition. Symbionts within the gills of this organism were found to be thiosulfate-and sulfide-oxidizing chemoautotrophs. In our ongoing effort to discover and develop new marine natural product biomedicinals, we have investigated the ability of the marine hydrothermal vent mussel B. thermophilus to produce novel secondary metabolites.Thirty specimens of B. thermophilus were collected using the deep submergence vehicle DSV Alvin from an active hydrothermal vent along the Mid-Atlantic Ridge, northern region, at the Lucky Strike location with a latitude of 37°17.63′ N, longitude of 32°16.53′ W, and depth of 1733 m.3 Once aboard the research vessel, the mussels were dissected, and samples of adductor muscle, gill, and mantle tissues were frozen at −70 °C for subsequent analyses. One hundred grams wet weight of the tissues from approximately 20 gills was extracted in MeOH. One part of the MeOH-soluble extract was dissolved in DMSO and was tested for apoptosis induction as assessed by the ApopScreen protocol.4 -6 Screening was expected to identify compounds that possess proapoptotic, and potentially anticancer, activity.The extract induced apoptosis and therefore was fractionated, with subsequent purification by analytical reversed-phase HPLC. Using this strategy, two compounds were isolated. The chemical structures of these two compounds (1 and 2) were ascertained by standard spectroscopic techniques, as described below. . Analysis of the multiplicity-edited HSQC spectrum for 1 revealed that these heteroatom-substituted carbons comprise two methylenes (CH 2 -1, δ C 63.7, δ H 3.65; CH 2 -5, δ C 59.9, δ H5a 4.20, δ H5b 4.45) and three methines (CH-2, δ C 53.5, δ H 4.29; CH-3, δ C 62.5, δ H 4.01; CH-4, δ C 66.1, δ H 5.25). The HMBC correlations between H-2 and the carbonyl at δ C 173.2, H-4 and the carbonyl at δ C 173.4, and H-5a and H-5b and the ca...

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Bathymodiolamides A and B, Ceramide Derivatives from a Deep-Sea Hydrothermal Vent Invertebrate Mussel, Bathymodiolus thermophilus

et al. 2011

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“…18 The azide group was reduced under the Staudinger conditions, 19 and the resulting amine ( 19–22 ) was efficiently acylated with four different N -hydroxysuccinimide activated esters. 20 In the final step all benzyl protecting groups were removed with H 2 over Pd(OH) 2 /C to yield 16 analogues ( 1–4 ) of α-GalCer (Scheme 2). …”

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Syntheses and biological activities of KRN7000 analogues having aromatic residues in the acyl and backbone chains with varying stereochemistry

Park

Lee

Seo

et al. 2010

Bioorganic & Medicinal Chemistry Letters

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KRN7000 is an important ligand identified for CD1d protein of APC, and KRN7000/CD1d complex can stimulate NKT cells to release a broad range of bioactive cytokines. In an effort to understand the structure–activity relationships, we have carried out syntheses of 26 new KRN7000 analogues incorporating aromatic residues in either or both side chains. Structural variations of the phytosphingosine moiety also include varying stereochemistry at C3 and C4, and 4-deoxy and 3,4-dideoxy versions. Their biological activities are described.

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“…Sphingolipids are a diverse class of lipids that are composed of free sphingoid bases and their phosphates, ceramides and sphingomyelins, as well as complex glycosphingolipids [59]. Many of these lipids are well-known signaling molecules that have been implicated in various diseases, including metabolic disorders [60] and cancer [61].…”

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confidence: 99%

Metabolic Profile Changes of CCl4-Liver Fibrosis and Inhibitory Effects of Jiaqi Ganxian Granule

Wang

et al. 2016

Molecules

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Jiaqi Ganxian Granule (JGG) is a famous traditional Chinese medicine, which has been long used in clinical practice for treating liver fibrosis. However, the mechanism underlying its anti-hepatic fibrosis is still not clear. In this study, an Ultra-Performance Liquid Chromatography-Time-Of-Flight Mass Spectrometry (UPLC-TOF-MS)-based metabolomics strategy was used to profile the metabolic characteristic of serum obtained from a carbon tetrachloride (CCl 4 )-induced hepatic fibrosis model in Sprague-Dawley (SD) rats with JGG treatment. Through Principal Component Analysis (PCA) and Partial Least Square Discriminant Analysis (PLS-DA), it was shown that metabolic perturbations induced by CCl 4 were inhibited after treatment of JGG, for 17 different metabolites related to CCl 4 . Among these compounds, the change tendency of eight potential drug targets was restored after the intervention with JGG. The current study indicates that JGG has a significant anti-fibrosis effect on CCl 4 -induced liver fibrosis in rats, which might be by regulating the dysfunction of sphingolipid metabolism, glycerophospholipid metabolism, N-acylethanolamine biosynthesis, fat digestion and absorption, while glycerophospholipid metabolism played vital roles in the inhibitory effects of JGG on hepatic fibrosis according to Metabolic Pathway Analysis (MetPA). Our findings indicated that the metabolomics approach may provide a useful tool for exploring potential biomarkers involved in hepatic fibrosis and elucidate the mechanisms underlying the action of therapies used in traditional Chinese medicine.

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Divergent syntheses of all stereoisomers of phytosphingosine and their use in the construction of a ceramide library

Cited by 22 publications

References 36 publications

Bathymodiolamides A and B, Ceramide Derivatives from a Deep-Sea Hydrothermal Vent Invertebrate Mussel, Bathymodiolus thermophilus

Bathymodiolamides A and B, Ceramide Derivatives from a Deep-Sea Hydrothermal Vent Invertebrate Mussel, Bathymodiolus thermophilus

Syntheses and biological activities of KRN7000 analogues having aromatic residues in the acyl and backbone chains with varying stereochemistry

Metabolic Profile Changes of CCl4-Liver Fibrosis and Inhibitory Effects of Jiaqi Ganxian Granule

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