3102-56-5Relevant academic research and scientific papers
Convergent evolution of bacterial ceramide synthesis
Ashley, Ben,Campopiano, Dominic J.,Chamberlain, Joshua D.,Coleman, Aimiyah,D’Emilia, Rachel,Fu, Larina,Guan, Ziqiang,Hansen, Matthew E. B.,Klein, Eric A.,Mohan, Eric C.,Nguyen, Hung,Stankeviciute, Gabriele,Tang, Peijun
, (2022/01/06)
The bacterial domain produces numerous types of sphingolipids with various physiological functions. In the human microbiome, commensal and pathogenic bacteria use these lipids to modulate the host inflammatory system. Despite their growing importance, their biosynthetic pathway remains undefined since several key eukaryotic ceramide synthesis enzymes have no bacterial homolog. Here we used genomic and biochemical approaches to identify six proteins comprising the complete pathway for bacterial ceramide synthesis. Bioinformatic analyses revealed the widespread potential for bacterial ceramide synthesis leading to our discovery of a Gram-positive species that produces ceramides. Biochemical evidence demonstrated that the bacterial pathway operates in a different order from that in eukaryotes. Furthermore, phylogenetic analyses support the hypothesis that the bacterial and eukaryotic ceramide pathways evolved independently. [Figure not available: see fulltext.]
Short asymmetric syntheses of sphinganine [(2S,3R)-2-aminooctadecane-1,3-diol] and its C(2)-epimer
Da Silva Pinto, Solange,Davies, Stephen G.,Fletcher, Ai M.,Newton, Sophie K.,Roberts, Paul M.,Thomson, James E.
supporting information, (2021/02/09)
A short asymmetric synthesis of sphinganine [(2S,3R)-2-aminooctadecane-1,3-diol] and its C(2)-epimer is reported. The synthesis of sphinganine employs diastereoselective aminohydroxylation of tert-butyl 2-octadecenoate [conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide, then in situ enolate oxidation with (+)-camphorsulfonyloxaziridine (CSO)] and a stereospecific rearrangement of the resultant anti-α-hydroxy-β-amino ester into the corresponding anti-α-amino-β-hydroxy ester. Final hydrogenolysis and ester reduction completes the synthesis of the sphingoid base target. The synthesis of the C(2)-epimer follows a similar route, incorporating a diastereoselective reduction protocol to transform the anti-α-hydroxy-β-amino ester into its syn-α-hydroxy-β-amino ester counterpart.
Development of Asymmetric Transfer Hydrogenation with a Bifunctional Oxo-Tethered Ruthenium Catalyst in Flow for the Synthesis of a Ceramide (D-erythro-CER[NDS])
Touge, Taichiro,Kuwana, Masahiro,Komatsuki, Yasuhiro,Tanaka, Shigeru,Nara, Hideki,Matsumura, Kazuhiko,Sayo, Noboru,Kashibuchi, Yoshinobu,Saito, Takao
supporting information, p. 452 - 461 (2019/01/04)
The development of an efficient synthetic route for an optically active ceramide compound (d-erythro-CER[NDS]) is described. The route proceeds through asymmetric transfer hydrogenation in a pipes-in-series flow reactor with oxo-tethered ruthenium complex-catalyzed dynamic kinetic resolution. This synthesis was accomplished without any expensive reagents, and none of the intermediates required isolation. This resulted in a robust process that has been successfully run on a production scale.
Multicomponent cis- and trans-Aziridinatons in the Syntheses of All Four Stereoisomers of Sphinganine
Zhou, Yubai,Mukherjee, Munmun,Gupta, Anil K.,Wulff, William D.
, p. 2230 - 2233 (2017/05/12)
All four stereoisomers of sphinganine can be synthesized by a multicomponent aziridination of an aldehyde, an amine and an α-diazo carbonyl compound mediated by a BOROX catalyst with high asymmetric induction (≥96% ee). The threo isomers are available from ring-opening of cis-aziridines by an oxygen nucleophile with inversion at the C-3 position and the erythro-isomers are likewise available from trans-aziridines.
'Chiron' approach to stereoselective synthesis of sphinganine and unnatural safingol, an antineoplastic and antipsoriatic agent
Das, Pintu,Kundooru, Somireddy,Shaw, Arun K.
, p. 14505 - 14511 (2016/02/19)
Highly stereoselective total syntheses of sphingoid bases, natural bioactive ceramide sphinganine 1 (with an overall yield of 33%) and unnatural antineoplastic and antipsoriatic drug safingol 17 (with an overall yield of 38%) starting from chirons 3,4,6-tri-O-benzyl-d-galactal and 3,4,6-tri-O-benzyl-d-glucal respectively have been demonstrated. Mitsunobu reaction and late stage olefin cross metathesis are utilized as important steps in order to complete the total synthesis of these sphingoid molecules.
