- Fellutamides A and B, cytotoxic peptides from a marine fish-possessing fungus Penicillium fellutanum
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Two cytotoxic peptides, fellutamides A and B, have been isolated from the cultured fungus Penicillium fellutanum Biourge which was isolated from the gastrointestine of the marine fish Apogon endekataenia Bleeker, and the structures were elucidated to be 1 and 2 by two-dimensional NMR and FAB MS/MS data.
- Shigemori,Wakuri,Yazawa,Nakamura,Sasaki,Kobayashi
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- Enzymatic Regio- And Enantioselective C-H Oxyfunctionalization of Fatty Acids
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Directed evolution of a P450 hydroxylase (P450BSβ) achieves an engineered enzyme that is able to catalyze C-H oxyfunctionalization of fatty acids (FAs) in a highly regio- and enantioselective fashion (>20:1 Cβ/Cα and > 99% ee in all cases). The biocatalyst displays high reactivity (TON up to 1540), takes inexpensive H2O2 as oxidant, and converts C11-C18 saturated FAs as well as naturally derived unsaturated oleic and linoleic acids to optically pure β-hydroxy FAs. Merging biocatalysis with chemical transformation, we further offer a chemoenzymatic strategy to access valuable FA derivatives bearing 1,3-diol, β-amino, β-lactone, and β-lactam functionalities in either enantiomeric form. Molecular docking studies provide a rationale for the regio- and enantioselectivity of this reaction.
- Chen, Hao,Huang, Mengfei,Yan, Wenliang,Bai, Wen-Ju,Wang, Xiqing
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p. 10625 - 10630
(2021/09/02)
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- Enantioselective organocatalysis-based synthesis of 3-hydroxy fatty acids and fatty γ-lactones
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3-Hydroxy fatty acids have attracted the interest of researchers, since some of them may interact with free fatty acid receptors more effectively than their non-hydroxylated counterparts and their determination in plasma provides diagnostic information regarding mitochondrial deficiency. We present here the development of a convenient and general methodology for the asymmetric synthesis of 3-hydroxy fatty acids. The enantioselective organocatalytic synthesis of terminal epoxides, starting from long chain aldehydes, is the key-step of our methodology, followed by ring opening with vinylmagnesium bromide. Ozonolysis and subsequent oxidation leads to the target products. MacMillan’s third generation imidazolidinone organocatalyst has been employed for the epoxide formation, ensuring products in high enantiomeric purity. Furthermore, a route for the incorporation of deuterium on the carbon atom carrying the hydroxy group was developed allowing the synthesis of deuterated derivatives, which may be useful in biological studies and in mass spectrometry studies. In addition, the synthesis of fatty γ-lactones, corresponding to 4-hydroxy fatty acids, was also explored.
- Bourboula, Asimina,Limnios, Dimitris,Kokotou, Maroula G.,Mountanea, Olga G.,Kokotos, George
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- Correction: Total synthesis of fellutamides, lipopeptide proteasome inhibitors. More sustainable peptide bond formation (Organic and Biomolecular Chemistry (2016) 14 (8367-8375)
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The incorrect graphics for Schemes 3 and 4 were included. The correct schemes are shown below. (Figure Presented). The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.
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p. 9159 - 9159
(2016/10/11)
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- Total synthesis of fellutamides, lipopeptide proteasome inhibitors. More sustainable peptide bond formation
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Solution-phase syntheses of three bioactive natural products of mixed polypeptide-polyketide biogenesis, fellutamides A, B, and C, have been achieved. Three peptide bonds are generated without the use of coupling reagents in each synthesis of the fellutamides, which act against proteasomes.
- Pirrung, Michael C.,Zhang, Fa,Ambadi, Sudhakar,Gangadhara Rao
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p. 8367 - 8375
(2016/09/09)
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- Solution phase synthetic approach to fellutamide B
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Abstract A convenient solution phase approach for the synthesis of fellutamide B with efficient purification techniques has been demonstrated on the molecule for the first time. The strategy involves the use of natural amino acids as starting materials and classical peptide coupling reactions. The synthesis has been achieved in 10 steps with overall yield of 26.7% making the synthesis facile.
