6036-86-8Relevant academic research and scientific papers
Enantioselective synthesis of syn-2-amino-1,3-diols via organocatalytic sequential oxa-Michael/α-amination reactions of α,β-unsaturated aldehydes
Weng, Jiang,Huang, Lin-Jie,Long, Liang,Xu, Ling-Yi,Lu, Gui
, p. 2554 - 2557 (2016)
A general and efficient method for the enantioselective synthesis of syn-2-amino-1,3-diols is reported. It involves the methodology of secondary amine-catalyzed one-pot sequential oxa-Michael/α-amination reactions of α,β-unsaturated aldehydes. This method has also been successfully applied to highly efficient total syntheses of (+)-safingol and d-threo-clavaminol H with excellent stereoselectivities.
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.
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.]
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.
A general synthesis of sphinganines through multicomponent catalytic asymmetric aziridination
Mukherjee, Munmun,Zhou, Yubai,Gupta, Anil K.,Guan, Yong,Wulff, William D.
supporting information, p. 1386 - 1390 (2014/03/21)
A catalytic asymmetric synthesis of all four stereoisomers of sphinganine is described starting from hexadecanal. Utilizing either the (R) or (S) enantiomer of a BOROX catalyst, a multicomponent reaction of this aldehyde with an amine and ethyl diazoacetate gives rise to enantiomeric aziridine-2- carboxylates. Access to all diastereomers of sphinganine is realized upon ring opening of the enantiopure aziridine-2-carboxylate at the C-3 position by direct SN2 attack of an oxygen nucleophile, which occurs with inversion of configuration and by ring expansion of an N-acyl aziridine to an oxazolidinone and then hydrolysis. Overall, this process results in the formal ring opening of the aziridine with an oxygen nucleophile with retention of configuration. The synthesis of all four stereoisomers of sphinganine was achieved by multi-component asymmetric aziridination of hexadecanal. Complete stereocontrol is realized with the proper choice of the chirality of the BOROX catalyst and the introduction of an oxygen substituent at the 3-position of the aziridine with either retention or inversion. MEDAM = tetramethyldianisylmethyl. Copyright
A General Synthesis of Sphinganines through Multicomponent Catalytic Asymmetric Aziridination
Mukherjee, Munmun,Zhou, Yubai,Gupta, Anil K.,Guan, Yong,Wulff, William D.
supporting information, p. 1386 - 1390 (2015/10/05)
A catalytic asymmetric synthesis of all four stereoisomers of sphinganine is described starting from hexadecanal. Utilizing either the (R) or (S) enantiomer of a BOROX catalyst, a multicomponent reaction of this aldehyde with an amine and ethyl diazoacetate gives rise to enantiomeric aziridine-2-carboxylates. Access to all diastereomers of sphinganine is realized upon ring opening of the enantiopure aziridine-2-carboxylate at the C-3 position by direct SN2 attack of an oxygen nucleophile, which occurs with inversion of configuration and by ring expansion of an N-acyl aziridine to an oxazolidinone and then hydrolysis. Overall, this process results in the formal ring opening of the aziridine with an oxygen nucleophile with retention of configuration.
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.