Synthesis and identification of unprecedented selective inhibitors of CK1ε
Silveira-Dorta, Gastón,Sousa, Inês J.,Fernandes, Miguel X.,Martín, Victor S.,Padrón, José M.
, p. 308 - 317 (2015/04/27)
A small and structure-biased library of enantiopure anti-β-amino alcohols was prepared in a straightforward manner by a simplified version of the Reetz protocol. Antiproliferative activity testing against a panel of five human solid tumor cell lines gave GI50 values in the range 1-20 μM. The reverse screening by computational methods against 58 proteins involved in cancer pointed to kinases as possible therapeutic target candidates. The experimental determination of the interaction with 456 kinases indicated that the compounds behave as selective CK1ε inhibitors. Our results demonstrate that the lead compound represents the first selective CK1ε inhibitor with proven antiproliferative activity in cancer cell lines.
Pd-catalyzed intramolecular aminohydroxylation of alkenes with hydrogen peroxide as oxidant and water as nucleophile
Zhu, Haitao,Chen, Pinhong,Liu, Guosheng
supporting information, p. 1766 - 1769 (2014/03/21)
A palladium-catalyzed intramolecular aminohydroxylation of alkenes was developed, in which H2O2 was applied as the sole oxidant. A variety of related alkyl alcohols could be successfully obtained with good yields and excellent diastereoselectivities, which directly derived from oxidation cleavage of alkyl C-Pd bond by H2O2. Facile transformation of these products provided a powerful tool toward the synthesis of 2-amino-1,3-diols and 3-ol amino acids. Preliminary mechanistic studies revealed that major nucleophilic attack of water (SN2 type) at high-valent Pd center contributes to the final C-O(H) bond formation.
Direct stereoselective synthesis of enantiomerically pure anti -β-amino alcohols
Silveira-Dorta, Gastón,Donadel, Osvaldo J.,Martín, Víctor S.,Padrón, José M.
, p. 6775 - 6782 (2014/08/18)
Enantiomerically pure anti-β-amino alcohols were synthesized from optically pure α-(N,N-dibenzylamino)benzyl esters, derived from α-amino acids, by the sequential reduction to aldehyde with DIBAL-H at -78 °C and subsequent in situ addition of Grignard reagents. Besides anti-β-amino alcohols, anti-2-amino-1,3-diols and anti-3-amino-1,4-diols were obtained in good yields (60-95%) and excellent stereoselectivity (de > 95%). Our technique is compatible with free hydroxyl groups present in the substrate. To demonstrate the versatility of the method, spisulosine and sphinganine were synthesized in two steps from the appropriate N,N-dibenzyl-l-aminobenzyl ester in 42% and 45% yield, respectively.
Synthesis of D-erythro-sphinganine through serine-derived α-amino epoxides
Siciliano, Carlo,Barattucci, Anna,Bonaccorsi, Paola,Di Gioia, Maria Luisa,Leggio, Antonella,Minuti, Lucio,Romio, Emanuela,Temperini, Andrea
, p. 5320 - 5326 (2014/06/23)
A total synthesis of d-erythro-sphinganine [(2S,3R)-2-aminooctadecane-1,3- diol] starting from commercial N-tert-butyloxycarbonyl-l-serine methyl ester is described. The approach is based on the completely stereoselective preparation of an α-amino epoxide obtained by treating a protected l-serinal derivative with dimethylsulfoxonium methylide. The oxirane synthon is obtained with an anti configuration fitting the (2S,3R) stereochemistry of the 2-amino-1,3-diol polar head of d-erythro-sphinganine. The synthetic procedure afforded the target compound in a 68% overall yield based on the initial amount of the starting l-serine material.
METHOD FOR PRODUCING HIGH-PURITY CERAMIDE
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Paragraph 0050, (2014/11/13)
Provided is a method for producing an optically active ceramide by an N-acylation (amidation) reaction of an optically active aminodiol, wherein a crude ceramide produced therein is purified by an industrially advantageous process. Namely, provided is a method for producing a high-purity ceramide that has high diastereo purity with high yield. A high-purity ceramide is produced by: a step wherein a ceramide represented by general formula (1) is produced by reacting an aminodiol with an alkyl ester having 1-5 carbon atoms of an aliphatic carboxylic acid having 12-24 carbon atoms, said aliphatic carboxylic acid optionally having a hydroxyl group, in a hydrocarbon solvent having 5-10 carbon atoms; and a step wherein an alcohol having 1-3 carbon atoms is added into the reaction mixture obtained in the preceding step, thereby causing crystals to precipitate. (In the formula, R1 represents an alkyl group which has 13-17 carbon atoms and optionally has a carbon-carbon unsaturated bond; R2 represents an alkyl group which has 11-23 carbon atoms and optionally has a hydroxyl group; and * represents an optically active state.)