- Yadav, Jhillu Singh,Dachavaram, Soma Shekar,Grée, René,Das, Saibal
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supporting information
p. 3999 - 4001
(2015/06/08)
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- Seven new and two known lipopeptides as well as five known polyketides: The activated production of silent metabolites in a marine-derived fungus by chemical mutagenesis strategy using diethyl sulphate
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AD-2-1 is an antitumor fungal mutant obtained by diethyl sulfate mutagenesis of a marine-derived Penicillium purpurogenum G59. The G59 strain originally did not produce any metabolites with antitumor activities in MTT assays using K562 cells. Tracing newly produced metabolites under guidance of MTT assay and TLC analysis by direct comparison with control G59 extract, seven new (1-7) and two known (8-9) lipopeptides were isolated together with five known polyketides 10-14 from the extract of mutant AD-2-1. Structures of the seven new compounds including their absolute configurations were determined by spectroscopic and chemical evidences and named as penicimutalides A-G (1-7). Seven known compounds were identified as fellutamide B (8), fellutamide C (9), 1.-O-methylaverantin (10), averantin (11), averufin (12), nidurufin (13), and sterigmatocystin (14). In the MTT assay, 1-14 inhibited several human cancer cell lines to varying extents. All the bioassays and HPLC-photodiode array detector (PDAD)-UV and HPLC-electron spray ionization (ESI)-MS analyses demonstrated that the production of 1-14 in the mutant AD-2-1 was caused by the activated production of silent metabolites in the original G59 fungal strain. Present results provided additional examples for effectiveness of the chemical mutagenesis strategy using diethyl sulphate mutagenesis to discover new compounds by activating silent metabolites in fungal isolates.
- Wu, Chang-Jing,Li, Chang-Wei,Cui, Cheng-Bin
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p. 1815 - 1838
(2014/06/09)
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- Total synthesis of fellutamide b and deoxy-fellutamides B, C, and D
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The total syntheses of the marine-derived lipopeptide natural product fellutamide B and deoxy-fellutamides B, C, and D are reported. These compounds were accessed through a novel solid-phase synthetic strategy using Weinreb amide-derived resin. As part of the synthesis, a new enantioselective route to (3R)-hydroxy lauric acid was developed utilizing a Brown allylation reaction followed by an oxidative cleavage-oxidation sequence as the key steps. The activity of these natural products, and natural product analogues was also assessed against Mycobacterium tuberculosis in vitro.
- Giltrap, Andrew M.,Cergol, Katie M.,Pang, Angel,Britton, Warwick J.,Payne, Richard J.
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p. 2382 - 2397
(2013/08/23)
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- Neurotrophic peptide aldehydes: Solid phase synthesis of fellutamide B and a simplified analog
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A combination of solid phase and solution phase synthetic methods have been used to complete the total synthesis of the neurotrophic lipopeptide aldehyde fellutamide B (2). The β-hydroxy aliphatic tail was prepared by regioselective reductive opening of a cyclic sulfate, and later coupled to a solid phase resin. The synthetic compound was then examined in cytotoxicity and nerve growth factor (NGF) induction assays. A simplified analog of fellutamide B also showed activity.
- Schneekloth Jr., John S.,Sanders, John L.,Hines, John,Crews, Craig M.
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p. 3855 - 3858
(2007/10/03)
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- Studies towards lipid A: a synthetic strategy for the enantioselective preparation of 3-hydroxy fatty acids
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A short and efficient enantioselective synthesis of (R)-3-hydroxydodecanoic acid is described, involving a Sharpless asymmetric dihydroxylation to produce the required (R)-stereochemistry.
- Guaragna, Annalisa,Nisco, Mauro De,Pedatella, Silvana,Palumbo, Giovanni
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p. 2839 - 2841
(2007/10/03)
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- Aminoalkyl glucosamine phosphate compounds and their use as adjuvants and immunoeffectors
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Aminoalkyl glucosamine phosphate compounds that are adjuvants and immunoeffectors are described and claimed. The compounds have a 2-deoxy-2-amino glucose in glycosidic linkage with an aminoalkyl (aglycon) group. Compounds are phosphorylated at the 4 or 6 carbon on the glucosamine ring and comprise three 3-alkanoyloxyalkanoyl residues. The compounds augment antibody production in immunized animals as well as stimulate cytokine production and activate macrophages. Methods for using the compounds as adjuvants and immunoeffectors are also disclosed.
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Page column 10
(2008/06/13)
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- Absolute configuration of aflastatin A, a specific inhibitor of aflatoxin production by Aspergillus parasiticus
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Aflastatin A (1) is a specific inhibitor of aflatoxin production by Aspergillus parasiticus. It has the novel structure of a tetramic acid derivative with a long alkyl side chain. The absolute configurations of 29 chiral centers contained in I were chemically elucidated in this study. First, four small fragment molecules were prepared from I or its methyl ether (2), and their absolute structures were assigned as N-methyl-D-alanine, (2S,4R)-2,4-dimethyl-1,6-hexanediol dibenzoate, (R)-3-hydroxydodecanoic acid, and (R)-1,2,4-butanetriol tribenzoate. Next, an acyclic fragment molecule 3 with 13 chiral centers was obtained from I by NaIO4 oxidation, and its relative stereochemistry was elucidated by J-based configuration analysis. By analyzing coupling constants of 3J(H,H) and 2,3J(C,H) and ROE data, the relative configuration of 3 was verified. Finally, by further J-based configuration analysis using a fragment molecule 7 prepared from 2 with 28 chiral carbons, all relative configurations in the alkyl side chain of I were clarified. By connecting these relative configurations with the absolute configurations of first four fragment molecules, the absolute stereochemistry of 1 was fully determined.
- Ikeda, Hiroyuki,Matsumori, Nobuaki,Ono, Makoto,Suzuki, Akinori,Isogai, Akira,Nagasawa, Hiromichi,Sakuda, Shohei
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p. 438 - 444
(2007/10/03)
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- Asymmetric Reduction of Aliphatic Short- to Long-Chain β-Keto Acids by Use of Fermenting Bakers' Yeast
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Eleven β-keto acids, ranging from 3-oxobutanoic to 3-oxooctanoic acids, were reduced with fermenting bakers' yeast to the corresponding optically active β-hydroxy acids, which were isolated as the methyl esters.In all cases, the (R)-hydroxy acids were obtained in >/=98percent ee, except for 3-oxobutanoic acid, which afforded the (S)-hydroxy acid in 86percent ee.Inhibition of fermentation was observed for 3-oxoundecanoic to 3-oxotetradecanoic acids, leading to no reduction.Lowering of the substrate concentration was found to be appreciably effective in avoiding inhibition.
- Utaka, Masanori,Watabu, Hisashi,Higashi, Hiroshi,Sakai, Takashi,Tsuboi, Sadao,Torii, Sigeru
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p. 3917 - 3921
(2007/10/02)
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- The Preparation of Optically Pure 3-Hydroxyalkanoic Acid. The Enantioface-differentiating Hydrogenation of the C=O Double Bond with Modified Raney Nickel. XXXVII
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The enantioface-differentiating hydrogenation of methyl 3-oxoalkanoate (CH3(CH2)nCOCH2COOCH3, n=0, 6, 8, 10, 12) over the (R,R)-tartaric acid-NaBr-modified Raney nickel catalyst ((R,R)-TA-NaBr-MRNi) gave methyl (R)-3-hydroxyalkanoate (CH3(CH2)nCH(OH)CH2COOCH3, n=0, 6, 8, 10, 12) in an average optical yield of 85percent.After the methyl ester had been converted to dicyclohexylammonium salt of 3-hydroxyalkanoic acid, the salt was recrystallized three times from acetonitrile and then treated with acid to give optically pure (R)-3-hydroxyalkanoic acid (CH3(CH2)nCH(OH)CH2COOH, n=0, 6, 8, 10, 12) in a reasonable yield.From the hydrogenation product with (S,S)-TA-NaBr-MRNi, optically pure (S)-3-hydroxyalkanoic acid was obtained by the same process as above.
- Nakahata, Masaaki,Imaida, Motomasa,Ozaki, Hiroshi,Harada, Tadao,Tai, Akira
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p. 2186 - 2189
(2007/10/02)
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- THE ABSOLUTE CONFIGURATION OF THE ACETYLENIC COMPOUND FALCARINDIOL
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Key Word Index-Peucedanum oreoselinum; Umbelliferae; falcarindiol; (R)-heptadecan-8-ol; (S)-heptadecan-8-ol; (3R,8S)-heptadecan-3,8-diol.Abstract-The absolute configuration of the acetylenic compound falcarindiol is established as (3R,8S) and falcarindiol is thus (+)-(3R,8S)-(Z)-heptadeca-1,9-dien-4,6-diyn-3,8-diol. (R)-Heptadecan-8-ol and (S)-heptadecan-8-ol are synthesized and (3R,8S)-heptadecan-3,8-diol is characterized.
- Lemmich, Else
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p. 1419 - 1420
(2007/10/02)
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